MINI REVIEW
Lub outpost tawm tsam mob qog noj ntshav: universal cancer tsuas yog cov cim
Chengchen Qian 1, Xiaolong Zou 2, Wei Li 1, 3, Yinshan Li4, Wenqiang Yu 5
1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, Suav teb;2 Department of General Surgery, Thawj Tsev Kho Mob ntawm Harbin Medical University, Harbin 150001, Tuam Tshoj;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, Tuam Tshoj;4 Tib neeg lub tsev kho mob ntawm Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750002, Tuam Tshoj;5Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
TSAB NTAWV
Cancer yog qhov ua rau tuag thoob ntiaj teb.Kev kuaj mob ntxov ntxov tuaj yeem txo qis kev tuag ntawm txhua hom mob qog noj ntshav;Txawm li cas los xij, kev tshawb pom ntxov biomarkers tsis muaj rau feem ntau ntawm cov qog nqaij hlav.DNA methylation yeej ib txwm yog lub hom phiaj tseem ceeb ntawm kev txaus siab vim DNA methylation feem ntau tshwm sim ua ntej lwm yam kev hloov pauv caj ces.Thaum tshawb xyuas cov yam ntxwv ntawm mob qog noj ntshav siv cov lus qhia tshiab qhia qhov sib luag rau DNA methylation, cov kab mob qog noj ntshav thoob ntiaj teb tsuas yog cov cim (UCOMs) tau tshwm sim los ua cov neeg sib tw muaj zog rau kev ua tau zoo thiab raug kuaj pom mob qog noj ntshav thaum ntxov.Thaum cov nqi kho mob ntawm cov qog nqaij hlav qog noj ntshav tam sim no ploj zuj zus los ntawm qhov tsis tshua muaj siab thiab / lossis qhov tshwj xeeb tsawg, cov yam ntxwv tshwj xeeb ntawm UCOMs ua kom muaj txiaj ntsig zoo hauv kev kho mob.Kev lees paub ntawm qhov chaw kho mob muaj peev xwm ntawm UCOMs hauv ntsws, ncauj tsev menyuam, endometrial, thiab urothelial cancers ntxiv txhawb kev siv UCOMs hauv ntau hom mob qog noj ntshav thiab ntau yam xwm txheej kho mob.Qhov tseeb, cov ntawv thov ntawm UCOMs yog tam sim no nyob rau hauv kev tshawb nrhiav ntxiv nrog kev ntsuam xyuas ntxiv hauv kev tshawb pom ntxov ntawm mob qog noj ntshav, pab kuaj mob, kev kho mob zoo, thiab kev saib xyuas rov qab.Cov txheej txheem molecular uas UCOMs kuaj mob qog noj ntshav yog cov ntsiab lus tseem ceeb tom ntej uas yuav tsum tau soj ntsuam.Daim ntawv thov ntawm UCOMs hauv qhov xwm txheej tiag tiag kuj yuav tsum tau siv thiab kho kom zoo.
KEYWORDS
Kev kuaj mob qog noj ntshav;kuaj mob qog noj ntshav;DNA methylation;mob qog noj ntshav epigenetics;mob qog noj ntshav biomarkers
Vim li cas peb thiaj li xav tau tshiab biomarkers?
Tom qab tawm tsam mob qog noj ntshav rau ntau tshaj li ib puas xyoo, mob qog noj ntshav tseem yog qhov ua rau muaj kev phom sij loj tshaj plaws rau noob neej.Mob qog noj ntshav tseem muaj kev txhawj xeeb txog kev noj qab haus huv thoob ntiaj teb nrog 19.3 lab tus neeg mob tshiab thiab ze li 10 lab tus neeg tuag kwv yees xyoo 20201. Hauv 2020 kwv yees li 4.6 lab tus neeg mob qog noj ntshav tshiab tau kuaj pom hauv Suav teb, suav txog 23.7% ntawm cov mob qog noj ntshav tshiab thoob ntiaj teb raws li GLOBOCAN1.Tsis tas li ntawd, kwv yees li 3 lab tus neeg tuag tau raug suav tias yog mob qog noj ntshav hauv Suav teb xyoo 2020, uas yog 30% ntawm cov neeg mob qog noj ntshav thoob ntiaj teb tuag1.Cov ntaub ntawv txheeb xyuas no tau qhia tias Tuam Tshoj yog thawj qhov kev tshwm sim thiab kev tuag ntawm tus mob qog noj ntshav.Ntxiv mus, 5-xyoo kev mob qog noj ntshav muaj sia nyob yog 40.5%, uas yog 1.5 npaug qis dua li 5-xyoo txoj sia nyob hauv Tebchaws Meskas 2,3.Qhov kev sib piv qis qis thiab cov neeg tuag ntau dua hauv Suav teb dua li hauv cov teb chaws uas muaj kev loj hlob ntawm tib neeg siab dua qhia tias kev tiv thaiv kab mob qog noj ntshav thiab kev soj ntsuam tau zoo thiab raug nqi yog qhov xav tau sai.Kev tshawb pom ntxov ntawm mob qog noj ntshav yog ib qho tseem ceeb tshaj plaws hauv kev kho mob.Kev tshawb pom ntxov ntawm mob qog noj ntshav tuaj yeem txhim kho qhov kev cia siab thiab kev muaj sia nyob thaum ntxov ntawm yuav luag txhua hom mob qog noj ntshav 4.Cov tswv yim kev tshuaj ntsuam tau ua tiav tau ua rau muaj kev poob qis hauv qhov tshwm sim thiab kev tuag ntawm ncauj tsev menyuam, lub mis, mob plab, thiab mob qog nqaij hlav prostate.
Txawm li cas los xij, txhawm rau txhawm rau txhawm rau txhawm rau txhawm rau kuaj mob qog noj ntshav, tsis yog ib txoj haujlwm yooj yim.Kev tshawb xyuas txog kev mob qog noj ntshav thiab kev mob qog noj ntshav thaum ntxov, txheeb xyuas thiab txheeb xyuas qhov tseeb ntawm kev tshawb pom bio-markers, thiab tsim cov cuab yeej siv tau yooj yim thiab muaj tseeb thaum ntxov tau ib txwm yog qhov teeb meem loj tshaj plaws hauv cov txheej txheem 4.Kev kuaj pom tseeb ntawm mob qog noj ntshav tuaj yeem paub qhov txawv ntawm cov kab mob malignant, uas yuav pab kom tsis txhob muaj cov txheej txheem tsis tsim nyog thiab pab tswj cov kab mob ntxiv.Cov tswv yim tshawb pom ntxov tam sim no suav nrog endoscope-based biopsies, kuaj pom kev kho mob, cytology, immunoassays, thiab biomarker tests5-7.Ua intrusive thiab kim, endoscope-raws li biopsies nqa ib lub nra hnyav uas yog ib txoj kev kho mob loj uas vam khom rau cov neeg ua haujlwm.Zoo li cytology, ob txoj kev tshuaj ntsuam yog nyob ntawm cov kws kho mob thiab ua raws li kev txiav txim siab ntawm tus kheej nrog kev ua tau zoo uas nyob deb ntawm qhov zoo tshaj 8.Nyob rau hauv sib piv, immunoassays yog heev tsis raug, muab qhov siab tsis tseeb-zoo tus nqi.Kev kuaj pom kev kho mob, raws li kev tshuaj ntsuam xyuas, yuav tsum tau siv cov cuab yeej kim thiab cov kws tshaj lij tshwj xeeb.Yog li ntawd, kev kuaj pom kev kho mob tsis tshua muaj kev txwv vim muaj kev nkag tau tsawg.Rau tag nrho cov laj thawj no, biomarkers zoo li yog qhov kev xaiv zoo dua rau kev kuaj pom mob qog noj ntshav thaum ntxov.
Kev xa mus rau: Yinshan Li thiab Wenqiang Yu
Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn
ORCID ID: https://orcid.org/0009-0005-3340-6802 thiab
https://orcid.org/0000-0001-9920-1133
Tau txais Lub Yim Hli 22, 2023;tau txais Lub Kaum Hli 12, 2023;
luam tawm online Lub Kaum Ib Hlis 28, 2023.
