ʻO ka haʻawina holomua holomua: wehe ʻia ka ʻenehana methylation ctDNA methylation koko PCR i kahi manawa hou o ka nānā ʻana MRD no ka maʻi maʻi colorectal

I kēia mau lā, JAMA Oncology (IF 33.012) i hoʻopuka i kahi hopena noiʻi koʻikoʻi [1] e ka hui o Prof. Cai Guo-ring mai Cancer Hospital o Fudan University a me Prof. Wang Jing mai Renji Hospital o Shanghai Jiao Tong University School of Medicine, ma hui pū me KUNYUAN BIOLOGY: "Ka ʻike mua ʻana o ka maʻi ʻokoʻa Molecular a me ka Stratification Risk for Stage I a i ka III Colorectal Cancer ma o ka Circulating Tumor DNA Methylation a me ka Stratification Risk). ʻO kēia haʻawina ʻo ia ka noiʻi multicenter mua loa ma ka honua e hoʻohana i ka ʻenehana PCR-based blood ctDNA multigene methylation no ka wānana ʻana i ka maʻi maʻi ʻaʻai kala a me ka nānā hou ʻana, e hāʻawi ana i kahi ala ʻenehana ʻoi aku ka maikaʻi a me ka hopena i hoʻohālikelike ʻia me nā ʻano ʻenehana ʻike MRD i loaʻa, i manaʻo ʻia. e hoʻomaikaʻi maikaʻi i ka hoʻohana ʻana i ka maʻi maʻi colorectal ka wānana a me ka nānā ʻana, a hoʻomaikaʻi nui i ke ola o ka maʻi a me ka maikaʻi o ke ola. Ua loiloi nui ʻia ke aʻo ʻana e ka puke pai a me kāna mau mea hoʻoponopono, a ua helu ʻia ma ke ʻano he pepa manaʻo nui ma kēia pukana, a ua kono ʻia ʻo Polofesa Juan Ruiz-Bañobre mai Sepania a me Profesor Ajay Goel mai ʻAmelika Hui Pū ʻIa e nānā iā ia. Ua hōʻike pū ʻia ke aʻo ʻana e GenomeWeb, kahi media biomedical alakaʻi ma United States.

ʻO ka maʻi ʻaʻai ʻokoʻa (CRC) kahi maʻi maʻi maʻamau o ka ʻōpū ʻōpū ma Kina. Hōʻike ka ʻikepili 2020 International Agency for Research on Cancer (IARC) he 555,000 mau hihia hou ma Kina e pili ana ma kahi o 1/3 o ka honua, me ka piʻi ʻana o ka maʻi i ka lua o nā maʻi maʻi maʻamau ma Kina; ʻO 286,000 mau make ma kahi o 1/3 o ka honua, ka helu ʻana ʻo ka lima o ke kumu maʻamau o ka make maʻi kanesa ma Kina. ʻO ke kumu ʻelima o ka make ma Kina. He mea nui ia ma waena o nā mea maʻi i ʻike ʻia, ʻo nā pae TNM I, II, III a me IV he 18.6%, 42.5%, 30.7% a me 8.2%. ʻOi aku ma mua o 80% o nā mea maʻi i ka waena a me ka hopena hope, a ʻo 44% o lākou he metastases like ʻole a heterochronic mamao i ka ate a me ka māmā, e hoʻopilikia koʻikoʻi i ke ola ola, e hoʻoweliweli i ke olakino o ko mākou poʻe noho a hoʻoulu i ka pilikanaka a me ka hoʻokele waiwai. kaumaha. Wahi a nā helu helu o ka National Cancer Center, ʻo ka piʻi ʻana o ka makahiki ma ke kumukūʻai o ka mālama ʻana i ka maʻi maʻi colorectal ma Kina ma kahi o 6.9% a 9.2%, a ʻo ka hoʻolilo ola kino o nā mea maʻi i loko o hoʻokahi makahiki o ka maʻi maʻi hiki ke piʻi i 60% o ka loaʻa kālā ʻohana. ʻO ka poʻe maʻi maʻi maʻi e loaʻa ana i ka maʻi a ma lalo o ke kaomi waiwai nui [2].
