Ọmụmụ ihe ga-eme n'ọdịnihu: teknụzụ ctDNA methylation nke sitere na PCR na-emepe oge ọhụrụ nke onyunyo MRD maka ọrịa cancer colorectal

N'oge na-adịbeghị anya, JAMA Oncology (Ọ BỤRỤ na 33.012) bipụtara ihe nchọpụta dị mkpa [1] site n'aka ndị otu Prof. Cai Guo-ring si Cancer Hospital nke Fudan University na Prof. Wang Jing si Renji Hospital nke Shanghai Jiao Tong University School of Medicine, na mmekorita ya na KUNYUAN BIOLOGY: “Nchọpụta mmalite nke Ọrịa Residual Molecular na Risk Stratification for Stage I to III Colorectal Cancer site na Na-ekesa Tumor DNA Methylation na Stratification Risk)". Ọmụmụ ihe a bụ nke mbụ multicenter ọmụmụ n'ụwa na-etinye PCR dabeere na ọbara ctDNA multigene methylation technology maka colorectal cancer nlọghachite amụma na nlọghachite nlebanya, na-enye ụzọ teknụzụ dị ọnụ ala karịa na ngwọta ma e jiri ya tụnyere ụzọ teknụzụ nchọpụta MRD dị ugbu a, nke a na-atụ anya ya. iji meziwanye ojiji nke amụma nlọghachi ọrịa cancer colorectal na nlekota nke ukwuu, ma mee ka ndụ onye ọrịa dịkwuo mma na ndụ ndụ. A tụlekwara ọmụmụ ihe ahụ nke ukwuu site na akwụkwọ akụkọ na ndị editọ ya, ma depụtakwara ya dị ka akwụkwọ ntụnye isi na mbipụta a, a kpọkwara Prọfesọ Juan Ruiz-Bañobre si Spain na Prọfesọ Ajay Goel si United States ka ha nyochaa ya. GenomeWeb, bụ onye na-ahụ maka mgbasa ozi biomedical na United States kọkwara ọmụmụ ihe a.