Muaj nyob ntawm www.cancerbiomed.org
© 2023 Cancer Biology & Tshuaj.Creative Commons
Attribution-NonCommercial 4.0 Daim ntawv tso cai thoob ntiaj teb
Biomarkers tam sim no tau muab faib ua cov proteins, DNA hloov pauv cov cim, cov cim epigenetic, chromosomal abnormalities, RNA cov cim tau ncaj qha los ntawm cov qog, lossis cov qog nqaij hlav tau txais kev ncaj qha los ntawm lub cev.Protein markers yog cov feem ntau siv biomarkers hauv kev kuaj mob qog noj ntshav thiab kuaj mob.Protein biomarkers, raws li kev tshuaj ntsuam bio-markers, raug txwv los ntawm kev nyiam cuam tshuam los ntawm cov kab mob benign, uas ua rau muaj kev kuaj mob ntau dhau thiab kev kho mob ntau dhau, raws li tau tshaj tawm rau α-fetoprotein thiab prostate-specific antigen (PSA) 9,10.RNA cov cim muaj xws li cov qauv kev qhia caj ces thiab lwm yam tsis-coding RNA cov cim.Ib qho kev sib txuas ntawm cov caj ces RNA cov cim tuaj yeem tshawb pom siv cov qauv tso zis, qhov rhiab heev ntawm qhov tsis txaus siab (60%) rau cov qog thawj, thiab kev tshawb nrhiav uas tuaj yeem cuam tshuam los ntawm qhov yooj yim degradation ntawm RNA nyob rau hauv normalenviron-ment11.Cov cim caj ces thiab epigenetic ob qho tib si ntsib teeb meem ntawm kev nthuav dav hauv cov qog thiab kev txwv rau hom mob qog noj ntshav.
DNA methylation tau ua ib tus neeg sib tw muaj zog raws li kev tshawb pom ntxov biomarker txij li thawj zaug txuas rau mob qog noj ntshav los ntawm Feinberg hauv xyoo 198312. DNA methylation aberrations raug pom nyob rau hauv txhua theem ntawm mob qog noj ntshav, thaum ntxov li precancerous theem.Aberrant DNA hypermethylation feem ntau tshwm sim ntawm CpG Islands hauv cov noob caj noob ces los tiv thaiv qog nqaij hlav 13,14.Cov kev tshawb fawb kuj tau qhia tias qhov txawv txav DNA hypermethylation koom nrog kev txhim kho ntawm kev tsim kho-opmental regulators15.DNA methylation hav, uas feem ntau cuam tshuam nrog kev txhim kho kev tswj hwm thiab cov qog nqaij hlav hypermethylated, tuaj yeem hloov cov noob qhia hom mus rau hom DNA methylation-nyob ruaj khov dua thiab txo qhov kev sib txuas rau methylated histone H3K27me3 thiab cuam tshuam polycomb proteins16,17.
Ntawm cov neeg coob ntawm cov ntawv luam tawm DNA methylation cov cim, ob peb tau ua tiav hauv kev ua lag luam;Txawm li cas los xij, tam sim no kev lag luam DNA methylation cov cim thiab cov tshuaj ntsuam xyuas tseem tsis tau qhib tag nrho lub peev xwm ntawm kev kuaj pom mob qog noj ntshav thaum ntxov rau ntau yam laj thawj18.Txawm hais tias feem ntau ua tau zoo siv cov ntaub ntawv database, cov biomarkers feem ntau ua tsis tau zoo hauv lub ntiaj teb tiag tiag vim qhov tseeb tias cov qauv hauv ntiaj teb no feem ntau nyuaj thiab tsis yog tus sawv cev raws li cov neeg xaiv hauv cov ntaub ntawv.Tom ntej no-tiam-sequencing-based multi-cancer methylation thaum ntxov tshawb pom tau pom tias tsuas muaj 16.8% thiab 40.4% rhiab nyob rau theem I thiab II mob qog noj ntshav, raws li 19.Kev kuaj xyuas thaum ntxov yuav tsum muaj kev ruaj ntseg ntau dua thiab muaj tseeb biomarkers.
Universal cancer nkaus xwb marker (UCOM) nrhiav tau siv cov lus qhia muab tso ua ke (GPS)
Txawm hais tias muaj ntau xyoo ntawm kev tshawb fawb txog kev mob qog noj ntshav, kev tiv thaiv thiab kev kho mob txaus siab tsis tau ua tiav.Cov txheej txheem tshiab yog xav tau los pab cov kws tshawb fawb kom ntsuas mob qog noj ntshav kom zoo.Nyob rau hauv 23 lub xyoos dhau los, 6 cov cim mob qog noj ntshav, xws li evad-ing apoptosis, cov ntaub so ntswg ntxeem tau & metastasis, thiab lwm yam, tau nthuav dav mus rau 14 los ntawm kev suav nrog cov yam ntxwv zoo li nonmutational epi-genetic reprogramming thiab polymorphic microbiomes20,21.Raws li cov ntsiab lus ntxiv hais txog kev mob qog noj ntshav tau nthuav tawm, ntau qhov kev xav tau nkag mus rau hauv kev tshawb fawb txog mob qog noj ntshav.Kev tshawb nrhiav mob qog noj ntshav tau maj mam tuaj rau hauv ib qho tshiab hauv ob qho kev qhia (kev sib koom ua ke thiab tus kheej).Nrog rau txoj kev loj hlob ntawm precision oncol-ogy nyob rau hauv xyoo tas los no, lub hom phiaj ntawm kev tshawb fawb mob qog noj ntshav yog leaning rau tus kheej lub hom phiaj kev kho mob thiab cov heterogeneity ntawm cancer22.Yog li, tsis ntev los no tau txheeb xyuas cov kab mob qog noj ntshav tau tsom feem ntau ntawm cov qog nqaij hlav tshwj xeeb, xws li PAX6 forcer-vical cancer23 thiab BMP3 rau mob qog noj ntshav 24.Kev ua tau zoo ntawm cov biomarkers tshwj xeeb rau hom mob qog noj ntshav txawv, tab sis nws tseem tsis tuaj yeem ua rau cov tib neeg raug mob los kuaj xyuas tag nrho cov qog nqaij hlav ib txhij vim muaj kev txwv ntawm kev kis tus kab mob lom thiab tus nqi siab.Nws yuav yog qhov zoo tshaj yog tias peb tuaj yeem txheeb xyuas ib qho, muaj zog biomarker uas muaj txiaj ntsig zoo rau txhua hom mob qog noj ntshav thaum ntxov.
Txhawm rau ua tiav lub hom phiaj zoo tshaj plaws, tus neeg sib tw biomarker zoo dua yuav tsum raug xaiv los ntawm cov npe ntawm hom biomarker muaj peev xwm.DNA methylation aberrations, ntawm tag nrho cov caj ces thiab epige-netic profiles, paub tias muaj feem xyuam rau mob qog noj ntshav thiab yog qee qhov ntxov tshaj plaws, yog tias tsis yog thawj zaug, kev mob qog noj ntshav yuav tshwm sim raws sijhawm.Kev tshawb nrhiav DNA methylation pib ntxov, tab sis tau cuam tshuam los ntawm qhov tsis muaj kev tshawb fawb.Ntawm 28 lab qhov muaj peev xwm methylated CpG qhov chaw hauv genome, tus lej tswj tau yuav tsum raug kuaj xyuas thiab ua raws li cov genome kom nkag siab zoo dua cov qog nqaij hlav.Tag nrho cov genome bisulfite sequencing (WGBS), uas tau pom zoo los ua tus qauv kub ntawm DNA methylation sequencing, tsuas tuaj yeem npog 50% ntawm Cs hauv cov qog nqaij hlav cancer vim qhov kev kho bisulfite uas ua rau DNA tawg thiab txo cov genome complexity thaum lub sij hawm. Convert Cs to Ts25.Lwm txoj kev, xws li 450k chips, tsuas yog npog 1.6% ntawm genome methylation.Raws li 450k cov ntaub ntawv, lub vaj huam sib luag DNA methylation kuaj pom muaj 35.4% rhiab heev rau 6 hom mob qog noj ntshav 26.Cov kev txwv ntawm hom mob qog noj ntshav, kev ua haujlwm tsis zoo, thiab lub suab nrov tsim los ntawm cov txheej txheem tshawb nrhiav hauv cov txheej txheem tshuaj ntsuam tau dhau los ua qhov teeb meem loj tshaj plaws rau kev kuaj mob pan-cancer.
