Chidzidzo chitsva: Tekinoroji yePCR-based blood ctDNA methylation inovhura nguva itsva yekutarisa MRD yekenza ye colorectal

Munguva pfupi yapfuura, JAMA Oncology (IF 33.012) yakaburitsa mhedzisiro yakakosha yekutsvagisa [1] nechikwata chaProf. Cai Guo-ring vekuCancer Hospital yeFudan University naProf. Wang Jing vekuRenji Hospital yeShanghai Jiao Tong University School of Medicine, vachibatsirana neKUNYUAN BIOLOGY: "Kuonekwa Kwechirwere Chemamorekuru Nekupatsanurwa Kwengozi Kwechikamu Chekutanga kusvika Chechitatu Chekenza yeColorectal kuburikidza neCirculating Tumor DNA Methylation uye Risk Stratification)". Chidzidzo ichi ndicho chekutanga kudzidza kwakawanda pasi rose kushandisa tekinoroji yePCR-based blood ctDNA multigene methylation yekufanotaura kudzoka kwekenza yeColorectal uye kutarisa kudzoka kwayo, ichipa nzira yehunyanzvi uye mhinduro inodhura zvishoma kana tichienzanisa nenzira dziripo dzeMRD detection, iyo inotarisirwa kuvandudza zvakanyanya kushandiswa kwekiriniki kwekufanotaura kudzoka kwekenza yeColorectal uye kutarisa, uye kuvandudza zvakanyanya kurarama kwemurwere uye hupenyu hwake. Chidzidzo ichi chakaongororwawo zvakanyanya nemagazini nevapepeti vayo, uye chakanyorwa sepepa guru rekurudziro muchinyorwa chino, uye Purofesa Juan Ruiz-Bañobre wekuSpain naPurofesa Ajay Goel wekuUnited States vakakokwa kuti vaongorore. Chidzidzo ichi chakataurwawo neGenomeWeb, iyo inotungamira munhau dzezvekurapa muUnited States.

Gomarara remudumbu (CRC) igomarara rinowanzoitika mudumbu muChina. Data reInternational Agency for Research on Cancer (IARC) ra2020 rinoratidza kuti nyaya itsva 555,000 muChina dzinosvika chikamu chimwe muzvitatu chenyika, nehuwandu hwezvirwere zvichikwira kusvika panzvimbo yechipiri yekenza dzakajairika muChina; kufa kwevanhu 286,000 kunodarika chikamu chimwe muzvitatu chenyika, zvichionekwa sechikonzero chechishanu chinowanzo kukonzera kufa kwevanhu vane kenza muChina. Chikonzero chechishanu cherufu muChina. Zvakakosha kuziva kuti pakati pevarwere vakaonekwa, nhanho dzeTNM I, II, III neIV dziri 18.6%, 42.5%, 30.7% uye 8.2% zvichiteerana. Vanopfuura 80% yevarwere vari pakati nepakati nepakupedzisira, uye 44% yavo vane chirwere ichi panguva imwe chete kana kuti chenguva pfupi chichienda kuchiropa nemapapu, izvo zvinokanganisa zvakanyanya nguva yekurarama, zvinoisa hutano hwevagari vedu panjodzi uye zvinokonzera mutoro wakakura munharaunda nehupfumi. Zvichienderana nehuwandu hweNational Cancer Center, avhareji yekuwedzera kwegore negore kwemari yekurapa gomarara remudumbu muChina inenge iri pakati pe6.9% kusvika 9.2%, uye mari inoshandiswa pakurapa varwere mukati megore rimwe chete rekuongororwa inogona kutora 60% yemari yemhuri. Varwere vegomarara vari kutambura nechirwere ichi uye vari pasi pekumanikidzwa kukuru kwehupfumi [2].
