Txoj kev tshawb nrhiav yav tom ntej: PCR-based ntshav ctDNA methylation thev naus laus zis qhib lub sijhawm tshiab ntawm MRD soj ntsuam rau mob qog noj ntshav

Tsis ntev los no, JAMA Oncology (IF 33.012) luam tawm ib qho kev tshawb fawb tseem ceeb [1] los ntawm pab neeg ntawm Prof. Cai Guo-ring los ntawm Tsev Kho Mob Cancer ntawm Fudan University thiab Prof. Wang Jing los ntawm Renji Tsev Kho Mob ntawm Shanghai Jiao Tong University Tsev Kawm Ntawv ntawm Tshuaj, hauv Kev sib koom tes nrog KUNYUAN BIOLOGY: "Kev Tshawb Nrhiav Thaum Ntxov ntawm Molecular Residual Disease thiab Risk Stratification rau Theem I txog III Kab Mob Ntshav Qab Zib los ntawm Circulating qog DNA Methylation thiab Risk Stratification). Txoj kev tshawb no yog thawj qhov kev tshawb fawb ntau hauv ntiaj teb los siv PCR-raws li ntshav ctDNA multigene methylation thev naus laus zis rau kev kho mob qog noj ntshav hauv plab thiab rov qab saib xyuas dua, muab cov txheej txheem kev siv nyiaj ntau dua thiab kev daws teeb meem piv nrog MRD nrhiav cov thev naus laus zis uas twb muaj lawm, uas xav tau. txhawm rau txhim kho kev kho mob zoo heev ntawm kev siv tshuaj kho mob qog noj ntshav hauv plab hnyuv rov tshwm sim thiab saib xyuas, thiab txhim kho cov neeg mob muaj sia nyob thiab lub neej zoo. Txoj kev tshawb no kuj tau soj ntsuam zoo heev los ntawm phau ntawv xov xwm thiab nws cov neeg kho, thiab tau teev npe raws li cov ntawv pom zoo tseem ceeb hauv qhov teeb meem no, thiab xibfwb Juan Ruiz-Bañobre los ntawm Spain thiab xibfwb Ajay Goel los ntawm Tebchaws Meskas tau raug caw tuaj xyuas. Txoj kev tshawb no kuj tau tshaj tawm los ntawm GenomeWeb, uas yog thawj coj ntawm biomedical media hauv Tebchaws Meskas.