Txhawm rau tshawb xyuas cov qauv epigenetic zoo dua ntawm cov hlwb thaum lub sij hawm tumorigenesis thiab metastasis, peb tau tsim ib qho GPS tshwj xeeb rau genome-wide DNA methylation detection, uas npog txog 96% ntawm CpG qhov chaw hauv 0.4 billion nyeem 25.GPS yog ib txoj kev sib tw bilateral siv 3′ kawg ntawm DNA ntu ntawm cov tsis hloov pauv methyl-cytosine tom qab kev kho bisulfite uas coj cov kev sib raug zoo ntawm DNA methylation suav ntawm 5′ kawg los ntawm kev sib tw kawg (Daim duab 1) 25.Cov methyl-cytosine guiding strand, ua raws li cov qauv strand, pab nyob rau hauv high-GC cheeb tsam kev sib raug zoo uas rov qab tau cov ntaub ntawv feem ntau tso tseg sequencing hauv ib txwm WGBS.Lub hnub nyoog npog siab ntawm GPS muab ntau cov ntaub ntawv DNA methylation, uas tso cai rau peb los tshuaj xyuas cov kab mob qog noj ntshav nrog kev daws teeb meem ntau dua hauv cov cheeb tsam uas tsis tau tshawb xyuas yav dhau los.
GPS muab peb lub cuab yeej muaj zog los tshawb xyuas qhov sib xws ntawm kev mob qog noj ntshav, uas tuaj yeem ua kom yooj yim rau kev tshawb fawb txog qog noj ntshav thiab muaj peev xwm nrhiav tau cov lus piav qhia thoob ntiaj teb rau qog nqaij hlav thiab metastasis.Thaum soj ntsuam GPS cov ntaub ntawv ntawm cov kab mob qog noj ntshav, ib qho tshwm sim tshwj xeeb tau ntsib ntau zaus.Muaj ntau thaj chaw uas tau tshwm sim los ntawm qhov tsis zoo-mally hypermethylated hauv ntau hom qog nqaij hlav.Qhov kev nrhiav pom tsis tau pom tau tom qab tau lees paub los ua UCOMs.Ntau dua 7,000 cov qauv los ntawm 17 hom mob qog noj ntshav hauv Cancer Genome Atlas (TCGA) cov ntaub ntawv tau txheeb xyuas, cov uas peb txheeb xyuas thawj UCOM, HIST1H4F, cov noob caj noob ces uas yog hypermethylated hauv txhua hom mob qog noj ntshav27.Ib qho ntawm UCOMs tau pom thiab siv tau hauv TCGA database, Gene Expression Omnibus (GEO) database, thiab cov qauv kuaj mob tiag tiag.Txog tam sim no, HIST1H4F, PCDHGB7, thiab SIX6 tau pom thiab siv tau raws li UCOMs.Qhov kev tshawb pom tsis txaus ntseeg ntawm UCOMs muab cov lus teb muaj zog rau qhov xav tau rau kev kuaj pom mob qog noj ntshav sai.UCOMs muab kev daws teeb meem rau ib qho kev kuaj pom ntawm ntau yam qog noj ntshav.
Cov yam ntxwv ntawm UCOMs
Thaum muaj kev lees paub, UCOMs tau pom tias muaj plaub yam tseem ceeb uas ua rau UCOMs dhau qhov kev ua tau zoo ntawm biomarkers tam sim no (Daim duab 2).
Tshwj xeeb rau malignancy
UCOMs yog tshwj xeeb rau cov qog nqaij hlav los yog ua ntej mob qog noj ntshav thiab tsis cuam tshuam los ntawm kev hloov pauv ntawm lub cev.Qee cov cim qhia txog mob qog noj ntshav tam sim no uas tau siv dav hauv kev tshawb pom ntxov thiab / lossis kev tshuaj ntsuam xyuas tau ua rau muaj kev kuaj mob ntau dhau.Kev nce qib PSA, cov cuab yeej tshuaj ntsuam xyuas tau lees paub, kuj tau kuaj pom hauv cov xwm txheej zoo, xws li prostate hyperplasia thiab prostatitis10.Kev kuaj mob ntau dhau thiab ua rau muaj kev kho mob ntau dhau ua rau txo qis ntawm lub neej vim kev mob plab, tso zis, thiab muaj teeb meem kev sib deev28.Lwm cov protein-based thiab dav siv biomarkers nyob rau hauv qhov chaw kho mob, xws li CA-125, tsis muaj txiaj ntsig zoo thaum ua rau muaj kev kuaj mob ntau dhau thiab kev kho mob ntau dhau29.Qhov tshwj xeeb siab ntawm UCOMs rau malignancies zam cov luv luv no.Lub UCOM, PCDHGB7, muaj txiaj ntsig zoo qhov txawv ntawm qib siab squamous intraepithelial lesions (HSILs) thiab mob qog noj ntshav ntawm lub ncauj tsev menyuam los ntawm cov qauv ib txwm thiab qib qis squamous intraepithelial lesions (LSILs), thaum feem ntau lwm cov bio-markers tsuas tuaj yeem sib txawv qog noj ntshav los ntawm cov qauv 30.Txawm hais tias PCDHGB7 tsis pom qhov sib txawv tseem ceeb ntawm ib txwm endometrium thiab endometrial hyperplasia, qhov sib txawv tseem ceeb tau kuaj pom ntawm ib txwm endometrium thiab atypical hyperplasia, thiab txawm tias qhov sib txawv ntau dua tau kuaj pom ntawm ib txwm endometrium thiab endometrial cancer (EC) raws li PCDHGB731.UCOMs yog qhov tshwj xeeb rau cov kab mob qog nqaij hlav hauv cov ntaub ntawv thiab cov qauv kuaj mob.Los ntawm tus neeg mob qhov kev xav, tshwj xeeb UCOMs txo qhov pib rau kev nkag siab cov ntsiab lus nyuaj ntawm ntau yam kev ua haujlwm tsis zoo ntawm biomarkers thiab cov kev ntxhov siab sib xws thaum lub sij hawm ntsuam xyuas.Los ntawm cov kws kho mob txoj kev xav, UCOMs tshwj xeeb sib txawv ntawm cov kab mob benign, uas pab rau cov neeg mob triage thiab txo cov txheej txheem kho mob tsis tsim nyog thiab kev kho mob ntau dhau.Yog li ntawd, UCOMs tshwj xeeb txo qis kev kho mob rov ua dua tshiab, txo kev ntxhov siab hauv lub cev, thiab ua kom muaj kev kho mob ntau ntxiv rau cov neeg xav tau.
Daim duab 1 Schematic ntawm GPS workflow rau DNA methylation detection25.Grey kab: nkag mus DNA ib ntus;kab liab: DNA kho nrog T4 DNA polymerase, hloov cytosine nrog 5′-methylcytosine ntawm 3′ kawg ntawm cov tswv yim;xiav C nrog Kuv: methylated cytosine;xiav C: unmethylated cytosine;daj T: thymine25.