He kanaiwa pākēneka o nā maʻi maʻi maʻi colorectal hiki ke hoʻoneʻe ʻia me ka ʻokiʻoki, a ʻo ka mua o ka ʻike ʻia ʻana o ke koko, ʻoi aku ka kiʻekiʻe o ka helu ola ʻelima mau makahiki ma hope o ka hoʻokaʻawale ʻana i ka ʻokiʻoki, akā ʻo ka nui o ka hoʻi hou ʻana ma hope o ka wehe ʻana o ka radical ma kahi o 30%. He 90.1%, 72.6%, 53.8% a me 10.4% no ka pae I, II, III a me IV o na makahiki he elima makahiki o ka ma'i kanesa colorectal.
ʻO ka maʻi koena liʻiliʻi (MRD) kahi kumu nui o ka hoʻi hou ʻana o ka maʻi ma hope o ka mālama ʻana. I nā makahiki i hala iho nei, ua holomua ka ʻenehana ʻike MRD no nā maʻi koko paʻa, a ua hōʻoia kekahi mau haʻawina ʻike kaumaha a me nā haʻawina interventional hiki i ke kūlana MRD postoperative ke hōʻike i ka pilikia o ka hoʻi hou ʻana o ka maʻi maʻi colorectal. Loaʻa i ka hoʻāʻo ctDNA ka maikaʻi o ka noninvasive, maʻalahi, wikiwiki, me ke kiʻekiʻe kiʻekiʻe o ka laʻana a me ka lanakila ʻana i ka heterogeneity tumor.
ʻO nā alakaʻi alakaʻi o ka US NCCN no ka maʻi maʻi ʻaʻai a me nā alakaʻi CSCO Kina no ka maʻi maʻi colorectal ʻelua ʻōlelo ʻelua no ka hoʻoholo ʻana i ka pilikia o ka hoʻi hou ʻana o ka postoperative a me ke koho ʻana i ka chemotherapy adjuvant i ka maʻi maʻi colon, hiki i ka hoʻāʻo ctDNA ke hāʻawi i ka ʻike wānana a me ka wānana e kōkua i nā hoʻoholo hoʻoholo lapaʻau adjuvant no nā maʻi me ka pae II. a i ʻole III ka maʻi ʻaʻai koko. Eia nō naʻe, ʻo ka hapa nui o nā haʻawina e pili ana i nā mutations ctDNA e pili ana i ka ʻenehana sequencing kiʻekiʻe (NGS), he kaʻina hana paʻakikī, lōʻihi ka manawa alakaʻi, a me ke kumukūʻai kiʻekiʻe [3], me ka nele iki o ka generalizability a me ka haʻahaʻa haʻahaʻa ma waena o nā maʻi maʻi maʻi.
Ma ka hihia o nā maʻi maʻi maʻi colorectal stage III, ʻo NGS-based ctDNA dynamic monitoring koina a hiki i $10,000 no ka kipa hoʻokahi a koi ʻia kahi manawa kali a hiki i ʻelua pule. Me ka ho'āʻo multigene methylation i loko o kēia haʻawina, ColonAiQ®, hiki i nā maʻi ke loaʻa ka nānā ʻana i ka ctDNA ikaika ma ka hapaʻumi o ke kumukūʻai a loaʻa i kahi hōʻike i loko o ʻelua mau lā.
Wahi a ka 560,000 mau hihia hou o ka maʻi maʻi colorectal ma Kina i kēlā me kēia makahiki, ʻo ka poʻe maʻi maʻi maʻi me ka maʻi maʻi colorectal stage II-III (ʻo ka hapa he 70%) ʻoi aku ka nui o ka noi no ka nānā ʻana i ka ikaika, a laila ka nui o ka mākeke o ka MRD dynamic monitoring. ʻO ka maʻi kanesa colorectal hiki i nā miliona o nā kānaka i kēlā me kēia makahiki.
