Ubushakashatsi buteganijwe: Ikoranabuhanga rya PCR rishingiye ku maraso ctDNA methylation rifungura ibihe bishya byo kugenzura MRD kuri kanseri yibara.

Vuba aha, Oncology ya JAMA (NIBA 33.012) yasohoye ibisubizo byingenzi byubushakashatsi [1] nitsinda rya Prof. Cai Guo-ring wo mu bitaro bya kanseri byo muri kaminuza ya Fudan na Prof. Wang Jing wo mu bitaro bya Renji byo mu ishuri ry’ubuvuzi rya kaminuza ya Shanghai Jiao Tong, ku bufatanye na BIUNOGIQUE ya KUNYUAN: “Kumenya hakiri kare indwara ya kanseri y’indwara ya kanseri. Tumor ADN Methylation na Risk Stratification) ”. Ubu bushakashatsi nubushakashatsi bwa mbere bwibanze ku isi bwifashishije ikoranabuhanga rya PCR rishingiye ku maraso ctDNA multigene methylation ya tekinoroji yo guhanura kanseri yo mu mara no guhanura inshuro nyinshi, itanga inzira ihendutse ya tekiniki hamwe n’igisubizo ugereranije n’uburyo buriho bwa tekinoroji ya MRD yo gutahura, bikaba biteganijwe ko bizamura cyane imikoreshereze y’amavuriro yo guhanura no guhanura ubuzima bw’abarwayi. Ubushakashatsi kandi bwasuzumwe cyane n'iki kinyamakuru n'abanditsi bacyo, kandi bwashyizwe ku rutonde nk'impapuro z'ingenzi zisabwa muri iki kibazo, maze Porofeseri Juan Ruiz-Bañobre ukomoka muri Esipanye na Porofeseri Ajay Goel wo muri Amerika batumirwa kubisuzuma. Ubushakashatsi kandi bwatanzwe na GenomeWeb, itangazamakuru rikomeye ry’ibinyabuzima muri Amerika.

