Inyigo y’ubushakashatsi iteganyijwe: Ikoranabuhanga rya PCR-based blood ctDNA methylation ryafunguye igihe gishya cyo kugenzura MRD ku ndwara ya kanseri y’inkondo y’umura

Vuba aha, JAMA Oncology (IF 33.012) yasohoye ibyavuye mu bushakashatsi bw'ingenzi [1] bwakozwe n'ikipe ya Porofeseri Cai Guo-ring wo mu bitaro bya Kanseri bya Kaminuza ya Fudan na Porofeseri Wang Jing wo mu bitaro bya Renji byo mu ishuri ry'ubuvuzi rya Kaminuza ya Shanghai Jiao Tong, ku bufatanye na KUNYUAN BIOLOGY: “Gutahura hakiri kare indwara zisigaye za molekile no gushyira mu byiciro ibyago byo kwandura kanseri y'inkondo y'umura ku cyiciro cya mbere kugeza kuri gatatu binyuze mu kuzenguruka ADN ya Kanseri n'ishyirwa mu byiciro ry'ibyago)”. Ubu bushakashatsi ni bwo bushakashatsi bwa mbere ku isi bushingiye ku bigo byinshi bukoresha ikoranabuhanga rya PCR-based blood ctDNA multigene methylation mu gupima no kugenzura kanseri y'inkondo y'umura ku gipimo cyo kwandura no kugenzura ko yakongera kwandura, butanga inzira ya tekiniki n'igisubizo gihendutse ugereranije n'uburyo bwa MRD busanzweho, byitezwe ko buzongera cyane ikoreshwa ry'ubuvuzi mu gupima no gukurikirana ko yakongera kwandura kanseri y'inkondo y'umura, kandi bunoze cyane ubuzima bw'umurwayi n'ireme ry'ubuzima bwe. Ubushakashatsi bwasuzumwe cyane n'ikinyamakuru n'abanditsi bacyo, kandi bwashyizwe ku rutonde rw'inyandiko z'ingenzi zisaba ubufasha muri iki kinyamakuru, kandi Porofeseri Juan Ruiz-Bañobre wo muri Esipanye na Porofeseri Ajay Goel wo muri Leta Zunze Ubumwe za Amerika batumiwe kubusuzuma. Ubu bushakashatsi bwatangajwe kandi na GenomeWeb, ikigo gikomeye cy’itangazamakuru ry’ubuvuzi muri Leta Zunze Ubumwe za Amerika.