Hiki ke ʻike ʻia he koʻikoʻi ko nā hualoaʻa noiʻi koʻikoʻi i ka ʻepekema a me ka hana. Ma o ka nui-scale prospective clinical studies, ua hōʻoia i ka PCR-based blood ctDNA multigene methylation technology hiki ke hoʻohana no ka colorectal cancer recurrence prediction a me ka nānā hou ʻana me ka naʻau, ka manawa a me ka uku-pono, ʻoi aku ka maikaʻi o ka lāʻau lapaʻau kūpono e pōmaikaʻi ai i nā maʻi maʻi maʻi. . Hoʻokumu ʻia ke aʻo ʻana ma ColonAiQ®, kahi hoʻāʻo methylation multi-gene no ka maʻi maʻi colorectal i hoʻomohala ʻia e KUNY, nona ka waiwai hoʻohana lapaʻau i ka nānā mua ʻana a me ka hōʻoia ʻana i hōʻoia ʻia e kahi noiʻi lapaʻau koʻikoʻi.
ʻO Gastroenterology (IF33.88), ka puke pai honua kiʻekiʻe ma ke kahua o nā maʻi gastrointestinal ma 2021, i hōʻike i nā hopena noiʻi multicenter o Zhongshan Hospital o Fudan University, Cancer Hospital o Fudan University a me nā keʻena olakino mana ʻē aʻe i hui pū me KUNYAN Biological, i hōʻoia ʻia. ʻO ka hana maikaʻi loa o ColonAiQ® ChangAiQ® i ka nānā mua ʻana a me ka ʻike mua ʻana o ka maʻi maʻi colorectal, a ua ʻimi mua ʻo ia i ka hoʻohana ʻana. i ka nānā ʻana i ka wānana o ka maʻi maʻi colorectal.

No ka hōʻoia hou ʻana i ka noi ʻana o ka ctDNA methylation i ka stratification pilikia, ke alakaʻi ʻana i nā hoʻoholo lapaʻau a me ka nānā mua ʻana i ka wā I-III colorectal cancer, ua komo ka hui noiʻi i 299 mau mea maʻi me ka pae I-III colorectal cancer i hana ʻia i ka hōʻoki radical a hōʻiliʻili i nā hōʻailona koko ma ʻO kēlā me kēia wahi hahai (ʻekolu mahina ke kaʻawale) i loko o hoʻokahi pule ma mua o ka ʻoki ʻana, hoʻokahi mahina ma hope o ke ʻoki ʻana, a ma ka postoperative adjuvant therapy no ka hoʻāʻo ʻana i ke koko ctDNA.
ʻO ka mea mua, ua ʻike ʻia ua hiki i ka hoʻāʻo ctDNA ke wānana i ka pilikia o ka hoʻi hou ʻana i nā maʻi maʻi maʻi colorectal ma mua, ma mua a ma hope o ka hana. ʻO nā mea maʻi ma mua o ka ctDNA-maikaʻi i ʻoi aku ka kiʻekiʻe o ka hoʻi hou ʻana o ka postoperative ma mua o nā maʻi maʻi ctDNA-negative preoperative (22.0% > 4.7%). ʻO ka hoʻāʻo ʻana o ka ctDNA ma hope o ka hoʻomaka ʻana ua wānana ka hopena hou: hoʻokahi mahina ma hope o ka wehe ʻana o ka radical, ʻo nā maʻi ctDNA-maikaʻi he 17.5 mau manawa e hoʻi hou ma mua o nā maʻi maikaʻi ʻole; Ua ʻike pū ka hui ʻo ka hoʻāʻo ʻana o ctDNA a me CEA i hoʻomaikaʻi iki i ka hana ma ka ʻike ʻana i ka hoʻi hou ʻana (AUC=0.849), akā ʻaʻole nui ka ʻokoʻa i hoʻohālikelike ʻia me ka ctDNA (AUC=0.839) hoʻāʻo wale ʻAʻole nui ka ʻokoʻa i hoʻohālikelike ʻia me ctDNA wale nō (AUC= 0.839).