Kanseri yibara (CRC) ni ikibyimba gikunze kwibasira inzira ya gastrointestinal mu Bushinwa. Ikigo mpuzamahanga gishinzwe ubushakashatsi kuri kanseri (IARC) 2020 cyerekana ko abantu 555.000 bashya mu Bushinwa bangana na 1/3 cy'isi, aho umubare w'abanduye usimbukira ku mwanya wa kabiri wa kanseri zisanzwe mu Bushinwa; 286.000 bapfuye bangana na 1/3 ku isi, biza ku mwanya wa gatanu mu bitera impfu za kanseri mu Bushinwa. Impamvu ya gatanu y'urupfu mu Bushinwa. Birashimishije ko mu barwayi basuzumwe, icyiciro cya TNM I, II, III na IV ni 18,6%, 42.5%, 30.7% na 8.2%. Abarwayi barenga 80% bari mu cyiciro cyo hagati na nyuma, kandi 44% muri bo bafite metastase ya kure cyangwa itandukanye ya heterochronic kugeza ku mwijima no mu bihaha, bigira ingaruka zikomeye ku gihe cyo kubaho, bikangiza ubuzima bw'abaturage bacu kandi bigatera umutwaro uremereye mu mibereho n'ubukungu. Nk’uko imibare y’ikigo cy’igihugu gishinzwe kanseri ibigaragaza, impuzandengo y’umwaka yiyongera ku kiguzi cyo kuvura kanseri y’urura runini mu Bushinwa igera kuri 6.9% kugeza kuri 9.2%, kandi amafaranga y’ubuzima bw’abarwayi mu gihe cy’umwaka umwe wo kwisuzumisha ashobora gutwara 60% y’umuryango winjiza. Abarwayi ba kanseri barwaye iyo ndwara kandi nanone bafite igitutu kinini mu bukungu.
Mirongo cyenda ku ijana yindwara ya kanseri yibara irashobora gukurwaho kubagwa, kandi uko ikibyimba kimaze kumenyekana, niko imyaka 5 yo kubaho nyuma yo kubagwa bikabije, ariko umubare rusange wongeye kugaruka nyuma yo kwangwa bikabije uracyari hafi 30%. Ikigereranyo cy’imyaka itanu yo kurwara kanseri yu mura mu baturage b’Ubushinwa ni 90.1%, 72,6%, 53.8% na 10.4% mu cyiciro cya I, II, III na IV.
Indwara nkeya zisigaye (MRD) nimpamvu nyamukuru itera kubyimba nyuma yo kuvurwa bikabije. Mu myaka yashize, ikoranabuhanga rya MRD ryerekana ibibyimba bikomeye ryateye imbere byihuse, kandi ubushakashatsi bwinshi bwo kureba no gutabara buremereye bwemeje ko imiterere ya MRD nyuma yo kubagwa ishobora kwerekana ibyago byo kongera kwibaruka kwa kanseri yibara. kwipimisha ctDNA bifite ibyiza byo kuba bidashoboka, byoroshye, byihuse, hamwe nurugero rwo hejuru rwo kugerwaho no gutsinda ibibyimba bitavutse.
Amabwiriza ya NCCN yo muri Amerika yerekeye kanseri y'amara hamwe n’amabwiriza ya CSCO yo mu Bushinwa kuri kanseri yu mura byombi avuga ko kugira ngo hamenyekane ingaruka ziterwa na oporisiyo nyuma yo guterwa no guhitamo imiti ivura kanseri y'amara, kwipimisha ctDNA bishobora gutanga amakuru ateganijwe kandi ateganijwe kugira ngo afashe mu byemezo bivura abarwayi bafite kanseri yo mu cyiciro cya II cyangwa III. Nyamara, ubushakashatsi bwinshi buriho bwibanda ku ihinduka rya ctDNA rishingiye ku ikoranabuhanga rikurikirana cyane (NGS), rifite inzira igoye, igihe kinini cyo kuyobora, hamwe n’igiciro kinini [3], hamwe no kutagira rusange muri rusange no kugaragara cyane mu barwayi ba kanseri.
Ku bijyanye n’icyiciro cya III abarwayi ba kanseri yibara, NGS ishingiye kuri ctDNA ikurikirana igura amadolari 10,000 yo gusura rimwe kandi bisaba igihe cyo gutegereza kugeza ibyumweru bibiri. Hamwe n'ikizamini cya methylation ya multigene muri ubu bushakashatsi, ColonAiQ®, abarwayi barashobora kugira ctDNA ikurikirana kuri kimwe cya cumi cyikiguzi bakabona raporo mugihe kitarenze iminsi ibiri.
Nk’uko bigaragara ku bantu 560.000 bashya ba kanseri ifata amara mu Bushinwa buri mwaka, abarwayi b’amavuriro cyane cyane barwaye kanseri yo mu cyiciro cya II-III (umubare ugereranyije ni 70%) bakeneye byihutirwa gukurikiranwa n’ingufu, noneho ingano y’isoko rya MRD igenzura rikomeye rya kanseri yibara igera kuri miliyoni z'abantu buri mwaka.
Birashobora kugaragara ko ibisubizo byubushakashatsi bifite akamaro gakomeye mubumenyi kandi bufatika. Binyuze mu bushakashatsi bunini bw’ubushakashatsi bw’amavuriro, bwemeje ko ikoranabuhanga rya PCR rishingiye ku maraso ctDNA multigene methylation methylation rishobora gukoreshwa mu guhanura kanseri y’indurwe no guhanura inshuro nyinshi hamwe no kumva neza, ku gihe ndetse no gukoresha amafaranga menshi, bigatuma imiti isobanutse neza igirira akamaro abarwayi ba kanseri benshi. Ubushakashatsi bushingiye kuri ColonAiQ®, ikizamini cya methylation ya gene nyinshi kuri kanseri yu mura cyakozwe na KUNY, agaciro kayo kavura mugupima hakiri kare no kwisuzumisha byemejwe n’ubushakashatsi bw’ubuvuzi bukuru.
Ikinyamakuru Gastroenterology (IF33.88), ikinyamakuru mpuzamahanga ku isonga mu bijyanye n’indwara zifata igifu mu 2021, cyatangaje ibyavuye mu bushakashatsi bwakozwe n’ibitaro bya Zhongshan byo muri kaminuza ya Fudan, ibitaro bya kanseri bya kaminuza ya Fudan hamwe n’ibindi bigo by’ubuvuzi byemewe bifatanije na KUNYAN Biologiya, byemeza ko byakozwe neza na ColonAiQ® ChangAiQ® mu gusuzuma no gusuzuma hakiri kare. gukurikirana prognoz ya kanseri yibara.