Ọrịa cancer colorectal (CRC) bụ ọrịa na-adịghị mma nke tract gastrointestinal na China. 2020 International Agency for Research on Cancer (IARC) data gosiri na 555,000 ọhụrụ ikpe na China ihe dị ka 1/3 nke ụwa, na ọnụ ọgụgụ na-amali elu na nke abụọ ebe nke ọrịa cancer na China; Ọnwụ 286,000 ruru ihe dị ka 1/3 nke ụwa, n'ogo dị ka nke ise kachasị akpata ọnwụ kansa na China. Ihe kpatara ọnwụ nke ise na China. Ọ bụ ihe kwesịrị ịrịba ama na n'ime ndị ọrịa a chọpụtara, usoro TNM I, II, III na IV bụ 18.6%, 42.5%, 30.7% na 8.2% n'otu n'otu. Ihe karịrị 80% nke ndị ọrịa nọ n'etiti na mbubreyo, na 44% n'ime ha nwere metastases n'otu oge ma ọ bụ heterochronic dị anya na imeju na ngụgụ, nke na-emetụta oge ịlanarị, na-etinye ahụike nke ndị bi na anyị n'ihe egwu ma na-akpata nnukwu mmekọrịta mmadụ na ibe ya na akụ na ụba. ibu. Dị ka ọnụ ọgụgụ nke National Cancer Center si kwuo, nkezi mmụba kwa afọ na ọnụ ahịa ọgwụgwọ ọrịa cancer colorectal na China bụ ihe dịka 6.9% ruo 9.2%, na mmefu ahụike onwe onye nke ndị ọrịa n'ime otu afọ nke nyocha nwere ike iburu 60% nke ọrịa ahụ. ego ezinụlọ. Ndị ọrịa kansa na-arịa ọrịa ahụ yana kwa nnukwu nrụgide akụ na ụba [2].
Pasent 90 nke ọnya cancer colorectal nwere ike ịwa ahụ, ma na mbụ achọpụtara etuto ahụ, nke dị elu karịa afọ ise ga-adị ndụ mgbe ịwa ahụ radical resection, ma ọnụ ọgụgụ nlọghachi azụ mgbe radical resection ka dị ihe dịka 30%. Ọnụ ọgụgụ ndụ ndụ afọ ise nke ọrịa cancer colorectal na ndị China bụ 90.1%, 72.6%, 53.8% na 10.4% maka ọkwa I, II, III na IV, n'otu n'otu.
Obere ọrịa fọdụrụnụ (MRD) bụ isi ihe na-ebute nlọghachi azụ etuto ahụ mgbe ọgwụgwọ radical gasịrị. N'ime afọ ndị na-adịbeghị anya, teknụzụ nchọpụta MRD maka etuto siri ike agaala ngwa ngwa, ọtụtụ nyocha nyocha na ntinye aka ekwenyela na ọnọdụ MRD mgbe arụchara ọrụ nwere ike igosi ihe ize ndụ nke ịmaliteghachi ọrịa cancer colorectal mgbe ọ gasịrị. Nnwale ctDNA nwere uru nke ịbụ onye na-adịghị emerụ ahụ, dị mfe, ngwa ngwa, yana ịnweta nlele dị elu yana imeri ụdị dị iche iche nke tumor.
Ntuziaka NCCN US maka ọrịa cancer eriri afọ na ntuziaka CSCO nke China maka ọrịa cancer colorectal abụọ na-ekwukwa na maka mkpebi ihe ize ndụ nlọghachi azụ azụ na nhọrọ chemotherapy adjuvant na ọrịa cancer colon, ule ctDNA nwere ike ịnye ozi amụma na amụma iji nyere aka na mkpebi ọgwụgwọ adjuvant maka ndị ọrịa nwere ọkwa II. ma ọ bụ III ọrịa cancer colon. Otú ọ dị, ọtụtụ ọmụmụ ihe dị ugbu a na-elekwasị anya na mmụgharị ctDNA dabere na nkà na ụzụ na-emepụta ihe dị elu (NGS), nke nwere usoro mgbagwoju anya, ogologo oge na-eri, na ọnụ ahịa dị elu [3], na-enwe ntakịrị ụkọ nke izugbe na ọnụ ala dị ala n'etiti ndị ọrịa cancer.
N'ihe banyere ndị ọrịa cancer colorectal III, ctDNA dabeere na NGS na-akwụ ụgwọ ihe ruru $10,000 maka otu nleta na-achọ oge nchere ihe ruru izu abụọ. Site na ule multigene methylation n'ime ọmụmụ ihe a, ColonAiQ®, ndị ọrịa nwere ike ịnwe nlekota ctDNA siri ike na otu ụzọ n'ụzọ iri nke ọnụ ahịa wee nweta akụkọ n'ime ihe dị ka ụbọchị abụọ.
Dị ka 560,000 ọhụrụ ọrịa cancer colorectal na China kwa afọ, ndị ọrịa na-adakarị na ọkwa II-III colorectal cancer (ọnụ ọgụgụ dị ihe dị ka 70%) nwere mkpa ngwa ngwa maka nleba anya siri ike, yabụ nha ahịa nke MRD nleba anya siri ike nke cancer colorectal na-eru ọtụtụ nde mmadụ kwa afọ.
Enwere ike ịhụ na nsonaazụ nyocha nwere mkpa sayensị dị mkpa na nke bara uru. Site n'ọmụmụ ihe ọmụmụ ụlọ ọgwụ buru ibu, ọ kwadoro na enwere ike iji teknụzụ PCR dabeere na ctDNA multigene methylation maka amụma nlọghachi ọrịa cancer nke colorectal na nleba anya nlọghachi azụ na ma uche, oge na ọnụ ahịa dị irè, na-eme ka ọgwụ ziri ezi na-erite uru karịa ndị ọrịa cancer. . Ọmụmụ ihe a dabere na ColonAiQ®, ule methylation multi-gene methylation maka ọrịa cancer colorectal nke KUNY mepụtara, onye uru ngwa ụlọ ọgwụ ya na nyocha mmalite na nchoputa ka akwadoro site na nyocha ụlọ ọgwụ etiti.
Gastroenterology (IF33.88), akwụkwọ akụkọ mba ụwa kachasị elu na ngalaba nke ọrịa eriri afọ na 2021, kọrọ nsonaazụ nyocha multicenter nke Hospitallọ Ọgwụ Zhongshan nke Mahadum Fudan, Hospitallọ Ọgwụ Cancer nke Mahadum Fudan na ụlọ ọrụ ahụike ndị ọzọ nwere ikike na njikọ KUNYAN Biological, nke gosipụtara. arụmọrụ kachasị mma nke ColonAiQ® ChangAiQ® na nyocha mmalite na nchọpụta mmalite nke ọrịa cancer colorectal, wee nyochaa ya na mbụ Ọ na-enyochakwa ike ya. ngwa na nlekota prognosis nke cancer colorectal.