Makumi mapfumbamwe muzana emaronda egomarara remudumbu anogona kubviswa nekuvhiyiwa, uye bundu rikaonekwa nekukurumidza, huwandu hwekurarama kwemakore mashanu mushure mekuvhiyiwa kwakakura, asi huwandu hwekudzokazve mushure mekuvhiyiwa kwakakura huchiri kusvika pa30%. Huwandu hwekurarama kwemakore mashanu egomarara remudumbu muvanhu vekuChina huri 90.1%, 72.6%, 53.8% uye 10.4% yematanho I, II, III neIV, zvichiteerana.
Zvirwere zvidiki zvinosara (MRD) ndicho chikonzero chikuru chekudzokororwa kwegomarara mushure mekurapwa zvakanyanya. Mumakore achangopfuura, tekinoroji yekuona MRD yemagomarara akaoma yafambira mberi nekukurumidza, uye zvidzidzo zvakawanda zvekuongorora uye zvepakati zvakasimbisa kuti mamiriro eMRD mushure mekuvhiyiwa anogona kuratidza njodzi yekudzoka kwegomarara remudumbu mushure mekuvhiyiwa. Kuongororwa kweCTDNA kune zvakanakira zvekuti hazvipindi, zviri nyore, zvinokurumidza, uye zvinowanikwa nyore nyore uye zvinokunda kusiyana kwegomarara.
Nhungamiro dzeUS NCCN dzekenza yemudumbu uye nhungamiro dzeChinese CSCO dzekenza yemudumbu dzinoti pakuongorora njodzi yekudzoka mushure mekuvhiyiwa uye kusarudzwa kwemishonga inobatsira mukenza yemudumbu, kuongororwa kwectDNA kunogona kupa ruzivo rwekufanotaura uye ruzivo rwekufanotaura kuti rubatsire mukusarudza kurapwa kwe adjuvant kune varwere vane kenza yemudumbu yedanho rechipiri kana rechitatu. Zvisinei, zvidzidzo zvakawanda zviripo zvinotarisa pakuchinja kwectDNA zvichibva pa high-throughput sequencing technology (NGS), iyo ine maitiro akaomarara, nguva yakareba, uye inodhura zvakanyanya [3], nekushaikwa kwekupararira kwechirwere uye kupararira kwakaderera pakati pevarwere vekenza.
Kana vari varwere vane gomarara remudumbu rechikamu chechitatu, NGS-based ctDNA dynamic monitoring inodhura kusvika ku$10,000 pakushanya kamwe chete uye inoda nguva yekumirira inosvika mavhiki maviri. Nekuyedzwa kwe multigene methylation muchidzidzo chino, ColonAiQ®, varwere vanogona kuongororwa kwe ctDNA dynamic nechikamu chimwe chete chemutengo uye kuwana mushumo mumazuva maviri chete.
Zvichienderana nezviitiko zvitsva 560,000 zvegomarara remudumbu muChina gore rega rega, varwere vazhinji vane gomarara remudumbu rechikamu chechipiri kusvika chechitatu (chikamu chacho chingangoita 70%) vane kudiwa kukuru kwekuongororwa kwakasimba, asi kukura kwemusika kweMRD dynamic monitoring yegomarara remudumbu rechikamu chinosvika mamiriyoni evanhu gore rega rega.
Zvinogona kuonekwa kuti mhedzisiro yekutsvagisa ine kukosha kwakakosha kwesainzi uye kwekushanda. Kuburikidza nezvidzidzo zvikuru zvekiriniki, zvakasimbisa kuti tekinoroji yePCR-based blood ctDNA multigene methylation inogona kushandiswa pakufanotaura kudzoka kwekenza yemudumbu uye kutarisa kudzoka kwayo nekunzwisisa, nenguva uye nekushandisa mari, zvichiita kuti mushonga wakarurama ubatsirwe varwere vakawanda vekenza. Chidzidzo ichi chakavakirwa paColonAiQ®, bvunzo yemethylation yemajini akawanda yakagadzirwa neKUNY, iyo kukosha kwayo mukuongorora kwekutanga uye kuongororwa kwakasimbiswa neongororo yekiriniki.