Mob qog nqaij hlav hauv plab (CRC) yog ib qho mob qog nqaij hlav hauv plab hnyuv hauv Suav teb. 2020 International Agency for Research on Cancer (IARC) cov ntaub ntawv qhia tias 555,000 tus neeg mob tshiab hauv Suav teb suav txog li 1/3 ntawm lub ntiaj teb, nrog rau qhov xwm txheej dhia mus rau qhov chaw thib ob ntawm cov qog nqaij hlav hauv Suav teb; 286,000 tus neeg tuag suav txog kwv yees li 1/3 ntawm lub ntiaj teb, suav tias yog thib tsib feem ntau ua rau mob qog noj ntshav hauv Suav teb. Qhov thib tsib ua rau tuag hauv Suav teb. Nws yog qhov tsim nyog hais tias ntawm cov neeg mob kuaj mob, TNM theem I, II, III thiab IV yog 18.6%, 42.5%, 30.7% thiab 8.2% feem. Ntau tshaj 80% ntawm cov neeg mob yog nyob rau hauv nruab nrab thiab lig theem, thiab 44% ntawm lawv muaj ib txhij los yog heterochronic nyob deb metastases rau daim siab thiab ntsws, uas cuam tshuam rau lub sij hawm ciaj sia taus, ua phem rau kev noj qab haus huv ntawm peb cov neeg nyob thiab ua rau hnyav kev sib raug zoo thiab nyiaj txiag. lub nra. Raws li kev txheeb cais ntawm National Cancer Center, qhov nruab nrab txhua xyoo nce tus nqi ntawm kev kho mob qog noj ntshav hauv Suav teb yog li 6.9% mus rau 9.2%, thiab kev siv nyiaj noj qab haus huv ntawm cov neeg mob hauv ib xyoos ntawm kev kuaj mob tuaj yeem siv li 60% ntawm cov neeg mob. tsev neeg cov nyiaj tau los. Cov neeg mob qog noj ntshav tau raug mob los ntawm tus kab mob thiab tseem muaj kev kub ntxhov nyiaj txiag [2].
cuaj caum feem pua ​​​​ntawm cov kab mob qog nqaij hlav hauv plab tuaj yeem raug tshem tawm, thiab qhov tshwm sim ntawm cov qog ua ntej, qhov siab dua li tsib xyoos tom qab kev phais mob phais, tab sis tag nrho cov rov tshwm sim tom qab radical resection tseem yog 30%. Cov neeg muaj sia nyob tsib xyoos ntawm kev mob qog noj ntshav hauv cov neeg Suav yog 90.1%, 72.6%, 53.8% thiab 10.4% rau theem I, II, III thiab IV, feem.
Cov kab mob tsawg kawg nkaus (MRD) yog qhov ua rau mob qog noj ntshav tom qab kho radical. Nyob rau xyoo tas los no, MRD kev tshawb nrhiav thev naus laus zis rau cov qog nqaij hlav tau nce siab sai, thiab ntau qhov kev soj ntsuam hnyav thiab kev cuam tshuam tau lees paub tias tom qab kev phais MRD tuaj yeem qhia tau tias muaj kev pheej hmoo ntawm kev mob qog noj ntshav tom qab mob qog noj ntshav. Kev ntsuam xyuas ctDNA muaj qhov zoo ntawm kev ua tsis zoo, yooj yim, nrawm, nrog cov qauv siv tau zoo thiab kov yeej cov qog heterogeneity.
US NCCN cov lus qhia rau kev mob qog noj ntshav thiab Suav CSCO cov lus qhia rau kev mob qog noj ntshav ob leeg hais tias rau kev txiav txim siab txog kev pheej hmoo rov qab los thiab kev xaiv tshuaj kho mob hauv plab, ctDNA kuaj tuaj yeem muab cov ntaub ntawv pov thawj thiab kev kwv yees los pab kev txiav txim siab kho mob rau cov neeg mob theem II. los yog III mob qog noj ntshav. Txawm li cas los xij, feem ntau cov kev tshawb fawb uas twb muaj lawm tsom rau ctDNA kev hloov pauv raws li kev siv tshuab thev naus laus zis (NGS), uas muaj cov txheej txheem nyuaj, lub sijhawm ua haujlwm ntev, thiab tus nqi siab [3], nrog rau me ntsis tsis muaj kev dav dav thiab qis dua ntawm cov neeg mob qog noj ntshav.
Nyob rau hauv rooj plaub ntawm theem III cov neeg mob qog nqaij hlav hauv plab, NGS-based ctDNA dynamic saib xyuas tus nqi txog li $10,000 rau ib zaug thiab yuav tsum tau tos ntev txog li ob lub lis piam. Nrog rau kev sim multigene methylation hauv txoj kev tshawb no, ColonAiQ®, cov neeg mob tuaj yeem muaj kev soj ntsuam ctDNA dynamic ntawm ib feem kaum ntawm tus nqi thiab tau txais daim ntawv tshaj tawm hauv tsawg li ob hnub.
Raws li 560,000 tus neeg mob tshiab ntawm mob qog noj ntshav hauv Suav teb txhua xyoo, cov neeg mob kho mob feem ntau nrog theem II-III mob qog noj ntshav (qhov kev faib ua feem yog kwv yees li 70%) muaj qhov xav tau ntau dua rau kev saib xyuas dynamic, tom qab ntawd qhov kev lag luam loj ntawm MRD dynamic saib xyuas ntawm mob qog nqaij hlav hauv plab mus txog ntau lab tus tib neeg txhua xyoo.
Nws tuaj yeem pom tau tias cov txiaj ntsig kev tshawb fawb muaj qhov tseem ceeb scientific thiab cov tswv yim tseem ceeb. Los ntawm cov kev tshawb fawb soj ntsuam loj, nws tau lees paub tias PCR-raws li ntshav ctDNA multigene methylation thev naus laus zis tuaj yeem siv rau kev kwv yees mob qog noj ntshav hauv plab thiab rov qab saib xyuas nrog ob qho tib si rhiab heev, ncua sij hawm thiab nqi-zoo, zoo dua ua kom cov tshuaj muaj txiaj ntsig zoo rau cov neeg mob qog noj ntshav ntau dua. . Txoj kev tshawb no yog ua raws li ColonAiQ®, ntau lub noob methylation kuaj rau mob qog nqaij hlav hauv plab uas tsim los ntawm KUNY, uas nws cov nqi kho mob hauv kev tshuaj xyuas ntxov thiab kev kuaj mob tau lees paub los ntawm kev tshawb fawb hauv nruab nrab.
Gastroenterology (IF33.88), cov ntawv xov xwm thoob ntiaj teb saum toj kawg nkaus hauv kev kho mob plab hauv 2021, tau tshaj tawm cov txiaj ntsig kev tshawb fawb ntau ntawm Zhongshan Tsev Kho Mob ntawm Fudan University, Tsev Kho Mob Cancer ntawm Fudan University thiab lwm lub tsev kho mob muaj cai koom nrog KUNYAN Biological, uas tau lees paub. Qhov kev ua tau zoo ntawm ColonAiQ® ChangAiQ® hauv kev tshuaj xyuas ntxov thiab kev kuaj mob ntxov ntawm mob qog noj ntshav, thiab pib tshawb nrhiav Nws kuj tshawb txog qhov muaj peev xwm siv tau hauv kev soj ntsuam kev mob qog nqaij hlav hauv plab.