Iji kwadokwuo ngwa ụlọ ọgwụ nke ctDNA methylation n'ime ihe ize ndụ, na-eduzi mkpebi ọgwụgwọ na nleba anya nlọghachi azụ n'oge I-III colorectal cancer, ndị otu nyocha ahụ gụnyere ndị ọrịa 299 nwere ọrịa cancer I-III colorectal bụ ndị a na-awa ahụ na-anakọta ihe nlele ọbara na ihe nleba anya nke ọ bụla (ọnwa atọ dị iche) n'ime otu izu tupu ịwa ahụ, otu ọnwa mgbe a wachara ya ahụ, yana na ọgwụgwọ adjuvant mgbe arụchara ọrụ maka ọbara dị ike. Nyocha ctDNA.
Nke mbu, achoputara na nnwale ctDNA nwere ike ibu amụma ihe ize ndụ nke nlọghachi na ndị ọrịa cancer colorectal n'oge, ma tupu ịwa ahụ ma n'oge emechaa. Ndị ọrịa nwere ctDNA tupu ịwa ahụ nwere ohere dị elu nke nlọghachi azụ azụ karịa ndị ọrịa ctDNA na-adịghị mma (22.0%> 4.7%). Nnwale ctDNA na-aga n'ihu n'oge ka na-ebu amụma ihe ize ndụ nlọghachi azụ: otu ọnwa ka radical resection gasịrị, ndị ọrịa ctDNA dị mma nwere ugboro 17.5 nwere ike ịmaliteghachi karịa ndị ọrịa na-adịghị mma; Ndị otu ahụ chọpụtakwara na ctDNA na CEA jikọtara ọnụ na-anwale obere arụmọrụ dị mma n'ịchọpụta nlọghachi azụ (AUC=0.849), mana ọdịiche ahụ abaghị uru ma e jiri ya tụnyere ctDNA (AUC = 0.839) ule naanị Ọdịiche adịchaghị ma e jiri ya tụnyere ctDNA naanị (AUC= 0,839).
Nhazi ụlọ ọgwụ jikọtara ya na ihe ndị dị ize ndụ bụ isi ihe ndabere maka ịkpachapụ anya nke ndị ọrịa cancer n'ihe ize ndụ, na n'ọnọdụ dị ugbu a, ọnụ ọgụgụ dị ukwuu nke ndị ọrịa ka na-alọghachi [4], na ọ dị mkpa ngwa ngwa maka ngwá ọrụ stratification ka mma dị ka ọgwụgwọ na ọgwụgwọ. n'okpuru ọgwụgwọ na-ebikọ ọnụ na ụlọ ọgwụ. Dabere na nke a, ndị otu ahụ kewara ndị ọrịa nwere ọrịa cancer agba nke III n'ime obere ngalaba dị iche iche dabere na nyocha ihe egwu nlọghachi nke ụlọ ọgwụ (ihe egwu dị elu (T4 / N2) na obere ihe egwu (T1-3N1)) na oge ọgwụgwọ adjuvant (ọnwa 3/6). Nnyocha ahụ chọpụtara na ndị ọrịa nọ n'òtù ndị nwere nnukwu ihe ize ndụ nke ndị na-arịa ọrịa ctDNA nwere obere nlọghachi azụ ma ọ bụrụ na ha nwetara ọnwa isii nke ọgwụgwọ adjuvant; na obere obere ihe ize ndụ nke ndị ọrịa ctDNA dị mma, ọ dịghị nnukwu ọdịiche dị n'etiti usoro ọgwụgwọ adjuvant na nsonaazụ onye ọrịa; ebe ndị ọrịa ctDNA na-adịghị mma nwere prognosis ka mma karịa ndị ọrịa nwere ctDNA na ogologo oge nlọghachị n'efu (RFS); ogbo I na obere ihe ize ndụ ogbo II cancer colorectal Ndị ọrịa niile na-adịghị mma ctDNA enweghị nlọghachite n'ime afọ abụọ; ya mere, a na-atụ anya ijikọ ctDNA na njirimara ụlọọgwụ ga-eme ka ihe ize ndụ dịkwuo elu ma buo amụma nlọghachi nke ọma.

