Hoʻomaka ka haʻawina holomua: ʻO ka ʻenehana methylation ctDNA koko PCR e wehe i kahi au hou o ka nānā ʻana o MRD no ka maʻi kanesa colorectal

I kēia mau lā aku nei, ua paʻi ʻo JAMA Oncology (IF 33.012) i kahi hopena noiʻi koʻikoʻi [1] e ka hui o Prof. Cai Guo-ring mai ka Halemai Kanesa o ke Kulanui ʻo Fudan a me Prof. Wang Jing mai ka Halemai Renji o ke Kula Lapaʻau ʻo Shanghai Jiao Tong University, me ka laulima ʻana me KUNYUAN BIOLOGY: "ʻIke mua ʻana i ka maʻi Molecular Residual a me ka Stratification Risk no ka Stage I a III Colorectal Cancer ma o Circulating Tumor DNA Methylation a me Risk Stratification)". ʻO kēia haʻawina ka haʻawina multicenter mua ma ka honua e hoʻopili i ka ʻenehana methylation multigene ctDNA koko PCR no ka wānana hou ʻana o ke kanesa colorectal a me ka nānā ʻana i ka recurrence, e hāʻawi ana i kahi ala loea a me ka hopena ʻoi aku ka maikaʻi o ke kumukūʻai i hoʻohālikelike ʻia me nā ʻano ʻenehana ʻike MRD e kū nei, kahi i manaʻo ʻia e hoʻomaikaʻi nui i ka hoʻohana lapaʻau o ka wānana a me ka nānā ʻana i ka recurrence cancer colorectal, a hoʻomaikaʻi nui i ke ola o ka mea maʻi a me ke ʻano o ke ola. Ua loiloi nui ʻia ke aʻo ʻana e ka puke pai a me kāna mau mea hoʻoponopono, a ua helu ʻia ʻo ia he pepa ʻōlelo paipai koʻikoʻi ma kēia puke, a ua kono ʻia ʻo Polofesa Juan Ruiz-Bañobre mai Sepania a me Polofesa Ajay Goel mai ʻAmelika Hui Pū ʻIa e loiloi iā ia. Ua hōʻike pū ʻia ke aʻo ʻana e GenomeWeb, kahi pāpāho biomedical alakaʻi ma ʻAmelika Hui Pū ʻIa.

ʻO ke kanesa Colorectal (CRC) kahi puʻupuʻu ʻino maʻamau o ke ala gastrointestinal ma Kina. Hōʻike ka ʻikepili o ka International Agency for Research on Cancer (IARC) 2020 he 555,000 mau hihia hou ma Kina no kahi 1/3 o ka honua, me ka lele ʻana o ka helu hanana i ka lua o ka wahi o nā kanesa maʻamau ma Kina; 286,000 mau make no kahi 1/3 o ka honua, ʻo ia ke kumu ʻelima o ka make ʻana o ke kanesa ma Kina. ʻO ke kumu ʻelima o ka make ma Kina. He mea kūpono ia i waena o nā 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% pakahi. ʻOi aku ma mua o 80% o nā maʻi ma nā pae waena a me nā pae hope, a he 44% o lākou he metastases mamao like a heterochronic paha i ke akepaʻa a me ka māmā, kahi e hoʻopilikia nui ai i ka wā ola, hoʻoweliweli i ke olakino o ko mākou poʻe noho a hoʻoulu i ke kaumaha pilikanaka a me ka hoʻokele waiwai. Wahi a nā helu helu o ke Kikowaena Kanesa Lahui, ʻo ka piʻi ʻana o ke kumukūʻai o ka mālama ʻana i ka maʻi kanesa colorectal ma Kina ma kahi o 6.9% a 9.2% i kēlā me kēia makahiki, a ʻo ka lilo ʻana o ke olakino pilikino o nā maʻi i loko o hoʻokahi makahiki o ka hōʻoia ʻana hiki ke lawe i 60% o ka loaʻa kālā o ka ʻohana. Ke ʻeha nei nā maʻi kanesa i ka maʻi a ma lalo hoʻi o ke kaomi waiwai nui [2].
Hiki ke wehe ʻia he kanaiwakūmāiwa pakeneka o nā ʻeha o ke kanesa colorectal ma ke ʻoki ʻana, a ʻo ka ʻike mua ʻia ʻana o ka puʻupuʻu, ʻoi aku ke kiʻekiʻe o ka helu ola ʻelima makahiki ma hope o ka ʻoki ʻoki radical, akā ʻo ka helu hoʻi hou ma hope o ka ʻoki radical he 30% nō naʻe. ʻO nā helu ola ʻelima makahiki o ke kanesa colorectal i ka heluna kanaka Kina he 90.1%, 72.6%, 53.8% a me 10.4% no nā pae I, II, III a me IV, kēlā me kēia.