Tag nrho los yog tsis muaj dab tsi
UCOMs tsuas muaj nyob rau hauv cov qog nqaij hlav cancer thiab kuaj pom nyob rau hauv yuav luag tag nrho cov qog nqaij hlav cancer.HIST1H4F tau lees paub tias yog hypermethylated nyob rau hauv yuav luag txhua hom qog nqaij hlav tab sis tsis nyob hauv cov qauv ib txwm27.Ib yam li ntawd, PCDHGB7 thiab SIX6 kuj tau pom tias yog hypermethylated nyob rau hauv tag nrho cov qog nqaij hlav tab sis tsis nyob rau hauv ib txwm kuaj 30-32.Cov yam ntxwv tshwj xeeb no txhim kho kev ua tau zoo ntawm UCOMs nrog rau kev txwv ntawm kev tshawb pom thiab rhiab heev.Tsawg li 2% ntawm cov qog nqaij hlav qog noj ntshav tuaj yeem sib txawv hauv cov qauv, ua rau UCOMs muaj txiaj ntsig biomarker ntau dua li cov biomarkers uas twb muaj lawm feem ntau30.Raws li biomarker siv rau kev kuaj mob qog nqaij hlav hauv plab, KRAS kev hloov pauv tsuas yog muaj nyob hauv kwv yees li 36% ntawm cov neeg mob qog noj ntshav, qhia-kev kuaj mob tsis zoo33.Qhov qis dua ntawm KRAS kev hloov pauv hauv cov qog nqaij hlav hauv plab txwv KRAS nrog rau lwm cov biomarkers.Qhov tseeb, kev sib xyaw ua ke ntawm biomarkers yuav zoo li cog lus thaum pib, tab sis tsis yog ib txwm ua kom muaj txiaj ntsig zoo thaum ua kom pom ntau lub suab nrov hauv kev tshawb nrhiav thiab feem ntau cuam tshuam nrog cov txheej txheem kev sim nyuaj.Hauv qhov sib piv, PCDHGB7 thiab lwm yam UCOMs muaj nyob rau hauv txhua yam mob qog noj ntshav.UCOMs tshawb pom cov qog nqaij hlav qog nqaij hlav hauv ntau hom kab mob qog noj ntshav nrog qhov tseeb tshaj plaws thaum tshem tawm cov txheej txheem kev soj ntsuam cov suab nrov nrov.Nws tsis yooj yim rau kev kuaj mob qog noj ntshav hauv cov qauv ntau, tab sis nws yog qhov nyuaj heev los kuaj mob qog noj ntshav hauv cov qauv me me.UCOMs muaj peev xwm txheeb xyuas cov qog nqaij hlav me me.
Daim duab 2 Cov yam ntxwv ntawm UCOMs.
Kev kuaj mob qog noj ntshav ua ntej hloov pauv pathological
UCOMs tuaj yeem kuaj pom nyob rau theem ua ntej mob qog noj ntshav ua ntej kev hloov pauv pathological.Raws li epigenetic biomarkers, UCOM abnormalities tshwm sim nyob rau hauv ib tug ua ntej theem tshaj phenotypic abnormalities thiab ntes tau nyob rau hauv lub qog nqaij hlav, kev loj hlob, thiab metastasis34,35.Lub rhiab heev ntawm UCOM lub sijhawm dhau los txhim kho UCOM kev ua tau zoo hauv kev kuaj pom mob qog noj ntshav thaum ntxov thiab ua ntej mob qog noj ntshav.Kev kuaj mob qog noj ntshav thaum ntxov raws li biopsies thiab cytology tuaj yeem nyuaj rau cov kws paub txog kab mob feem ntau.Ib qho kev kuaj ntshav ib leeg tau txais los ntawm colposcopy tau tshaj tawm tias qhov zoo hauv 60.6% ntawm HSIL + cov qauv.Yuav tsum tau kuaj biopsies ntxiv rau ntau qhov txhab txhawm rau txhawm rau nce rhiab heev36.Hauv qhov sib piv, UCOM, PCDHGB7, muaj qhov rhiab heev ntawm 82% rau HSIL + cov qauv, tshaj qhov rhiab heev ntawm biopsies thiab feem ntau biomarkers30.Methylation marker, FAM19A4, muaj qhov rhiab heev ntawm 69% rau CIN2+, uas zoo ib yam li cytology, tab sis tsis tuaj yeem sib txawv CIN1 los ntawm cov qauv ib txwm37.UCOMs tau pom tias yog ib qho kev tshawb nrhiav pom ntxov dua biomarker.Piv nrog rau cov kws kho mob uas muaj kev paub dhau los, UCOMs muaj kev paub zoo tshaj plaws rau cov qog nqaij hlav thaum ntxov, uas ua rau muaj kev txhim kho mob qog noj ntshav thiab muaj sia nyob 30.Tsis tas li ntawd, UCOMs muab lub vev xaib tshawb nrhiav uas nkag mus rau thaj chaw uas tsis muaj cov kws paub txog kab mob thiab txhim kho kev tshawb pom zoo.Nrog rau cov txheej txheem kuaj thiab kuaj pom tsis zoo, UCOM kev tshawb nrhiav tau txais txiaj ntsig zoo thiab txhais tau yooj yim uas zoo dua rau kev soj ntsuam raws li xav tau tsawg dua cov neeg ua haujlwm thiab cov peev txheej kho mob.
Yooj yim rau kev kuaj xyuas
Cov txheej txheem tam sim no rau kev tshawb nrhiav DNA methylation yog qhov nyuaj thiab siv sijhawm ntev.Feem ntau ntawm txoj kev xav tau kev hloov pauv bisulfite, uas ua rau poob ntawm cov qauv zoo thiab tej zaum yuav ua rau tsis ruaj khov thiab tsis raug.Kev tsim tawm tsis zoo tshwm sim los ntawm kev kho bisulfite tuaj yeem ua rau muaj kev tsis sib haum xeeb rau cov kws kho mob thiab cov neeg mob thiab cuam tshuam ntxiv rau kev soj ntsuam thiab / lossis cov tswv yim kho mob.Yog li ntawd, peb tau hloov kho txoj hauv kev ntawm UCOM nrhiav kom tsis txhob muaj teeb meem kev kho bisulfite ntawm cov qauv, ua raws li cov kev cai thov kev kho mob, thiab txhim kho kev siv tau.Peb tau tsim ib txoj hauv kev tshiab uas siv cov tshuaj methylation-rhiab heev txwv enzymes ua ke nrog lub sijhawm tiag tiag fluorescent quantitative PCR (Me-qPCR) txhawm rau txheeb xyuas cov xwm txheej methylation ntawm UCOMs hauv 3 h siv cov txheej txheem tuav tau yooj yim (Daim duab 3).Me-qPCR tuaj yeem ua tau raws li ntau hom qauv, xws li kev soj ntsuam kev sau cov kab mob hauv lub cev thiab cov qauv tso zis rau tus kheej.Cov kev kuaj mob sau tau tuaj yeem ua tiav, khaws cia, thiab yooj yim txuas mus rau kev tshawb pom siv cov txheej txheem thiab kev siv DNA rho tawm.Cov DNA rho tawm tuaj yeem raug siv ncaj qha mus rau Me-qPCR platform rau ib lub lauj kaub cov tshuaj tiv thaiv thiab cov txiaj ntsig tau txais txiaj ntsig.Tom qab kev txheeb xyuas cov txiaj ntsig tau yooj yim siv cov qauv kuaj pom zoo thiab siv tau rau qee hom mob qog noj ntshav, qhov kev txiav txim zaum kawg ntawm UCOM nrhiav pom tau raug txhais thiab nthuav tawm raws li tus nqi ib nrab.Lub Me-qPCR platform ua tau zoo dua cov tsoos bisulfite-pyrosequencing hauv UCOM tshawb pom thaum txuag 3 h ntawm bisulfite hloov dua siab tshiab, raws li EZ DNA Methylation-Gold cov khoom siv raws tu qauv.Lub tshiab methylation nrhiav tau platform ua rau UCOM nrhiav kom tau ruaj khov, muaj tseeb dua, thiab siv tau ntau dua30.
Daim duab 3 Kev txheeb xyuas cov txheej txheem ntawm UCOMs.Cov qauv muaj xws li cov qauv ua qauv BALF, Pap txhuam, thiab / lossis cov zis uas tus kheej tau sau.Cov txheej txheem DNA rho tawm tuaj yeem haum rau lub tshuab rho tawm tsis siv neeg, cov khoom lag luam tuaj yeem tshawb pom ncaj qha los ntawm qPCR.