ʻO ka hoʻonohonoho ʻana i ka maʻi maʻi i hui pū ʻia me nā mea pilikia i kēia manawa ke kumu nui no ka stratification o ka maʻi maʻi maʻi, a i ka paradigm o kēia manawa, he nui ka nui o nā mea maʻi e hoʻi hou [4], a aia kahi koi wikiwiki no nā mea hana stratification maikaʻi e like me ka over-treatment a ma lalo o ka lāʻau lapaʻau e noho pū ana ma ke keʻena. Ma muli o kēia, ua hoʻokaʻawale ka hui i nā poʻe maʻi me ka maʻi kanesa colorectal stage III i loko o nā pūʻulu ʻokoʻa e pili ana i ka loiloi o ka hoʻihoʻi hou ʻana o ke kino (T4/N2) a me ka pilikia haʻahaʻa (T1-3N1)) a me ka manawa mālama adjuvant (3/6 mahina). Ua ʻike ʻia ka hōʻike ʻana he haʻahaʻa haʻahaʻa haʻahaʻa ka hoʻihoʻi ʻana o nā maʻi i loko o ka subgroup kiʻekiʻe o ka ctDNA-positive inā loaʻa iā lākou ʻeono mahina o ka adjuvant therapy; i loko o ka puʻupuʻu haʻahaʻa haʻahaʻa o nā maʻi maʻi ctDNA, ʻaʻohe ʻokoʻa nui ma waena o ka pōʻai hoʻoponopono adjuvant a me nā hopena maʻi; ʻoiai ua loaʻa i ka poʻe maʻi ctDNA-ʻino ka prognosis ʻoi aku ka maikaʻi ma mua o nā maʻi ctDNA-positive a me kahi manawa lōʻihi postoperative recurrence-free period (RFS); 'anuʻu I a me ka maʻi 'aʻai kala II ʻaʻole i loaʻa hou nā maʻi a pau ctDNA-ʻino i loko o ʻelua makahiki; no laila, ʻo ka hoʻohui ʻana o ka ctDNA me nā hiʻohiʻona lapaʻau e manaʻo ʻia e hoʻonui hou i ka stratification pilikia a ʻoi aku ka maikaʻi o ka wānana i ka hoʻi hou ʻana.

Kiʻi 1. Ka nānā ʻana o ka plasma ctDNA ma POM1 no ka ʻike mua ʻana i ka hoʻi hou ʻana o ka maʻi kanesa colorectal.
ʻO nā hopena hou aʻe o ka hoʻāʻo ctDNA ikaika i hōʻike ʻia he ʻoi aku ka kiʻekiʻe o ka pilikia o ka hoʻi hou ʻana i nā poʻe maʻi me ka hoʻāʻo ctDNA maikaʻi ma mua o nā mea maʻi me ka ctDNA maikaʻi ʻole i ka wā o ka nānā ʻana i ka maʻi ma hope o ka hoʻomaʻamaʻa ʻana (ma hope o ka hana radical + adjuvant therapy) (Figure 3ACD), a hiki i ka ctDNA ke hōʻike i ka hoʻi hou ʻana o ka maʻi a hiki i 20 mau mahina ma mua o ke kiʻi kiʻi (Figure 3B), e hāʻawi ana i ka hiki ke ʻike mua i ka maʻi. ka hoʻihoʻi hou ʻana a me ka manawa kūpono.

Kiʻi 2. ka nānā ʻana o ka ctDNA ma muli o ka cohort longitudinal e ʻike i ka hoʻi hou ʻana o ka maʻi maʻi ʻaʻai.