ʻO ka maʻi koena liʻiliʻi (MRD) kekahi kumu nui o ka hoʻi hou ʻana o ka puʻupuʻu ma hope o ka mālama radical. I nā makahiki i hala iho nei, ua holomua wikiwiki ka ʻenehana ʻike MRD no nā puʻupuʻu paʻa, a ua hōʻoia kekahi mau haʻawina nānā a me nā hana komo kaumaha e hiki i ke kūlana MRD postoperative ke hōʻike i ka pilikia o ka hoʻi hou ʻana o ke kanesa colorectal postoperative. Loaʻa i ka hoʻāʻo ctDNA nā pono o ka noninvasive, maʻalahi, wikiwiki, me ka hiki ke kiʻekiʻe o ka laʻana a me ka lanakila ʻana i ka heterogeneity tumor.
ʻO nā alakaʻi a ka US NCCN no ka maʻi ʻaʻai kolona a me nā alakaʻi a ka CSCO Kina no ka maʻi ʻaʻai colorectal e ʻōlelo nei no ka hoʻoholo ʻana i ka pilikia recurrence postoperative a me ke koho ʻana i ka chemotherapy adjuvant i ka maʻi ʻaʻai kolona, ​​hiki i ka hoʻāʻo ctDNA ke hāʻawi i ka ʻike prognostic a me ka wānana e kōkua i nā hoʻoholo lapaʻau adjuvant no nā poʻe maʻi me ke kanesa kolona pae II a i ʻole III. Eia nō naʻe, ʻo ka hapa nui o nā haʻawina e kū nei e kālele ana i nā mutations ctDNA e pili ana i ka ʻenehana sequencing high-throughput (NGS), nona kahi kaʻina hana paʻakikī, ka manawa alakaʻi lōʻihi, a me ke kumukūʻai kiʻekiʻe [3], me ka nele iki o ka generalizability a me ka haʻahaʻa haʻahaʻa i waena o nā poʻe maʻi kanesa.
I ke ʻano o nā maʻi maʻi ʻaʻai colorectal pae III, ʻo ke kumukūʻai o ka nānā ʻana i ka ctDNA dynamic NGS a hiki i $10,000 no hoʻokahi kipa ʻana a koi ʻia kahi manawa kali a hiki i ʻelua pule. Me ka hoʻāʻo methylation multigene i loko o kēia haʻawina, ʻo ColonAiQ®, hiki i nā maʻi ke loaʻa ka nānā ʻana i ka ctDNA dynamic ma ka hapaʻumi o ke kumukūʻai a loaʻa kahi hōʻike i loko o ʻelua lā wale nō.
Wahi a nā hihia hou he 560,000 o ke kanesa colorectal ma Kina i kēlā me kēia makahiki, ʻo nā mea maʻi lapaʻau me ke kanesa colorectal pae II-III (ʻo ka hapa ma kahi o 70%) he koi nui no ka nānā ʻana i ka dynamic, a laila ʻo ka nui o ka mākeke o ka nānā ʻana i ka dynamic MRD o ke kanesa colorectal e hiki aku i nā miliona o ka poʻe i kēlā me kēia makahiki.
Hiki ke ʻike ʻia he koʻikoʻi koʻikoʻi ka ʻepekema a me ka hana o nā hopena noiʻi. Ma o nā haʻawina lapaʻau nui e hiki mai ana, ua hōʻoia ʻia e hiki ke hoʻohana ʻia ka ʻenehana methylation multigene ctDNA koko PCR no ka wānana ʻana i ka hoʻi hou ʻana o ke kanesa colorectal a me ka nānā ʻana i ka hoʻi hou ʻana me ka ʻike, ka manawa kūpono a me ke kumukūʻai kūpono, e hiki ai i ka lāʻau lapaʻau pololei ke pōmaikaʻi i nā poʻe maʻi kanesa. Hoʻokumu ʻia ke aʻo ʻana ma ColonAiQ®, kahi hoʻāʻo methylation multi-gene no ke kanesa colorectal i hoʻomohala ʻia e KUNY, nona ka waiwai noi lapaʻau i ka nānā mua ʻana a me ka ʻike ʻana ua hōʻoia ʻia e kahi haʻawina lapaʻau waena.
Ua hōʻike ʻo Gastroenterology (IF33.88), ka puke pai honua kiʻekiʻe loa ma ke kahua o nā maʻi gastrointestinal i ka makahiki 2021, i nā hopena noiʻi multicenter o ka Halemai ʻo Zhongshan o ke Kulanui ʻo Fudan, ka Halemai Kanesa o ke Kulanui ʻo Fudan a me nā ʻoihana lapaʻau mana ʻē aʻe me KUNYAN Biological, nāna i hōʻoia i ka hana maikaʻi loa o ColonAiQ® ChangAiQ® i ka nānā mua ʻana a me ka ʻike mua ʻana i ka maʻi ʻaʻai colorectal, a ua ʻimi mua ʻia ka ʻimi ʻana i ka hiki ke hoʻohana ʻia i ka nānā ʻana i ka prognosis o ka maʻi ʻaʻai colorectal.