Kev siv UCOMs
Mob ntsws cancer
Mob ntsws cancer yog qhov thib ob feem ntau kuaj mob thiab feem ntau mob qog noj ntshav thoob ntiaj teb, suav txog 11.4% ntawm cov neeg mob tshiab thiab 18.0% ntawm cov neeg tuag tshiab1.Ntawm txhua qhov kev kuaj mob, 85% yog non-me me ntsws ntsws cancer (NSCLC) thiab 15% yog mob ntsws cancer me me (SCLC), uas muaj qib siab dua ntawm malignancy38.Low-dose computed tomography (LDCT) scanning yog tam sim no pom zoo txoj kev kuaj mob ntsws cancer thiab tau pom tias yuav txhim kho kev tshawb pom ntxov thiab txo kev tuag6;Txawm li cas los xij, vim muaj qhov tshwj xeeb tsawg thiab kev siv tsis zoo, LDCT tseem tsis tau ua txoj hauv kev zoo txaus siab, ib yam li lwm cov cim kab mob qog noj ntshav, xws li CEA39.Tus nqi thiab lub peev xwm rau kev kuaj tsis tau thiab kuaj tsis raug ntawm LDCT kev tshuaj ntsuam xyuas lub tswv yim cuam tshuam qhov kev nce qib ntawm kev kuaj mob ntsws cancer nce qib 40.HIST1H4F, UCOM, muaj peev xwm loj heev raws li kev tshawb pom ntxov biomarker hauv bronchoalveolar kua (BALF) cov qauv 27.HIST1H4F yog hypermethylated nyob rau hauv lub ntsws adenocar-cinoma thiab ntsws squamous cell carcinoma, nrog rau kev kuaj pom qhov tshwj xeeb ntawm 96.7% thiab rhiab heev ntawm 87.0% (Daim duab 4A), thiab kev ua tau zoo tshwj xeeb rau theem I mob qog noj ntshav27.HIST1H4F muaj qhov tshwj xeeb ntawm 96.5% thiab rhiab heev ntawm 85.4% rau NSCLC, thiab 96.5% thiab 95.7%, feem, rau SCLC27.Tsis tas li ntawd, cov qauv ntawm yim lwm hom mob qog noj ntshav, suav nrog cov qog nqaij hlav pancreatic thiab cov qog nqaij hlav hauv plab, tau lees paub tias HIST1H4F yog hypermethylated hauv txhua yim hom27.
Cervical cancer
Kev mob khees xaws ncauj tsev menyuam yog qhov thib plaub feem ntau kuaj mob qog noj ntshav thiab thib plaub ua rau mob qog noj ntshav hauv cov poj niam hauv xyoo 2020, suav txog 3.1% ntawm cov neeg mob tshiab thiab 3.4% ntawm cov neeg mob qog noj ntshav thoob ntiaj teb1.Txhawm rau tshem tawm mob qog noj ntshav hauv tsev menyuam los ntawm 2030, raws li tau hais los ntawm WHO, kev tshawb pom ntxov ntawm qog noj ntshav yog qhov tsim nyog.Yog tias kuaj pom thaum ntxov, 5-xyoo kev ciaj sia nce mus txog 92% nrog kev mob qog noj ntshav hauv tsev menyuam 41.Lub koom haum American Cancer Society (ACS) cov lus qhia qhia txog kev kuaj mob ncauj tsev menyuam, kuaj HPV thawj zaug, lossis kev sim tshuaj ntsuam xyuas42.Cervical cytology yog invasive thiab tsuas tuaj yeem ntes 63.5% ntawm CIN2 + mob37.
PCDHGB7, qhov sib txawv, tau ua tau zoo dua siv Pap smears thiab qhov chaw mos, thiab tuaj yeem sib txawv HSIL los ntawm LSIL hauv ib qho ultra-thaum ntxov.PCDHGB7 ib leeg muaj qhov rhiab heev ntawm 100.0% thiab qhov tshwj xeeb ntawm 88.7% rau mob qog noj ntshav (Daim duab 4B), thiab 82.1% rhiab heev thiab 88.7% tshwj xeeb rau HSIL + cov qauv30.PCDHGB7 kuj tseem muaj 90.9% rhiab heev thiab 90.4% tshwj xeeb hauv cov qauv tso pa tawm ntawm qhov chaw mos rau kev mob qog noj ntshav, uas yooj yim dua los sau 30.Thaum ua ke nrog cov kev pheej hmoo siab (hr) HPV kuaj lossis Thinprep Cytology Test (TCT), PCDHGB7 muaj qhov nce siab ntawm 95.7% thiab qhov tshwj xeeb ntawm 96.2%, qhov tseem ceeb tshaj qhov kuaj hrHPV (20.3%), TCT (51.2% ), thiab ob qhov sib xyaw ua ke (57.8%) rau mob qog noj ntshav 30.PCDHGB7 kuj tau pom tias yog hypermethylated hauv 17 hom mob qog noj ntshav los ntawm TCGA cov ntaub ntawv, qhia tias nws tsim nyog hauv UCOM tsev neeg30.
Daim duab 4 UCOMs tau raug lees paub nyob rau hauv plaub hom mob qog noj ntshav hauv kev tshawb fawb loj.A. Kev ua tau zoo ntawm HIST1H4F, UCOM, hauv kev kuaj mob ntsws cancer ntawm 508 cov qauv.B. Kev ua tau zoo ntawm PCDHGB7, UCOM, hauv kev kuaj mob qog noj ntshav ntawm 844 cov qauv.C. Kev ua tau zoo ntawm PCDHGB7, UCOM, hauv kev kuaj mob qog noj ntshav endometrial ntawm 577 endometrial Pap thiab Tao txhuam cov qauv.D. Kev ua tau zoo ntawm SIX6, UCOM, hauv kev kuaj mob qog noj ntshav urothelial ntawm 177 cov qauv.
EC
EC yog ib qho ntawm cov poj niam feem ntau cov kab mob qog noj ntshav thoob ntiaj teb, nrog kwv yees li 4.2 lab tus neeg mob tshiab thiab 1% ntawm cov neeg mob qog noj ntshav tuag txhua xyoo.Nrog rau kev kuaj mob ua tiav ntawm lub sijhawm anearly, EC yog kho tau thiab muaj 5-xyoo txoj sia nyob ntawm 95% rau theem I mob qog noj ntshav.Cov neeg mob uas muaj cov tsos mob, xws li uterine los ntshav, tau txais kev soj ntsuam xyuas raws sij hawm thiab tau txais cov txheej txheem mob thiab mob, txawm tias tsuas yog 5% -10% thaum kawg tsim EC43.Transvaginal ultra- suab, raws li txoj kev tshawb pom, yog qhov tsis muaj kev ntseeg siab heev vim nws tsis muaj peev xwm sib txawv benign los ntawm malignant endo-metrial hloov pauv thiab siab tsis tseeb-zoo npaum li cas44.
Kev sib piv ntawm cov ntshav CA-125, ib qho kev siv dav hauv EC biomarker, thiab PCDHGB7 tau ua.Serum CA-125 muaj qhov rhiab heev ntawm 24.8%, uas qhia tias CA-125 yog tus cim tsis txaus rau EC txawm tias qhov tshwj xeeb ntawm 92.3% 31.PCDHGB7 kuaj pom siv Pap txhuam cov qauv ua rau muaj kev nkag siab ntawm 80.65% thiab qhov tshwj xeeb ntawm 82.81% rau ECatall theem, thaum Tao txhuam muaj qhov rhiab heev ntawm 61.29% thiab qhov tshwj xeeb ntawm 95.31% 31.PCDHGB7 kuaj qauv, raws li Me-qPCR, yielded rhiab heev ntawm 98.61%, ib tug meej ntawm 60.5%, thiab tag nrho cov raug ntawm 85.5%, siv Pap thiab Tao txhuam cov qauv (Daim duab 4C) 31.