Kanseri y'inkondo y'umura (CRC) ni ikibyimba gisanzwe cy'inzira y'igifu mu Bushinwa. Amakuru y'Ikigo Mpuzamahanga gishinzwe Ubushakashatsi kuri Kanseri (IARC) yo mu 2020 agaragaza ko abarwayi bashya 555.000 mu Bushinwa bangana na 1/3 cy'isi, aho igipimo cy'abandura kizamuka kikagera ku mwanya wa kabiri wa kanseri isanzwe mu Bushinwa; impfu 286.000 zigize 1/3 cy'isi, zikaba ari zo za gatanu zikunze gutera impfu za kanseri mu Bushinwa. Impamvu ya gatanu y'impfu mu Bushinwa. Ni ngombwa kumenya ko mu barwayi basuzumwe, icyiciro cya mbere, icya kabiri, icya gatatu na cya kane cya TNM kiri kuri 18.6%, 42.5%, 30.7% na 8.2% uko bikurikirana. Abarenga 80% by'abarwayi bari mu cyiciro cyo hagati n'icya nyuma, kandi 44% byabo bafite indwara ya metastases igana ku mwijima no mu bihaha icyarimwe cyangwa idasanzwe, bigira ingaruka zikomeye ku gihe cyo kubaho, bigashyira ubuzima bw'abaturage bacu mu kaga kandi bigatera umutwaro ukomeye mu mibereho no mu bukungu. Dukurikije imibare y’Ikigo cy’Igihugu gishinzwe kurwanya kanseri, izamuka ry’ikiguzi cyo kuvura kanseri y’inkondo y’umura mu Bushinwa buri mwaka riri hagati ya 6.9% na 9.2%, kandi amafaranga akoreshwa mu kwivuza ku barwayi mu mwaka umwe nyuma yo kurwara kanseri ashobora gufata 60% by’amafaranga yinjizwa n’umuryango. Abarwayi ba kanseri barwaye iyi ndwara kandi bafite igitutu gikomeye cy’ubukungu [2].
Mirongo icyenda ku ijana by'ibisebe bya kanseri y'inkondo y'umura bishobora gukurwaho mu buryo bwo kubaga, kandi uko ikibyimba kigaragara kare, niko umubare w'abakiriho nyuma yo kubagwa mu buryo bw'ingufu uzamuka mu myaka itanu, ariko igipimo rusange cyo kongera kugaragara nyuma yo kubagwa mu buryo bw'ingufu kiracyari hafi 30%. Igipimo cy'imyaka itanu cyo kubaho kwa kanseri y'inkondo y'umura mu baturage b'Abashinwa ni 90.1%, 72.6%, 53.8% na 10.4% ku cyiciro cya I, II, III na IV.
Indwara ntoya zisigara (MRD) niyo mpamvu ikomeye ituma ikibyimba kigaruka nyuma yo kuvurwa cyane. Mu myaka ya vuba aha, ikoranabuhanga rya MRD ryo gupima ibibyimba bikomeye ryateye imbere cyane, kandi ubushakashatsi bwinshi bw’isuzuma n’isuzuma ry’ibanze bwemeje ko MRD nyuma yo kubagwa ishobora kugaragaza ibyago byo kongera kurwara kanseri y’inkondo y’umura nyuma yo kubagwa. Gupima ctDNA bifite ibyiza byo kuba bidatera kanseri, byoroshye, byihuse, hamwe n’ibipimo byinshi byo kuvura ikibyimba no gutsinda ubudasa bw’ikibyimba.
Amabwiriza ya NCCN yo muri Amerika ku ndwara ya kanseri y'inkondo y'umura n'amabwiriza ya CSCO yo mu Bushinwa ku ndwara ya kanseri y'inkondo y'umura yombi avuga ko kugira ngo hamenyekane ingaruka zo kongera kubaho nyuma yo kubagwa no guhitamo imiti ivura kanseri y'inkondo y'umura, gupima ctDNA bishobora gutanga amakuru ajyanye no guhanura no gutanga amakuru ajyanye no guhanura kugira ngo bifashe mu gufata ibyemezo by'ubuvuzi bw'inyongera ku barwayi ba kanseri y'inkondo y'umura yo mu cyiciro cya kabiri cyangwa icya gatatu. Ariko, ubushakashatsi bwinshi buriho bwibanda ku mpinduka za ctDNA zishingiye ku ikoranabuhanga ryo gukurikirana imikorere ya kanseri (NGS), rifite inzira igoye, rimara igihe kirekire, kandi rihenze cyane [3], hamwe no kutagira uburyo bwo kuvura kanseri mu buryo busanzwe kandi hakiri bake mu barwayi ba kanseri.
Ku bijyanye n'abarwayi ba kanseri y'inkondo y'umura yo mu cyiciro cya gatatu, igenzura ry'imikorere ya ctDNA rishingiye kuri NGS ritwara amadorari 10.000 ku nshuro imwe kandi risaba igihe cyo gutegereza kugeza ku byumweru bibiri. Hamwe n'ikizamini cya multigene methylation muri ubu bushakashatsi, ColonAiQ®, abarwayi bashobora gukurikirana imikorere ya ctDNA ku giciro cya cumi cy'ikiguzi kandi bakabona raporo mu minsi ibiri gusa.
Dukurikije abarwayi bashya 560.000 ba kanseri y'inkondo y'umura mu Bushinwa buri mwaka, abarwayi benshi barwaye kanseri y'inkondo y'umura yo mu cyiciro cya kabiri kugeza icya gatatu (ikigero ni hafi 70%) bafite icyifuzo cyihutirwa cyo gukurikiranwa mu buryo bwihuse, hanyuma ingano y'isoko ry'igenzura rya MRD rijyanye na kanseri y'inkondo y'umura ikagera ku bantu babarirwa muri za miriyoni buri mwaka.
Bigaragara ko ibyavuye mu bushakashatsi bifite akamaro kanini mu bya siyansi no mu buryo bufatika. Binyuze mu bushakashatsi bunini bw’ubuvuzi, byemeje ko ikoranabuhanga rya PCR-based blood ctDNA multigene methylation rishobora gukoreshwa mu guhanura isubiramo rya kanseri y’inkondo y’umura no kugenzura isubiramo ryayo haba mu buryo bw’ubushishozi, ku gihe no mu buryo bwiza, bigatuma imiti ijyanye n’ibizamini ifasha abarwayi benshi ba kanseri. Ubu bushakashatsi bushingiye kuri ColonAiQ®, ikizamini cya multigene methylation cyakozwe na KUNY, agaciro kacyo mu gusuzuma no gusuzuma kare kakemezwa n’ubushakashatsi bw’ubuvuzi busanzwe.
Gastroenterology (IF33.88), ikinyamakuru mpuzamahanga gikomeye mu bijyanye n'indwara z'igifu mu 2021, cyatangaje ibyavuye mu bushakashatsi bw’ibitaro bya Zhongshan bya Kaminuza ya Fudan, Ibitaro bya Kanseri bya Kaminuza ya Fudan n'ibindi bigo by’ubuvuzi byemewe bifatanyije na KUNYAN Biological, byemezaga imikorere myiza ya ColonAiQ® ChangAiQ® mu gusuzuma hakiri kare kanseri y'inkondo y'umura, ndetse banasuzuma mbere na mbere. Nanone isuzuma uburyo ishobora gukoreshwa mu gukurikirana kanseri y'inkondo y'umura.

