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 bya kaminuza ya Fudan na Prof. Wang Jing wo mu bitaro bya Renji byo mu ishuri ry’ubuvuzi rya kaminuza ya Shanghai Jiao Tong, muri ubufatanye na KUNYUAN BIOLOGY: “Kumenya hakiri kare Indwara Zisigara Zifata Indwara no Gutandukana kw'Icyiciro cya Kanseri yo mu cyiciro cya mbere kugeza ku cya gatatu binyuze mu kuzenguruka Tumor ADN Methylation na Risk Stratification) ”. Ubu bushakashatsi nubushakashatsi bwa mbere bwibanze ku isi bwifashishije ikoranabuhanga rya PCR rishingiye ku maraso ctDNA multigene methylation tekinoroji yo guhanura kanseri yibara no guhanura inshuro nyinshi, itanga inzira ya tekiniki ihendutse kandi ikemurwa ugereranije nuburyo bukoreshwa bwa tekinoroji ya MRD, biteganijwe. kunoza cyane imikoreshereze yubuvuzi bwa kanseri yibara no guhanura no guhanura, no kuzamura cyane ubuzima bwumurwayi nubuzima bwiza. 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%. Abarenga 80% by'abarwayi 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 imibereho n'imibereho ikomeye mu bukungu umutwaro. 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 gufata 60% bya amafaranga yinjira mu muryango. Abarwayi ba kanseri barwaye iyo ndwara kandi nanone bafite igitutu kinini cy'ubukungu [2].
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 nicyitegererezo kinini cyo 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 ateganya kugira ngo afashe mu byemezo bivura abarwayi bafite icyiciro cya II cyangwa kanseri y'amara ya 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 banduye kanseri ifata amara mu Bushinwa buri mwaka, abarwayi b’amavuriro cyane cyane barwaye kanseri yo mu cyiciro cya II-III (umubare uri hafi 70%) bakeneye byihutirwa gukurikiranwa n’ingufu, hanyuma ingano y’isoko rya MRD ikurikirana ikurikirana. kanseri yibara igera kuri miriyoni yabantu buri mwaka.
Birashobora kugaragara ko ibisubizo byubushakashatsi bifite akamaro gakomeye mubumenyi nibikorwa bifatika. Binyuze mu bushakashatsi bunini bw’ubushakashatsi bw’amavuriro, bwemeje ko ikoranabuhanga ry’amaraso rya PCR rishingiye ku maraso ctDNA multigene methylation rishobora gukoreshwa mu guhanura kanseri y’ibara no guhanura inshuro nyinshi hamwe no gukangurira abantu, igihe, 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 cya mbere 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 n’ibindi bigo by’ubuvuzi byemewe bifatanije na KUNYAN Biologiya, byemeza imikorere myiza ya ColonAiQ® ChangAiQ® mugupima hakiri kare no gusuzuma hakiri kare kanseri yibara, hanyuma ikabanza gukora ubushakashatsi I nayo ishakisha uburyo bushobora gukoreshwa muri gukurikirana prognoza ya kanseri yibara.

Kugirango turusheho kwemeza ikoreshwa rya ctDNA methylation mu byiciro, ibyago byo kuvura no gukurikirana 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 ku buri ngingo ikurikiranwa (amezi atatu atandukanye) mugihe cyicyumweru kimwe mbere yo kubagwa, ukwezi kumwe nyuma yo kubagwa, no mubuvuzi bwa nyuma yubuvuzi bwo kuvura amaraso ya ctDNA.
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 byateje imbere imikorere mike mugushakisha uko byagaruka (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).
Gutunganya 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 nko kuvura birenze urugero kandi 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 bya ctDNA bifite imbaraga kurusha abarwayi bafite ctDNA mbi mu cyiciro cyo gukurikirana indwara nyuma yo kuvurwa neza (nyuma yo kubagwa bikabije + bivura imiti) (Ishusho 3ACD), kandi ko ctDNA ishobora kwerekana ibibyimba byongeye kugaruka mbere y'amezi 20 mbere yo gufata amashusho (Ishusho 3B), bitanga amahirwe yo gutahura hakiri kare indwara zongera kubaho no gutabara mugihe.

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 nkibimenyetso bishya bya 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 bisanzwe tissue, indwara nziza, na hematopoiesis ya clon.
Ubu bushakashatsi hamwe n’ubundi bushakashatsi bujyanye na bwo bwemeza ko kwipimisha MRD bishingiye kuri ctDNA ari byo bintu by’ingenzi byigenga byongera kwandura kanseri yo mu cyiciro cya I-III kandi bishobora gukoreshwa mu gufasha gufata ibyemezo byo kuvura, harimo “escalation” na “kumanura” imiti ivura indwara. MRD nicyo kintu cyingenzi cyigenga gishobora kwisubiramo 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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[2] “Umutwaro w'indwara ya kanseri yibara mu baturage b'Abashinwa: yahindutse mu myaka yashize? , Ikinyamakuru cyo mu Bushinwa cya Epidemiologiya, Vol. 41, No 10, Ukwakira 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, n'abandi. Intego yibisekuruza bizakurikiraho bikwirakwiza-ibibyimba ADN yo gukurikirana indwara nkeya zisigaye muri kanseri yumura. Ann Oncol. 1 Ugushyingo 2019; 30 (11): 1804-1812.
[4] Taieb J, André T, Auclin E. Gutunganya imiti ivura kanseri yumura itari metastatike, amahame mashya nibitekerezo. Kuvura Kanseri Ibyah. 2019; 75: 1-11.