Urothelial mob cancer
Kev mob qog noj ntshav urothelial, uas muaj lub zais zis, lub raum plab, thiab cov qog nqaij hlav hauv lub cev, yog qhov thib xya uas mob qog noj ntshav ntau tshaj plaws hauv xyoo 2020 thoob ntiaj teb, ua rau 5.2% ntawm cov neeg mob tshiab thiab 3.9% ntawm cov neeg tuag1.Cov qog nqaij hlav Urothelial, ntau dua 50% ntawm cov qog nqaij hlav zais zis, yog thib plaub feem ntau kuaj mob qog noj ntshav hauv Tebchaws Meskas hauv xyoo 2022, suav txog 11.6% ntawm cov neeg mob tshiab3.Kwv yees li ntawm 75% ntawm cov qog nqaij hlav zais zis tau muab cais ua cov qog nqaij hlav qog nqaij hlav zais zis txwv tsis pub mucosa lossis submucosa45.Ib qho cystoscopy biopsy yog tus qauv kub rau kev kuaj mob qog noj ntshav urothelial siv los ntawm fluorescence hauv situ hybridization (FISH) thiab cytology kuaj.FISH thiab cytology muaj kev kuaj mob tsis zoo, thiab cystoscopy yog qhov cuam tshuam thiab muaj qhov pheej hmoo ntawm cov kab mob uas ploj lawm, txhais cov kab mob tsis raug, thiab muaj feem ua rau kis tau lossis rov mob qog noj ntshav46.Yav dhau los validate UCOM, PCDHGB7, kuj tau pom tias yog hypermethylated nyob rau hauv urothelial cancer, nrog ib cheeb tsam nyob rau hauv lub nkhaus ntawm 0.86, qhia ib tug muaj peev xwm kuaj mob30.Txhawm rau kom siv tau ntau dua UCOMs thiab ua kom haum rau ntau hom qauv, SIX6, ib qho tshiab UCOM, tau tshuaj xyuas thiab pom muaj peev xwm kuaj tau zoo hauv kev tshawb pom ntxov ntawm urothelial cancer siv cov zis kuaj ntawm Me-qPCR platform.SIX6 kev kuaj pom siv cov zis kuaj pom tau tias muaj kev sib tw rhiab heev ntawm 86.7% thiab qhov tshwj xeeb ntawm 90.8% (Daim duab 4D), thaum tsis muaj kev cuam tshuam thiab yooj yim kom tau txais32.Lub peev xwm ntawm SIX6 nyob rau hauv kev tshuaj xyuas metastasis thiab kev ntsuas kev kho mob tam sim no tab tom tshawb xyuas.
Lub neej yav tom ntej thiab kev sib tw
UCOMs muaj kev ua tau zoo hauv kev kuaj mob muaj peev xwm ntawm ntau yam qog nqaij hlav, tab sis tseem muaj ntau txoj haujlwm ua.Peb tau nthuav dav cov npe ntawm UCOMs thiab tau nquag siv UCOMs hauv ntau hom mob qog noj ntshav, suav nrog cov kab mob uas ib txwm nyuaj los kuaj xyuas.Cov txiaj ntsig tau lees paub los ntawm TCGA cov ntaub ntawv tau tshaj tawm qhov kev thov ntawm UCOMs hauv ntau hom mob qog noj ntshav thiab ntau qhov xwm txheej.Hauv kev tshawb nrhiav ua ntej, UCOMs tau pom tias muaj peev xwm kuaj tau zoo rau cholangiocarcinomas thiab pancreatic adenocarcinomas, uas yuav luag tsis tuaj yeem kuaj pom nyob rau hauv ib nrab theem nrog kev tshuaj ntsuam tam sim no32,47.Lub peev xwm los kuaj pom cov qog nqaij hlav tsawg nrog UCOMs tuaj yeem siv nrog cov qog qog DNA (ctDNA) los ntawm kev txhim kho kua biopsy platform48.Ib txoj kev tshawb nrhiav uas muaj plasma DNA-based pan-cancer detection vaj huam sib luag ua rau muaj kev nkag siab ntawm 57.9% 49.Txawm hais tias muaj qhov tshwj xeeb siab, qhov kev ua tau zoo tag nrho qhia tau tias tseem muaj chaw rau kev txhim kho.
Cov yam ntxwv tshwj xeeb ntawm UCOMs kuj tau txhawb nqa kev tshawb fawb ntawm UCOM lub peev xwm hauv kev tshuaj xyuas kev ua tau zoo thiab kev saib xyuas rov tshwm sim.Raws li Kev Ntsuam Xyuas Kev Ntsuam Xyuas Cov Txheej Txheem hauv Cov Tumors (RECIST), kev kuaj pom kev kho mob yog cov txheej txheem pom zoo rau kev soj ntsuam rov qab thiab kev ntsuas kev kho mob, thaum cov cim qog siv ib leeg rau kev ntsuas 50.Qhov tseeb tiag, txawm li cas los xij, kev ntsuas kev ntsuas tau cuam tshuam zoo heev los ntawm qhov zaus thiab sijhawm, thiab yog li ua rau cov neeg mob muaj kev pheej hmoo siab dua thiab raug nqi 51,52.SIX6 tau raug lees paub los ua tus kws tshaj lij rau kev mob qog noj ntshav mis 32.Kev soj ntsuam ua kua biopsy-based ctDNA ua rau muaj kev soj ntsuam hauv lub sijhawm dhau los ntawm cov kab mob uas tsis tshua muaj nyob hauv lub hlis ua ntej ntawm kev kuaj pom hluav taws xob, qhov zoo tshaj plaws ncua sijhawm thiab tiv thaiv kev mob qog noj ntshav rov qab los ntawm kev mob qog noj ntshav53.Cov txiaj ntsig ua ntej qhia tias UCOMs cuam tshuam txog qib ntawm kev mob qog noj ntshav hypermethylation hauv lub sijhawm tam sim tom qab kev phais thiab kev kho mob32.Lub siab rhiab heev uas tau nthuav tawm los ntawm UCOMs thiab kev siv tau rau hauv ntau yam tsis muaj kev cuam tshuam cov qauv tso cai rau UCOMs los ua qhov tseeb rov tshwm sim mon-itoring biomarker thaum tswj cov neeg mob siab ua raws li.
Nyob rau tib lub sijhawm, pej xeem nkag mus rau qhov kev xeem yog lwm qhov teeb meem loj uas yuav tsum tau siv zog ntxiv.Thaum UCOM kev tshawb nrhiav kev sib koom tes tau txais kev pom zoo hauv tsev kho mob ntau dua hauv kev cia siab tias yuav muaj txiaj ntsig zoo rau cov neeg mob ntau dua, kev tshawb nrhiav thiab kev tshuaj ntsuam xyuas tau ua haujlwm zoo hauv Suav teb nyob deb nroog.UCOMs xav tau kev nkag mus tau zoo dua kom tsim nyog raws li cov cuab yeej tshuaj ntsuam xyuas tau, tshwj xeeb tshaj yog rau cov cheeb tsam tsis tau tsim kho.
Thaum UCOM daim ntawv thov ua rau pom thaum ntxov tau cog lus tseg, ntau yam tsis paub txog UCOM muaj nyob.Nrog rau kev tshawb nrhiav nquag, kev tshawb fawb ntxiv tau lees paub txog vim li cas UCOMs muaj nyob thoob plaws hauv cov qog nqaij hlav.Cov txheej txheem tswj hwm epigenetic hauv qab UCOMs tsim nyog rau kev tshawb nrhiav ntxiv, uas tuaj yeem ua pov thawj qhov kev taw qhia tshiab rau kev kho mob qog noj ntshav.Rov qab mus rau kev sib cuam tshuam ntawm qog homogeneity thiab heterogeneity, peb xav tias yog vim li cas UCOMs tuaj yeem yog qhov tshwj xeeb rau feem ntau ntawm cov qog nqaij hlav qog noj ntshav uas txuas nrog rau qee yam mob qog noj ntshav.Lub luag haujlwm ntawm UCOM- txheeb xyuas DNA methylation aberrations nyob rau hauv cov qog nqaij hlav, qog kev loj hlob, thiab metastasis tsis tau txiav txim siab nyob rau hauv tus txheej txheem ntawm kev poob thiab rov ua lub cev ntawm tes thiab yuav tsum tau kuaj xyuas kom meej.Lwm qhov kev txaus siab tseem ceeb nyob hauv thaj tsam ntawm kev sib koom ua ke ntawm kev sib koom ua ke ntawm UCOMs nrog cov ntaub so ntswg-cov cim cim nyob rau hauv kev cia siab ntawm kev ua kom pom tseeb ntawm cov kab mob qog noj ntshav thiab kev txheeb xyuas cov qog nqaij hlav hauv qhov rov qab.UCOMs tuaj yeem tau txais cov cuab yeej zoo tshaj plaws los tiv thaiv qog noj ntshav, kuaj mob qog noj ntshav, thiab muaj peev xwm tiv thaiv thiab tshem tawm qog noj ntshav.