Txhawm rau txhawm rau txheeb xyuas daim ntawv thov kev kho mob ntawm ctDNA methylation hauv kev pheej hmoo stratification, taw qhia kev txiav txim siab kho mob thiab kev saib xyuas rov tshwm sim thaum ntxov nyob rau theem I-III mob qog noj ntshav, pab pawg tshawb fawb suav nrog 299 tus neeg mob uas muaj theem I-III mob qog noj ntshav uas tau phais radical thiab sau cov ntshav kuaj ntawm Txhua qhov kev soj ntsuam tom qab (peb lub hlis sib nrug) hauv ib lub lis piam ua ntej kev phais, ib hlis tom qab kev phais, thiab hauv kev kho mob tom qab phais rau dynamic ntshav ctDNA kuaj.
Ua ntej, nws tau pom tias kev kuaj ctDNA tuaj yeem kwv yees qhov kev pheej hmoo ntawm kev rov tshwm sim hauv cov neeg mob qog noj ntshav hauv plab thaum ntxov, ob qho tib si ua ntej thiab thaum ntxov tom qab phais. Preoperative ctDNA-positive cov neeg mob muaj qhov tshwm sim ntau dua ntawm kev rov ua haujlwm tom qab rov ua haujlwm dua li cov neeg mob ua ntej ctDNA-tsis zoo (22.0% > 4.7%). Kev kuaj ctDNA thaum ntxov tseem kwv yees qhov kev pheej hmoo rov tshwm sim: ib hlis tom qab kev txiav tawm radical, cov neeg mob ctDNA zoo yog 17.5 npaug ntau dua li cov neeg mob tsis zoo; pab neeg no kuj pom tau hais tias kev sib xyaw ctDNA thiab CEA kev ntsuas me ntsis txhim kho kev ua tau zoo hauv kev kuaj xyuas rov qab (AUC = 0.849), tab sis qhov sib txawv tsis tseem ceeb piv nrog ctDNA (AUC = 0.839) kuaj ib leeg Qhov txawv tsis tseem ceeb piv rau ctDNA ib leeg (AUC = 0.839 ib.).
Clinical staging ua ke nrog cov kev pheej hmoo yog tam sim no lub hauv paus tseem ceeb rau kev pheej hmoo stratification ntawm cov neeg mob qog noj ntshav, thiab nyob rau hauv lub tam sim no paradigm, ib tug loj tus naj npawb ntawm cov neeg mob tseem rov tshwm sim [4], thiab yuav tsum tau ceev rau cov cuab yeej stratification zoo dua li kev kho mob thiab nyob rau hauv kev kho mob coexist nyob rau hauv lub tsev kho mob. Raws li qhov no, pab pawg tau faib cov neeg mob nrog theem III mob qog noj ntshav rau hauv pawg sib txawv raws li kev soj ntsuam kev pheej hmoo rov tshwm sim (T4 / N2) thiab tsis tshua muaj kev pheej hmoo (T1-3N1)) thiab lub sijhawm kho mob ntxiv (3/6 lub hlis). Kev tshuaj xyuas pom tau hais tias cov neeg mob nyob rau hauv pawg neeg muaj kev pheej hmoo siab ntawm ctDNA-zoo cov neeg mob muaj qhov rov qab qis dua yog tias lawv tau txais rau lub hlis ntawm kev kho mob ntxiv; nyob rau hauv pawg uas tsis tshua muaj kev pheej hmoo ntawm cov neeg mob ctDNA-zoo, tsis muaj qhov sib txawv tseem ceeb ntawm lub voj voog kho mob thiab cov txiaj ntsig ntawm tus neeg mob; thaum cov neeg mob ctDNA-tsis zoo muaj qhov pom tau zoo dua li cov neeg mob ctDNA zoo thiab lub sijhawm ntev dua tom qab rov ua haujlwm tsis pub dhau (RFS); theem I thiab theem qis II mob qog noj ntshav tag nrho cov neeg mob ctDNA-negative tsis rov muaj dua li ntawm ob xyoos; Yog li ntawd, kev koom ua ke ntawm ctDNA nrog cov yam ntxwv kho mob yuav tsum tau ua kom zoo dua qhov kev pheej hmoo stratification thiab kev kwv yees zoo dua.