Kugirango turusheho kwemeza ikoreshwa rya ctDNA methylation mu byiciro by’ibyago, kuyobora ibyemezo byo kuvura no kugenzura hakiri kare kanseri yo mu cyiciro cya I-III, itsinda ry’ubushakashatsi ryarimo abarwayi 299 barwaye kanseri yo mu cyiciro cya I-III babazwe bikabije kandi bakusanya amaraso y’amaraso kuri buri cyiciro cyakurikiranwe (amezi atatu atandukanye) mu gihe cy’icyumweru kimwe mbere yo kubagwa, no mu gihe cyo kwipimisha amaraso.
Ubwa mbere, byagaragaye ko kwipimisha ctDNA bishobora guhanura ibyago byo kongera kugaruka ku barwayi ba kanseri yibara hakiri kare, haba mbere yo gutangira ndetse na nyuma yo kubagwa. Abarwayi ba ctDNA mbere yo gutangira bafite amahirwe menshi yo kugaruka nyuma yo kubagwa kurusha abarwayi ba ctDNA mbere yo gutangira (22.0%> 4.7%). Kwipimisha hakiri kare ctDNA kwipimisha biracyahanura ibyago byo kongera kubaho: ukwezi kumwe nyuma yo kwangwa bikabije, abarwayi ba ctDNA bafite amahirwe yo kugaruka inshuro 17.5 kurusha abarwayi babi; iryo tsinda ryasanze kandi ibizamini bya ctDNA na CEA byahinduye imikorere mike mu gutahura ibisubirwamo (AUC = 0.849), ariko itandukaniro ntabwo ryagaragaye cyane ugereranije na ctDNA (AUC = 0.839) kwipimisha byonyine Itandukaniro ntabwo ryari rinini ugereranije na ctDNA yonyine (AUC = 0.839).
Gutegura amavuriro hamwe n’ibintu bishobora guteza ingaruka kuri ubu ni byo shingiro ry’ibanze ry’ingaruka z’abarwayi ba kanseri, kandi muri paradizo iriho, umubare munini w’abarwayi baracyagaruka [4], kandi hakenewe byihutirwa ibikoresho byiza byo gutondekanya kuko kuvura birenze urugero no kutavurwa bibana mu ivuriro. Hashingiwe kuri ibi, itsinda ryashyize abarwayi bafite kanseri yo mu cyiciro cya III mu matsinda atandukanye hashingiwe ku gusuzuma ibyago byo kwisubiramo (ibyago byinshi (T4 / N2) hamwe n’ibyago bike (T1-3N1)) hamwe n’igihe cyo kuvura (amezi 3/6). Isesengura ryagaragaje ko abarwayi bo mu itsinda ry’ibyago byinshi by’abarwayi ba ctDNA bafite amahirwe make yo kwisubiramo iyo bahawe amezi atandatu yo kuvura; mu matsinda mato mato y’abarwayi ba ctDNA, nta tandukaniro rikomeye ryabaye hagati yinzira yo kuvura hamwe n’ibisubizo by’abarwayi; mugihe abarwayi ba ctDNA-mbi bari bafite prognoza nziza cyane kurusha abarwayi ba ctDNA hamwe nigihe kirekire nyuma yo kubagwa (RFS); icyiciro cya I hamwe na kanseri yo mu cyiciro cya II kanseri yibara Abarwayi bose ba ctDNA-mbi ntibongeye kubaho mumyaka ibiri; Kubwibyo rero, guhuza ctDNA hamwe nubuvuzi byitezwe ko bizarushaho kunonosora ibyiciro no guhanura neza ko bizongera kubaho.