Muab kev txhawb nqa
Txoj haujlwm no tau txais kev txhawb nqa los ntawm National Key R&D Program ntawm Tuam Tshoj (Grant No. 2022BEG01003), National Natural Science Foundation of China (Grant Nos. 32270645 thiab 32000505), ib qho nyiaj pab los ntawm Heilongjiang Provincial Health Commission (Grant No. 2020-111) , thiab ib qho nyiaj pab los ntawm Heze Science thiab Technology Institute (Grant No. 2021KJPT07).
Kev tsis sib haum xeeb ntawm kev txaus siab nqe lus
Wei Li yog R&D Tus Thawj Coj rau Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu ua haujlwm rau Pawg Thawj Saib Xyuas Kev Tshawb Fawb ntawm Epiprobe.W. Yu thiab Epiprobe tau pom zoo tseem tos patents ntsig txog txoj haujlwm no.Tag nrho lwm tus kws sau ntawv tshaj tawm tsis muaj kev sib tw nyiam.
Sau cov nyiaj pab
Tsim thiab tsim qhov project: Chengchen Qian thiab Wenqiang Yu.
Sau daim ntawv: Chengchen Qian.
Ua cov illustrations: Chengchen Qian.
Tshuaj xyuas thiab kho cov ntawv sau: Xiaolong Zou, Wei Li, Yinshan Li thiab Wenqiang Yu.
Cov ntaub ntawv
1. Sung H, Ferlay J, Siegel RL, LaversanneM, Soerjomataram I, Jemal A, et al.Ntiaj teb Cancer Statistics 2020: GLOBOCAN kwv yees ntawm
Kev tshwm sim thiab kev tuag thoob ntiaj teb rau 36 mob qog noj ntshav hauv 185 lub teb chaws.CA Cancer J Clin.2021;71:209–49.
2. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al.Cov txheeb cais mob qog noj ntshav hauv Suav teb thiab Tebchaws Meskas, 2022: cov ntaub ntawv, cov qauv, thiab kev txiav txim siab.Chin MedJ (English).2022;135: 584-90.
3. Siegel RL, Miller KD, WagleNS, JemalA.Cancer statistics, 2023. CA Cancer J Clin.2023;73:17–48.
4. Crosby D, BhatiaS, Brindle KM, Coussens LM, Dive C, Emberton M, et al.Kev tshawb pom ntxov ntawm mob qog noj ntshav.Kev tshawb fawb.2022;375 :ua 9040.
5. Ladabaum U, Dominitz JA, KahiC, Schoen RE.Tswv yim rau
kuaj mob qog nqaij hlav hauv plab.Gastroenterology.2020;158:418-32.
6. Tanoue LT, Tanner NT, Gould MK, Silvetri GA.Kev kuaj mob ntsws cancer.Am J Respir Crit Care Med.2015;191:19–33.
7. Bouvard V, WentzensenN, Mackie A, Berkhof J, BrothertonJ, Giorgi-Rossi P, et al.IARC qhov kev xav ntawm kev kuaj mob qog noj ntshav hauv tsev menyuam.N EnglJ Med.2021;385: 1908-18.
8. Xue P, Ng MTA, QiaoY.Cov teeb meem ntawm colposcopy rau kev kuaj mob qog noj ntshav hauv tsev menyuam hauv LMICs thiab kev daws teeb meem los ntawm kev txawj ntse.BMC Med.2020;18:169 : kuv.
9. Johnson P, Zhou Q, Dao DY, Lo YMD.Circulating biomarkers nyob rau hauv kev kuaj mob thiab kev tswj ntawm hepatocellular carcinoma.Nat Rev Gastroenterol Hepatol.2022;19:670-81.
10. Van PoppelH, Albreht T, Basu P, HogenhoutR, CollenS, Roobol M. Serum PSA-raws li kev tshawb pom ntxov ntawm prostate cancer hauv Europe thiab thoob ntiaj teb: yav dhau los, tam sim no thiab yav tom ntej.Nat Rev Urol.2022;19:
562-72 : kuv.
11. HolyoakeA, O'Sullivan P, Pollock R, Best T, Watanabe J, KajitaY,
ua al.Kev txhim kho ntawm multiplex RNA cov zis kuaj rau kev kuaj pom thiab stratification ntawm transitional cell carcinoma ntawm lub zais zis.Clin Cancer Res.2008;14:742-9.
12. Feinberg AP, Vogelstein B. Hypomethylation distinguishes cov noob ntawm ib co tib neeg mob qog noj ntshav los ntawm lawv ib txwm counterparts.Xwm.Xyoo 1983;301: 89-92.
13. Ng JM, Yu J. Promoter hypermethylation ntawm qog suppressor noob raws li biomarkers muaj peev xwm nyob rau hauv mob qog noj ntshav.IntJ Mol Sci.2015;16: 2472-96.
14. Esteller M. Cancer epigenomics: DNA methylomes thiab histone- hloov kho daim ntawv qhia.Nat Rev Genet.2007;8:286-98.
15. Nishiyama A, Nakanishi M. Qhia txog DNA methylation toj roob hauv pes ntawm mob qog noj ntshav.Trends Genet.2021;37:1012-27 .
16. Xie W, Schultz MD, ListerR, Hou Z, Rajagopal N, Ray P, et al.Epigenomic tsom xam ntawm multilineage sib txawv ntawm tib neeg embryonic qia hlwb.Cell.2013;153: 1134-48.
17. Li Y., Zheng H, Wang Q, Zhou C, WeiL, Liu X, et al.Genome-wide analyses qhia lub luag haujlwm ntawm Polycomb hauv kev txhawb nqa hypomethylation ntawm DNA methylation hav.Genome Bio.2018;19:18.
18. Koch A, JoostenSC, Feng Z, de Ruijter TC, DrahtMX, MelotteV,
ua al.Kev tshuaj xyuas DNA methylation hauv qog noj ntshav: qhov chaw rov mus xyuas.Nat Rev Clin Oncol.2018;15:459-66.
19. KleinEA, Richards D, Cohn A, TummalaM, Lapham R, Cosgrove D, et al.Clinical validation ntawm lub hom phiaj methylation-raws li multi-cancer thaum ntxov kuaj kuaj siv ib tug ywj siab validation teeb.Ann Oncol.2021;32: 1167-77.
20. Hanahan D, Weinberg RA.Cov cim ntawm mob qog noj ntshav.Cell.2000;100:57-70.
21. Hanahan D. Hallmarks of cancer: tshiab dimension.Cancer Discov.2022;12:31-46.
22. Schwartzberg L, Kim ES, Liu D, Schrag D. Precision oncology: leej twg, ua li cas, dab tsi, thaum twg, thiab thaum twg tsis?Am Soc Clin Oncol Educ Phau Ntawv.2017: 160-9.
23. Liu H, Meng X, Wang J. Realtime quantitative methylation
Kev kuaj pom ntawm PAX1 noob hauv kev kuaj mob qog noj ntshav.IntJ Gynecol Cancer.2020;30: 1488-92.
24. Imperiale TF, RansohoffDF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al.Multitargetstool DNA kuaj rau kev kuaj mob qog nqaij hlav hauv plab.N EnglJ Med.2014;370: 1287-97.
25. Li J, Li Y, Li W, Luo H, Xi Y, Dong S, et al.Qhia qhov chaw
Sequences txheeb xyuas cov qauv DNA methylation tsis zoo uas hloov pauv tus kheej ntawm tes thiab cov qog-tiv thaiv kab mob sib txuas.Genome
Res.2019;29:270-80.