Kugira ngo hamenyekane neza ikoreshwa rya methylation ya ctDNA mu gutandukanya ibyago, hagafatwa ingamba zo kuvura no gukurikirana hakiri kare kanseri y’inkondo y’umura icyiciro cya mbere kugeza icya gatatu, itsinda ry’ubushakashatsi ryari rigizwe n’abarwayi 299 barwaye kanseri y’inkondo y’umura icyiciro cya mbere kugeza icya gatatu babazwe cyane kandi bagakusanya amaraso kuri buri gice cyo gukurikirana (amezi atatu atandukanye) mu cyumweru kimwe mbere yo kubagwa, ukwezi kumwe nyuma yo kubagwa, no mu buvuzi bufasha nyuma yo kubagwa kugira ngo hasuzumwe ctDNA mu maraso.
Ubwa mbere, byagaragaye ko gupima ctDNA bishobora guhanura ibyago byo kongera kugaragara ku barwayi ba kanseri y'inkondo y'umura hakiri kare, haba mbere yo kubagwa ndetse no mu ntangiriro ya nyuma yo kubagwa. Abarwayi ba ctDNA mbere yo kubagwa bari bafite amahirwe menshi yo kongera kugaragara nyuma yo kubagwa ugereranije n'abarwayi ba ctDNA mbere yo kubagwa (22.0% > 4.7%). Gupima ctDNA mbere yo kubagwa byagaragaje ko bishobora kongera kugaragara: ukwezi kumwe nyuma yo kubagwa cyane, abarwayi ba ctDNA bari bafite amahirwe menshi yo kongera kugaragara inshuro 17.5 ugereranyije n'abarwayi banduye; itsinda ryasanze kandi ko gupima ctDNA na CEA byazamuye gato imikorere mu kumenya kongera kugaragara (AUC = 0.849), ariko itandukaniro ntiryari rinini ugereranije n'ibizamini bya ctDNA (AUC = 0.839) gusa. Itandukaniro ntiryari rinini ugereranije na ctDNA yonyine (AUC = 0.839).
Guteranya ubuvuzi hamwe n’ibintu bishobora gutera ibyago ni byo shingiro ry’ingenzi mu gushyira mu byiciro ibyago abarwayi ba kanseri, kandi muri gahunda iriho ubu, umubare munini w’abarwayi uracyagaruka [4], kandi hakenewe byihutirwa ibikoresho byiza byo gushyira mu byiciro kuko ubuvuzi burenze urugero n’ubuvuzi budahagije buriho mu ivuriro. Hashingiwe kuri ibi, itsinda ryashyize abarwayi ba kanseri y’inkondo y’umura mu byiciro bitandukanye hashingiwe ku isuzuma ry’ibyago byo gusubira mu buvuzi (ibyago byinshi (T4/ N2) n’ibyago bike (T1-3N1)) n’igihe cyo kuvurwa gifasha (amezi 3/6). Isesengura ryagaragaje ko abarwayi bari mu itsinda ry’abarwayi bafite ibyago byinshi byo gusubira mu buvuzi bafite igipimo gito cyo gusubira mu buvuzi iyo bahawe imiti y’inyongera mu mezi atandatu; mu itsinda ry’abarwayi bafite ibyago bike byo gusubira mu buvuzi, nta tandukaniro rinini ryari riri hagati y’uburyo bwo kuvurwa n’umurwayi butanga ubufasha n’ibyavuye mu buvuzi; mu gihe abarwayi bafite ibyago bike byo gusubira mu buvuzi bwa ctDNA bari bafite imiterere myiza cyane kurusha abarwayi bafite ctDNA kandi igihe kirekire nyuma yo kubagwa kidasubira mu buvuzi (RFS); Icyiciro cya mbere n'icya kabiri cy'indwara ya kanseri y'inkondo y'umura. Abarwayi bose badafite ctDNA ntibagarutse mu myaka ibiri; bityo, guhuza ctDNA n'ibimenyetso by'ubuvuzi byitezweho kunoza uburyo bwo gushyira mu byiciro ibyago no kumenya neza uko bizagaruka.