Igicapo 1. Isesengura rya plasma ctDNA kuri POM1 kugirango hamenyekane hakiri kare kanseri yibara
Ibindi bisubizo by’ibizamini bya ctDNA byerekanaga ko ibyago byo kwisubiramo byari byinshi cyane ku barwayi bafite ibizamini byiza bya ctDNA kurusha abarwayi bafite ctDNA mbi mu gihe cyo gukurikirana indwara nyuma yo kuvurwa neza (nyuma yo kubagwa bikabije + bivura imiti ivura indwara) (Ishusho ya 3ACD), kandi ko ctDNA ishobora kwerekana ko ibibyimba byongeye kubaho mbere y'amezi 20 mbere yo kwerekanwa hakiri kare (Ishusho 3B).

Igishushanyo 2. CtDNA isesengura rishingiye kuri cohort ndende kugirango tumenye kanseri yibara

Ati: "Umubare munini w’ubuvuzi bw’ubuhinduzi muri kanseri yu mura uyobora iyo disipuline, cyane cyane ibizamini bya MRD bishingiye kuri ctDNA byerekana ubushobozi bukomeye bwo kuzamura imiyoborere y’abarwayi ba kanseri yibasira kanseri nyuma yo kubagwa, hashobora kubaho ibyemezo by’ubuvuzi ndetse no gukurikirana hakiri kare.

Ibyiza byo guhitamo methylation ya ADN nk'ikimenyetso gishya cya MRD hejuru yo kumenya ihinduka ry’imihindagurikire y’imiterere ni uko bidasaba ko hakurikiranwa genome ikurikiranye yerekana ibibyimba by’ibibyimba, ikoreshwa mu buryo butaziguye mu gupima amaraso, kandi ikirinda ibisubizo byiza biturutse ku kumenya ihinduka ry’imiterere ihindagurika ikomoka ku ngingo zisanzwe, indwara nziza, na hematopoiesis ya clon.
Ubu bushakashatsi hamwe n’ubundi bushakashatsi bujyanye na bwo bwemeza ko kwipimisha kwa MRD bishingiye kuri ctDNA ari cyo kintu cy’ingenzi cyigenga cy’ingaruka ziterwa no kongera kwandura kanseri yo mu cyiciro cya I-III kandi gishobora gukoreshwa mu gufasha gufata ibyemezo byo kuvura, harimo “escalation” na “kumanura” imiti ivura indwara ya MRD nicyo kintu gikomeye cyigenga gishobora kubaho nyuma yo kubagwa kanseri yo mu cyiciro cya I-III.
Umwanya wa MRD urimo uratera imbere byihuse hamwe nibintu byinshi bishya, byunvikana cyane kandi byihariye bishingiye kuri epigenetics (ADN methylation na fragmentomics) na genomics (ultra-deep target sequening or genome sequening). Turateganya ko ColonAiQ® ikomeje gutegura ubushakashatsi bunini bw’amavuriro kandi ishobora kuba ikimenyetso gishya cy’ibizamini bya MRD bihuza uburyo bworoshye, imikorere ihanitse kandi ihendutse kandi ishobora gukoreshwa cyane mu bikorwa by’ubuvuzi bisanzwe. ”
Reba
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