26. Gao Q, LinYP, Li BS, Wang GQ, Dong LQ, Shen BY, et al.Unintrusive multi-cancer detection los ntawm circulating cell-free DNA methylation sequencing (THUNDER): kev loj hlob thiab kev tshawb fawb ywj siab.Ann Oncol.2023;34:486-95.
27. Dong S, Li W, Wang L, Hu J, Song Y, Zhang B, et al.Histone-related genes yog hypermethylated hauv ntsws cancer thiab hypermethylated
HIST1H4F tuaj yeem ua haujlwm rau pan-cancer biomarker.Cancer Res.2019;79:6101-12.
28. HeijnsdijkEA, Wever EM, AuvinenA, Hugosson J, Ciatto S, Nelen V, et al.Kev ua tau zoo-ntawm-lub neej cuam tshuam ntawm kev tshuaj ntsuam prostate-specific antigen.N EnglJ Med.2012;367: 595-605.
29. LuzakA, Schnell-Inderst P, Bühn S, Mayer-Zitarosa A, Siebert U. Clinical efficiency of cancer biomarker tests are offered as self-pay health services: a systematic review.Eur J Public Health.2016;26: 498-505 .
30. Dong S, Lu Q, Xu P, Chen L, Duan X, Mao Z, et al.
Hypermethylated PCDHGB7 raws li kev mob qog noj ntshav thoob ntiaj teb tsuas yog cim thiab nws daim ntawv thov hauv kev kuaj mob qog noj ntshav thaum ntxov.Clin Transl Med.2021;11: e457.
31. Yuan J, Mao Z, Lu Q, Xu P, Wang C, Xu X, et al.Hypermethylated PCDHGB7 ua biomarker rau kev tshawb pom ntxov ntawm endometrial cancer hauv endometrial txhuam cov qauv thiab lub ncauj tsev menyuam scrapings.Pem Hauv Ntej Mol Biosci.2022;8 :774215.
32. Dong S, Yang Z, Xu P, Zheng W, Zhang B, Fu F, et al.Kev sib nrig sib
tshwj xeeb epigenetic hloov kho ntawm SIX6 nrog hypermethylation rau precancerous theem thiab metastasis tshwm sim tracing.Teeb liab Transduct Target Ther.2022;7:208 ib.
33. Huang L, Guo Z, Wang F, Fu L. KRAS kev hloov pauv: los ntawm undruggable mus druggable nyob rau hauv mob cancer.Teeb liab Transduct Target Ther.2021;6:386 ib.
34. Belinsky SA, Nikula KJ, PalmisanoWA, MichelsR, SaccomannoG, GabrielsonE, et al.Aberrant methylation ntawm p16 (INK4a) yog qhov tshwm sim nyob rau hauv lub ntsws cancer thiab muaj peev xwm biomarker rau kev kuaj mob ntxov.Proc Natl Acad Sci U.S.A.Xyoo 1998;95:11891-6.
35. Robertson KD.DNA methylation thiab tib neeg kab mob.Nat Rev Genet.2005;6: 597-610.
36. WentzensenN, Walker JL, Kub MA, Smith KM, ZunaRE,
Mathews C, et al.Ntau qhov kev kuaj pom thiab kuaj pom cov qog nqaij hlav qog noj ntshav ua ntej ntawm colposcopy.J Clin Oncol.2015;33:83-9.
37. De Strooper LM, Meijer CJ, Berkhof J, Hesselink AT, Snijders
PJ, Steenbergen RD, et al.Kev tsom xam Methylation ntawm FAM19A4
gene nyob rau hauv lub ncauj tsev menyuam scrapes yog heev npaum nyob rau hauv kev kuaj xyuas lub ncauj tsev menyuam
carcinomas thiab qib siab CIN2/3 lesions.Cancer Prev Res (Phila).2014;7:1251-7.
38. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS.Mob ntsws cancer.Lancet.2021;398: 535-54.
39. Grunnet M, Sorensen JB.Carcinoembryonic antigen (CEA) ua cov qog nqaij hlav hauv ntsws cancer.Mob ntsws cancer.2012;76:138-43.
40. Wood DE, KazerooniEA, Baum SL, EapenGA, EttingerDS, Hou L, et al.Kev kuaj mob ntsws cancer, Version 3.2018, NCCN Clinical Practice Guidelines in Oncology.J Natl Compr Canc Netw.2018;16:412-41.
41. American Cancer Society.Cancer facts & figures.Atlanta, GA, USA: American Cancer Society;2023 [hloov kho 2023 Lub Peb Hlis 1;hais txog 2023 Lub Yim Hli 22].
42. FonthamETH, Hma AMD, Church TR, EtzioniR, Paj CR,
Herzig A, et al.Kev kuaj mob khees xaws ncauj tsev menyuam rau cov tib neeg muaj qhov pheej hmoo nruab nrab: 2020 cov lus qhia hloov tshiab los ntawm American Cancer Society.CA Cancer J Clin.2020;70:321-46.
43. Clarke MA, Long BJ, Del Mar MorilloA, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Koom haum ntawm kev pheej hmoo mob qog noj ntshav endometrial nrog los ntshav tom qab yug menyuam hauv cov poj niam: kev tshuaj xyuas thiab kev tshuaj xyuas.JAMA Intern Med.2018;178:1210–22 .
44. Jacobs I, Gentry-MaharajA, Burnell M, ManchandaR, Singh N,
Sharma A, et al.rhiab heev ntawm transvaginal ultrasound kuaj
rau kev mob qog noj ntshav endometrial hauv cov poj niam postmenopausal: kev tshawb fawb txog kev tswj xyuas hauv UKCTOCS pawg.Lancet Oncol.2011;12:38-48.
45. BabjukM, Burger M, CompératEM, Gontero P, MostafidAH,
PaloJ, et al.European Association of Urology Guidelines on Non- muscle-invasive Bladder Cancer (TaT1 thiab Carcinoma In Situ) -
2019 Update.Ua Url.2019;76: 639-57.
46. Aragon-Ching JB.Kev sib tw thiab kev nce qib hauv kev kuaj mob, biology, thiab kev kho mob ntawm urothelial sab sauv thiab zais zis carcinomas.Urol Oncol.2017;35:462-4.
47. Rizvi S, KhanSA, Hallemeier CL, Kelley RK, Gores GJ.
Cholangiocarcinoma - cov tswv yim hloov zuj zus thiab cov tswv yim kho mob.Nat Rev Clin Oncol.2018;15:95-111.
48. Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy nyob rau hauv hepatocellular
carcinoma: circulating qog cell thiab circulating qog DNA.Mol Cancer.2019;18:114 : kuv.
49. Zhang Y, Yao Y, Xu Y, Li L, Gong Y, Zhang K, et al.Pan-mob cancer
circulating qog DNA nrhiav tau nyob rau hauv ntau tshaj 10,000 tus neeg mob Suav.Nat Commun.2021;12:11 .
50. Eisenhauer EA, Therasse P, BogaertsJ, Schwartz LH, Sargent D, Ford R, et al.Cov txheej txheem kev ntsuas cov lus teb tshiab hauv cov qog nqaij hlav: kho RECIST cov lus qhia (version 1.1).Eur J Cancer.2009;45:228-47.
51. LitièreS, Collette S, de Vries EG, Seymour L, BogaertsJ.RECIST - kawm yav dhau los los tsim lub neej yav tom ntej.Nat Rev Clin Oncol.
2017;14:187-92.
52. Seymour L, BogaertsJ, Perrone A, FordR, Schwartz LH, Mandrekar S, et al.iRECIST: cov lus qhia rau cov lus teb rau kev siv hauv kev sim
kuaj immunotherapeutics.Lancet Oncol.2017;18: e143-52.
53. PantelK, Alix-Panabières C. Ua kua biopsy thiab cov kab mob tsawg tsawg - qhov kev nce qib tshiab thiab cuam tshuam rau kev kho.Nat Rev Clin Oncol.2019;16:409-24.
Cite this article as: Qian C, Zou X, Li W, Li Y, Yu W. The outpost against cancer: universal cancer only markers.Cancer Biol Med.2023;20: 806-815.
doi: 10.20892/j.issn.2095-3941.2023.0313 ib.
Post lub sij hawm: May-07-2024