Ishusho ya 1. Isesengura rya plasma ctDNA kuri POM1 kugira ngo hamenyekane hakiri kare ko kanseri y'inkondo y'umura ishobora kongera kugaruka
Ibindi bisubizo by’ibizamini bya ctDNA byagaragaje ko ibyago byo kongera kugaruka byari byinshi cyane ku barwayi bafite ibizamini bya ctDNA bifatika kurusha abarwayi bafite ctDNA mbi mu gihe cyo gukurikirana isubira ry’indwara nyuma yo kuvurwa burundu (nyuma yo kubagwa cyane + ubuvuzi bw’inyongera) (Ishusho ya 3ACD), kandi ko ctDNA ishobora kugaragaza ko ikibyimba gishobora kongera kugaruka mu mezi 20 mbere y’uko gifatwa (Ishusho ya 3B), bitanga amahirwe yo kumenya hakiri kare ko indwara ishobora kongera kugaruka no gutabara ku gihe.

Ishusho ya 2. Isesengura rya ctDNA rishingiye ku itsinda ry’abantu barwaye kanseri y’inkondo y’umura (longitudinal cohort) kugira ngo harebwe uko kanseri y’inkondo y’umura isubira kugaruka

“Inyigo nyinshi z’ubuvuzi bushingiye ku guhindura imiterere y’umubiri muri kanseri y’inkondo y’umura ziyobora urwo bumenyi, cyane cyane ibizamini bya MRD bishingiye kuri ctDNA bigaragaza ubushobozi bukomeye bwo kunoza imicungire y’abarwayi ba kanseri y’inkondo y’umura nyuma yo kubagwa binyuze mu gutuma habaho ibyiciro by’ibyago byo gusubira inyuma, kuyobora ibyemezo byo kuvura no gukurikirana hakiri kare uko gusubira inyuma bisubira.”

Akamaro ko guhitamo methylation ya ADN nk'ikimenyetso gishya cya MRD kuruta gupima impinduka mu mubiri ni uko idasaba gusuzuma imiterere ya genome yose y'uturemangingo tw'ikibyimba, ikoreshwa mu buryo butaziguye mu gupima amaraso, kandi ikirinda ibisubizo bitari byo bitewe no kumenya impinduka mu mubiri zikomoka ku ngingo zisanzwe, indwara zitari mbi, no mu maraso ya clonal.
Ubu bushakashatsi n'ubundi bushakashatsi bufitanye isano byemeza ko ikizamini cya MRD gishingiye kuri ctDNA ari cyo kintu cy'ingenzi cyane gishobora gutuma kanseri y'inkondo y'umura isubira ku cyiciro cya I-III kandi gishobora gukoreshwa mu gufasha gufata ibyemezo byo kuvura, harimo "kwiyongera" no "kugabanya" uburyo bwo kuvura bufasha. MRD ni cyo kintu cy'ingenzi cyane gishobora gutuma kanseri y'inkondo y'umura isubira ku cyiciro cya I-III.
Urwego rwa MRD rurimo gutera imbere vuba hamwe n’ibizamini byinshi bishya, by’umwihariko kandi byihariye bishingiye kuri epigenetics (methylation ya ADN na fragmentomics) na genomics (sequencing ya ultra-deep targeted cyangwa sequencing ya genome yose). Twiteze ko ColonAiQ® ikomeje gutegura inyigo nini z’ubuvuzi kandi ishobora kuba ikimenyetso gishya cy’ibizamini bya MRD bihuza uburyo bworoshye bwo kubigeraho, imikorere myiza n’ubushobozi bwo kubikoresha kandi bishobora gukoreshwa cyane mu buvuzi busanzwe.”
Amareferensi
[1] Mo S, Ye L, Wang D, Han L, Zhou S, Wang H, Dai W, Wang Y, Luo W, Wang R, Xu Y, Cai S, Liu R, Wang Z, Cai G. Gutahura hakiri kare indwara zisigaye za molekile no gushyira mu byiciro ibyago byo kwandura kanseri y'inkondo y'umura kuva ku cyiciro cya mbere kugeza kuri gatatu binyuze muri Methylation ya ADN ya kanseri izenguruka. JAMA Oncol. 2023 Mata 20.
[2] “Umutwaro w’indwara ya kanseri y’inkondo y’umura mu baturage b’Abashinwa: ese warahindutse mu myaka ya vuba aha? , Ikinyamakuru cy’Abashinwa cy’Indwara z’Ubworozi, Vol. 41, No. 10, Ukwakira 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, n'abandi. Yibanze ku ikurikiranwa rya ADN y'ikibyimba gikwirakwira mu gisekuru gikurikira kugira ngo hakurikiranwe indwara nke zisigaye muri kanseri y'amara. Ann Oncol. 1 Ugushyingo 2019;30(11):1804-1812.
[4] Taieb J, André T, Auclin E. Kuvugurura uburyo bwo kuvura kanseri y'amara idatera kanseri, amahame mashya n'ibitekerezo bishya. Cancer Treat Rev. 2019; 75: 1-11.