No ka hōʻoia hou ʻana i ka hoʻopili lapaʻau o ka ctDNA methylation i ka hoʻokaʻawale ʻana i ka pilikia, ke alakaʻi ʻana i nā hoʻoholo lapaʻau a me ka nānā mua ʻana i ka hoʻi hou ʻana i ka maʻi kanesa colorectal pae I-III, ua hoʻokomo pū ka hui noiʻi i 299 mau maʻi me ka maʻi kanesa colorectal pae I-III i hana ʻia i ke ʻoki radical a hōʻiliʻili i nā hāpana koko ma kēlā me kēia wahi hahai (ʻekolu mahina ke kaʻawale) i loko o hoʻokahi pule ma mua o ke ʻoki ʻana, hoʻokahi mahina ma hope o ke ʻoki ʻana, a ma ka lāʻau lapaʻau adjuvant postoperative no ka hoʻāʻo ʻana i ka ctDNA koko dynamic.
ʻO ka mea mua, ua ʻike ʻia hiki i ka hoʻāʻo ʻana o ka ctDNA ke wānana i ka pilikia o ka hoʻi hou ʻana i nā maʻi kanesa colorectal i ka wā mua, ma mua o ke ʻoki ʻana a me ka wā mua ma hope o ke ʻoki ʻana. ʻOi aku ka kiʻekiʻe o ka hiki i nā maʻi ctDNA-positive ma mua o ke ʻoki ʻana i ka manawa ma mua o ke ʻoki ʻana ma mua o ke ʻoki ʻana (22.0% > 4.7%). Ua wānana mau ka hoʻāʻo ʻana o ka ctDNA postoperative mua i ka pilikia o ka hoʻi hou ʻana: hoʻokahi mahina ma hope o ka radical resection, ʻoi aku ka nui o ka poʻe maʻi ctDNA-positive i ka hoʻi hou ʻana ma mua o nā maʻi maikaʻi ʻole; ua ʻike pū ka hui ua hoʻomaikaʻi iki ka hui pū ʻana o ka hoʻāʻo ctDNA a me CEA i ka hana i ka ʻike ʻana i ka hoʻi hou ʻana (AUC=0.849), akā ʻaʻole koʻikoʻi ka ʻokoʻa i hoʻohālikelike ʻia me ka hoʻāʻo ctDNA (AUC=0.839) wale nō ʻAʻole koʻikoʻi ka ʻokoʻa i hoʻohālikelike ʻia me ka ctDNA wale nō (AUC=0.839).
ʻO ke kahua lapaʻau i hui pū ʻia me nā mea pilikia ke kumu nui no ka hoʻokaʻawale ʻana i nā pilikia o nā maʻi kanesa, a ma ke ʻano o kēia manawa, nui ka poʻe maʻi e hoʻi hou mai ana [4], a aia kahi pono wikiwiki no nā mea hana stratification maikaʻi aʻe e like me ka mālama nui ʻana a me ka mālama ʻole ʻia e noho pū ana ma ke keʻena lapaʻau. Ma muli o kēia, ua hoʻokaʻawale ka hui i nā maʻi me ke kanesa colorectal pae III i nā hui like ʻole e pili ana i ka loiloi pilikia recurrence lapaʻau (pilikia kiʻekiʻe (T4/N2) a me ka pilikia haʻahaʻa (T1-3N1)) a me ka manawa mālama adjuvant (3/6 mahina). Ua ʻike ka loiloi he haʻahaʻa ka nui o ka recurrence o nā maʻi ma ka hui kiʻekiʻe o nā maʻi ctDNA-positive inā loaʻa iā lākou ʻeono mahina o ka adjuvant therapy; ma ka hui haʻahaʻa o nā maʻi ctDNA-positive, ʻaʻohe ʻokoʻa koʻikoʻi ma waena o ke kaʻina hana adjuvant a me nā hopena o ka maʻi; ʻoiai ʻoi aku ka maikaʻi o ka prognosis o nā maʻi ctDNA-negative ma mua o nā maʻi ctDNA-positive a me kahi manawa postoperative recurrence-free (RFS); ʻo ke kahua I a me ka maʻi kanesa colorectal pae II haʻahaʻa ʻAʻohe recurrence o nā maʻi ctDNA-negative i loko o ʻelua mau makahiki; no laila, ʻo ka hoʻohui ʻana o ctDNA me nā hiʻohiʻona lapaʻau e manaʻo ʻia e hoʻonui hou aku i ka hoʻokaʻawale ʻana o ka pilikia a wānana maikaʻi 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 ke kanesa colorectal
Ua hōʻike ʻia nā hopena hou aʻe o ka hoʻāʻo ʻana o ka ctDNA ikaika ua ʻoi aku ka kiʻekiʻe o ka pilikia o ka hoʻi hou ʻana i nā poʻe maʻi me ka hoʻāʻo ctDNA ikaika maikaʻi ma mua o nā poʻe maʻi me ka ctDNA maikaʻi ʻole i ka wā o ka nānā ʻana i ka hoʻi hou ʻana o ka maʻi ma hope o ka mālama hope loa (ma hope o ke ʻoki radical + adjuvant therapy) (Kiʻi 3ACD), a hiki i ka ctDNA ke hōʻike i ka hoʻi hou ʻana o ka puʻupuʻu a hiki i 20 mau mahina ma mua o ke kiʻi ʻana (Kiʻi 3B), e hāʻawi ana i ka hiki ke ʻike mua i ka hoʻi hou ʻana o ka maʻi a me ka hana kūpono.