Ọnụọgụ 1. Nyocha ctDNA Plasma na POM1 maka nchọpụta mmalite nke nlọghachi ọrịa cancer colorectal
Nsonaazụ ọzọ nke nyocha ctDNA dị ike gosipụtara na ihe ize ndụ nke nlọghachi dị elu nke ukwuu na ndị ọrịa nwere nnwale ctDNA dị mma karịa ndị ọrịa nwere ctDNA na-adịghị mma n'oge usoro nleba anya nlọghachi nke ọrịa mgbe ọgwụgwọ doro anya (mgbe ịwa ahụ radical + adjuvant therapy) (Nyocha 3ACD), na ctDNA ahụ nwere ike igosi nlọghachi azụ azụ ruo ọnwa 20 tupu ịse foto (Njirimara 3B), na-enye ohere nke nchọpụta mbụ. nke nlọghachi ọrịa na ntinye aka n'oge.

Ọgụgụ 2. Nyocha ctDNA dabere na ndị otu ogologo ogologo iji chọpụta nlọghachi ọrịa cancer colorectal

"Ọnụ ọgụgụ dị ukwuu nke ọmụmụ ọgwụ ntụgharị asụsụ na ọrịa cancer colorectal na-eduga ọzụzụ ahụ, karịsịa nyocha MRD dabeere na ctDNA na-egosi ikike dị ukwuu iji welie nlekọta ahụike nke ndị ọrịa cancer colorectal site n'ịkwalite ihe ize ndụ nlọghachi azụ, na-eduzi mkpebi ọgwụgwọ na nleba anya nlọghachi azụ n'oge.

Uru nke ịhọrọ DNA methylation dị ka ihe nrịbama MRD ọhụrụ karịa nchọpụta mmụgharị bụ na ọ chọghị nyocha usoro genome zuru oke nke anụ ahụ tumor, a na-eji ya eme nnwale ọbara, ma na-ezere nsonaazụ ụgha n'ihi nchọpụta nke mmụgharị somatic sitere na nkịtị. anụ ahụ, ọrịa na-adịghị mma, na clonal hematopoiesis.
Ọmụmụ ihe a na ọmụmụ ihe ndị ọzọ metụtara ya na-akwado na nyocha MRD dabeere na ctDNA bụ ihe kachasị mkpa dị ize ndụ nke onwe maka nlọghachite nke ọrịa cancer colorectal I-III na enwere ike iji nyere aka na-eduzi mkpebi ọgwụgwọ, gụnyere "ịbawanye" na "downgrading" nke ọgwụgwọ adjuvant. MRD bụ ihe kacha mkpa nwere onwe ya n'ihe ize ndụ maka nlọghachi azụ mgbe a wachara ya ahụ maka ogbo I-III colorectal cancer.
Ugbo nke MRD na-etolite ngwa ngwa site na otutu nyocha ohuru, nke siri ike na nke a kapịrị ọnụ dabere na epigenetics (DNA methylation and fragmentomics) na genomics (usoro ezubere iche nke miri emi ma ọ bụ usoro genome dum). Anyị na-atụ anya na ColonAiQ® na-aga n'ihu na-ahazi ihe ọmụmụ ụlọ ọgwụ buru ibu ma nwee ike bụrụ ihe ngosi ọhụrụ nke ule MRD na-ejikọta ohere, ịrụ ọrụ dị elu na oke ego ma nwee ike iji ya mee ihe na usoro ọgwụgwọ oge niile."
Ntụaka
[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. Nchọpụta mmalite Ọrịa Mgbochi Molecular na Stratification Risk for Stage I to III Colorectal Cancer site na-ekesa Tumor DNA Methylation. JAMA Oncol. Eprel 20, 2023.
[2] " Ibu nke ọrịa cancer colorectal na ndị China: ọ gbanwere n'afọ ndị na-adịbeghị anya? , Akwụkwọ akụkọ China nke Epidemiology, Vol. 41, Nọmba 10, Ọktoba 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Ezubere iche usoro nke ọgbọ na-esote nke DNA na-ekesa tumor maka nsuso obere ọrịa fọdụrụnụ na ọrịa kansa eriri afọ. Ann Oncol. Nọvemba 1, 2019; 30 (11): 1804-1812 .
[4] Taieb J, André T, Auclin E. Nnụcha ọgwụgwọ adjuvant maka ọrịa cancer akwara na-abụghị metastatic, ụkpụrụ ọhụrụ na echiche. Ọgwụgwọ Ọrịa Cancer Mkpu 2019;75:1-11 .