"ʻO ka nui o nā noiʻi lāʻau lapaʻau unuhi i ka maʻi maʻi colorectal e alakaʻi i ka hoʻopaʻi, ʻoi aku ka nui o ka hoʻāʻo ʻana o ka MRD e pili ana i ka ctDNA e hōʻike ana i ka mana nui e hoʻomaikaʻi i ka hoʻokele postoperative o nā maʻi maʻi maʻi colorectal ma o ka hiki ʻana i ka stratification pilikia, ke alakaʻi ʻana i nā hoʻoholo lapaʻau a me ka nānā mua ʻana.

ʻO ka maikaʻi o ke koho ʻana i ka DNA methylation ma ke ʻano he hōʻailona MRD hou ma mua o ka ʻike mutation ʻaʻole ia e koi i ka nānā ʻana i ka genome sequencing holoʻokoʻa o nā ʻiʻo tumo, hoʻohana pololei ʻia no ka hoʻāʻo ʻana i ke koko, a pale i nā hopena maikaʻi ʻole ma muli o ka ʻike ʻana i nā mutations somatic mai ka maʻamau. nā kino, nā maʻi maikaʻi, a me ka hematopoiesis clonal.
Ua hōʻoia kēia haʻawina a me nā noiʻi ʻē aʻe e pili ana i ka hoʻāʻo ʻana i ka MRD e pili ana i ka ctDNA ka mea koʻikoʻi kūʻokoʻa kūʻokoʻa kūʻokoʻa no ka hoʻi hou ʻana o ka pae I-III colorectal cancer a hiki ke hoʻohana ʻia e kōkua i ke alakaʻi ʻana i nā hoʻoholo lapaʻau, me ka "escalation" a me ka "downgrading" o ka adjuvant therapy. ʻO MRD ka mea koʻikoʻi koʻikoʻi kūʻokoʻa kūʻokoʻa no ka hoʻi hou ʻana ma hope o ke kaʻina no ka pae I-III ka maʻi maʻi colorectal.
Ke ulu wikiwiki nei ke kahua o MRD me ka nui o nā mea hou, koʻikoʻi koʻikoʻi a kikoʻī kikoʻī e pili ana i ka epigenetics (DNA methylation and fragmentomics) a me ka genomics (ultra-deep targeted sequencing or whole genome sequencing). Manaʻo mākou e hoʻomau ʻo ColonAiQ® i ka hoʻonohonoho ʻana i nā noiʻi lapaʻau nui a hiki ke lilo i hōʻailona hou o ka hoʻāʻo MRD e hoʻohui i ka hiki, ka hana kiʻekiʻe a me ka hiki ke hoʻohana nui ʻia i ka hana lapaʻau maʻamau.
Nā kuhikuhi
[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. Ka ʻike mua o ka Molecular Residual Disease and Risk Stratification for Stage I to III Colorectal Cancer by Circulating Tumor DNA Methylation. JAMA Oncol. 2023 ʻApelila 20.
[2] "ʻO ke kaumaha o ka maʻi kanesa colorectal i ka heluna kanaka Kina: ua loli anei ia i nā makahiki i hala iho nei? , Ka Nupepa Kina o Epidemiology, Vol. 41, Helu 10, ʻOkakopa 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Kuhi ʻia i ka hanauna e hiki mai ana i ka DNA circulating-tumor DNA no ka nānā ʻana i nā maʻi koena liʻiliʻi i ka maʻi maʻi colonized localized. Ann Oncol. Nov 1, 2019;30(11):1804-1812.
[4] Taieb J, André T, Auclin E. Hoʻomaʻemaʻe i ka adjuvant therapy no ka non-metastatic colon cancer, nā kūlana hou a me nā hiʻohiʻona. Ma'i ma'i 'a'ai Rev. 2019;75:1-11.