Kiʻi 2. ka loiloi ctDNA e pili ana i ka cohort longitudinal e ʻike i ka hoʻi hou ʻana o ke kanesa colorectal

"He nui nā haʻawina lapaʻau unuhi i ke kanesa colorectal e alakaʻi i ke aʻo ʻana, ʻoiai ka hoʻāʻo ʻana o ka MRD e pili ana i ka ctDNA e hōʻike ana i ka hiki ke hoʻomaikaʻi i ka hoʻokele postoperative o nā maʻi kanesa colorectal ma o ka hiki ʻana i ka stratification pilikia recurrence, ke alakaʻi ʻana i nā hoʻoholo lapaʻau a me ka nānā ʻana i ka recurrence mua."

ʻO ka pōmaikaʻi o ke koho ʻana i ka DNA methylation ma ke ʻano he māka MRD hou ma mua o ka ʻike ʻana i ka mutation, ʻaʻole ia e koi i ka nānā ʻana o ka genome holoʻokoʻa o nā ʻiʻo tumor, hoʻohana pololei ʻia no ka hoʻāʻo ʻana i ke koko, a pale i nā hopena wahaheʻe ma muli o ka ʻike ʻana i nā mutations somatic e puka mai ana mai nā ʻiʻo maʻamau, nā maʻi benign, a me ka hematopoiesis clonal.
Ua hōʻoia kēia haʻawina a me nā haʻawina pili ʻē aʻe ʻo ka hoʻāʻo ʻana o ka MRD e pili ana i ka ctDNA ka mea pilikia kūʻokoʻa koʻikoʻi loa no ka hoʻi hou ʻana o ka maʻi ʻaʻai colorectal pae I-III 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 pilikia kūʻokoʻa koʻikoʻi loa no ka hoʻi hou ʻana ma hope o ke ʻoki ʻana no ka maʻi ʻaʻai colorectal pae I-III.
Ke loli koke nei ke kahua o MRD me ka nui o nā hoʻāʻo hou, koʻikoʻi a kikoʻī hoʻi e pili ana i ka epigenetics (DNA methylation a me fragmentomics) a me genomics (ultra-deep targeted sequencing a i ʻole ka holoʻokoʻa genome sequencing). Manaʻo mākou e hoʻomau ʻo ColonAiQ® i ka hoʻonohonoho ʻana i nā haʻawina lapaʻau nui a hiki ke lilo i hōʻailona hou o ka hoʻāʻo MRD e hoʻohui i ka hiki ke komo, ka hana kiʻekiʻe a me ke kumukūʻai kūpono a 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. ʻIke mua ʻia o ka maʻi koena Molecular a me ka Stratification Risk no ka Stage I a i III Colorectal Cancer ma o ka Circulating Tumor DNA Methylation. JAMA Oncol. 2023 ʻApelila 20.
[2] “Ke kaumaha o ka maʻi kanesa colorectal i ka heluna kanaka Kina: ua loli anei ia i nā makahiki i hala iho nei? , Chinese Journal of Epidemiology, Vol. 41, No. 10, ʻOkakopa 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Hoʻolālā ʻia ka hoʻonohonoho ʻana o ka hanauna hou o ka DNA tumor circulating no ka hahai ʻana i nā maʻi koena liʻiliʻi i loko o ka maʻi ʻaʻai colon kūloko. Ann Oncol. Nov 1, 2019;30(11):1804-1812.
[4] Taieb J, André T, Auclin E. Ke hoʻomaʻemaʻe nei i ka lāʻau lapaʻau adjuvant no ka maʻi ʻaʻai kolona non-metastatic, nā kūlana hou a me nā manaʻo. Cancer Treat Rev. 2019;75:1-11.