Daim duab 1. Kev soj ntsuam Plasma ctDNA ntawm POM1 rau kev tshawb pom ntxov ntawm kev mob qog nqaij hlav hauv plab
Cov txiaj ntsig ntxiv ntawm kev kuaj ctDNA dynamic tau pom tias qhov kev pheej hmoo ntawm kev rov ua dua tau nce siab dua hauv cov neeg mob uas muaj qhov zoo ntawm ctDNA kuaj ntau dua li cov neeg mob uas tsis zoo ctDNA thaum lub sij hawm tus kab mob rov qab saib xyuas theem tom qab kev kho mob (tom qab phais radical + adjuvant therapy) (Daim duab 3ACD), thiab tias ctDNA tuaj yeem qhia cov qog rov qab mus txog 20 lub hlis ua ntej tshaj qhov kev yees duab (Daim duab 3B), muab qhov muaj peev xwm ntawm kev tshawb pom ntxov ntawm cov kab mob rov qab thiab kev cuam tshuam raws sijhawm.

Daim duab 2. ctDNA tsom xam raws li longitudinal cohort txhawm rau kuaj mob qog nqaij hlav hauv plab

"Ntau cov kev tshawb fawb tshuaj txhais lus hauv kev mob qog nqaij hlav hauv plab ua rau kev qhuab qhia, tshwj xeeb tshaj yog ctDNA-raws li MRD kuaj pom muaj peev xwm los txhim kho kev tswj xyuas tom qab kev kho mob ntawm cov neeg mob qog nqaij hlav hauv plab los ntawm kev ua kom muaj kev pheej hmoo rov tshwm sim, coj kev txiav txim siab kho mob thiab saib xyuas kev rov tshwm sim thaum ntxov.

Qhov kom zoo dua ntawm kev xaiv DNA methylation raws li ib qho tshiab MRD marker tshaj kev hloov pauv yog tias nws tsis tas yuav tsum muaj tag nrho cov genome sequencing soj ntsuam ntawm cov qog nqaij hlav, yog siv ncaj qha rau kev kuaj ntshav, thiab zam tsis tau qhov tsis tseeb-zoo tshwm sim vim kev tshawb pom ntawm somatic mutations los ntawm ib txwm muaj. cov ntaub so ntswg, benign kab mob, thiab clonal hematopoiesis.
Txoj kev tshawb no thiab lwm yam kev tshawb fawb tau lees paub tias kev kuaj ctDNA-raws li MRD yog qhov tseem ceeb tshaj plaws ntawm kev pheej hmoo rau kev rov tshwm sim ntawm theem I-III mob qog noj ntshav thiab tuaj yeem siv los pab qhia kev txiav txim siab kho mob, suav nrog "kev nce ntxiv" thiab "kev txo qis" ntawm kev kho mob ntxiv. MRD yog qhov tseem ceeb tshaj plaws ntawm kev pheej hmoo rau kev rov tshwm sim tom qab phais rau theem I-III mob qog noj ntshav.
Lub teb ntawm MRD yog hloov zuj zus mus sai heev nrog rau ntau lub tswv yim tshiab, muaj txiaj ntsig zoo thiab cov kev ntsuam xyuas tshwj xeeb raws li epigenetics (DNA methylation thiab fragmentomics) thiab genomics (ultra-deep targeted sequencing lossis tag nrho genome sequencing). Peb cia siab tias ColonAiQ® txuas ntxiv txhim kho cov kev tshawb fawb soj ntsuam loj thiab tuaj yeem dhau los ua qhov ntsuas tshiab ntawm MRD kev sim uas suav nrog kev siv tau yooj yim, kev ua haujlwm siab thiab pheej yig thiab tuaj yeem siv dav hauv kev kho mob niaj hnub. "
Cov ntaub ntawv
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