Gastroenterology (IF33.88), iyo magazini yepamusoro yepasi rose munyaya dzezvirwere zvemudumbu muna 2021, yakashuma mhedzisiro yekutsvagisa kwakawanda kweZhongshan Hospital yeFudan University, Cancer Hospital yeFudan University nedzimwe nzvimbo dzekurapa dzine mukurumbira pamwe chete neKUNYAN Biological, iyo yakasimbisa kushanda kwakanaka kweColonAiQ® ChangAiQ® mukuongorora kwekutanga uye kuongororwa kwekutanga kwekenza yemudumbu, uye pakutanga yakaongorora kushandiswa kwayo mukutarisa kenza yemudumbu.

Kuti vawedzere kusimbisa kushandiswa kwe ctDNA methylation mukurapa kwenjodzi, vachitungamira sarudzo dzekurapa uye kutarisa kudzoka kwekutanga kwekenza yemudumbu yechikamu I-III, timu yekutsvagisa yaisanganisira varwere 299 vane kenza yemudumbu yechikamu I-III vakavhiyiwa zvakanyanya uye vakatora sampuro dzeropa panzvimbo imwe neimwe yekutevera (mwedzi mitatu yakasiyana) mukati mevhiki imwe vasati vavhiyiwa, mwedzi mumwe mushure mekuvhiyiwa, uye mukurapa kwe adjuvant mushure mekuvhiyiwa kwe dynamic blood ctDNA testing.
Chekutanga, zvakaonekwa kuti kuongororwa kwe ctDNA kunogona kufanotaura njodzi yekudzoka kwechirwere muvarwere vane kenza yemudumbu kare, vese vasati vavhiyiwa uye vasati vavhiyiwa. Varwere vane ctDNA vasati vavhiyiwa vaive nemukana wakakura wekudzoka kwechirwere mushure mekuvhiyiwa kupfuura varwere vasina ctDNA vasati vavhiyiwa (22.0% > 4.7%). Kuongororwa kwe ctDNA mushure mekuvhiyiwa kwakafanotaura njodzi yekudzoka kwechirwere: mwedzi mumwe mushure mekuvhiyiwa zvakanyanya, varwere vane ctDNA vaive nemukana wekudzokazve ka17.5 kupfuura varwere vasina; chikwata chakawanawo kuti kuongororwa kwe ctDNA neCEA kwakabatana kwakavandudza mashandiro ekuona kudzoka kwechirwere (AUC=0.849), asi mutsauko wacho wakanga usina kukosha kana tichienzanisa nekuongororwa kwe ctDNA (AUC=0.839) chete. Musiyano wacho wakanga usina kukosha kana tichienzanisa ne ctDNA chete (AUC=0.839).
Kuongororwa kwekiriniki pamwe chete nezvinhu zvine njodzi pari zvino ndiyo hwaro hukuru hwekupatsanurwa kwenjodzi dzevarwere vegomarara, uye mumaonero aripo, varwere vakawanda vachiri kudzoka [4], uye pane kudiwa kukuru kwezvishandiso zviri nani zvekupatsanurwa sezvo kurapwa kwakanyanya uye kusarapwa zvakanaka kuripo mukiriniki. Zvichibva pane izvi, timu yakaisa varwere vane chirwere chegomarara remudumbu muzvikamu zvakasiyana zvichienderana nekuongorora njodzi yekudzokera kwechirwere (njodzi huru (T4/ N2) uye njodzi shoma (T1-3N1)) uye nguva yekurapwa kweadjuvant (mwedzi 3/6). Ongororo iyi yakawana kuti varwere vari muboka revarwere vane ctDNA-positive vane njodzi huru vaive nehuwandu hwakaderera hwekudzokera kwechirwere kana vakagamuchira kurapwa kweadjuvant kwemwedzi mitanhatu; muboka revarwere vane ctDNA-positive vane njodzi shoma, pakanga pasina musiyano mukuru pakati pechirongwa chekurapa kweadjuvant nemigumisiro yevarwere; nepo varwere vane ctDNA-negative vaive nefungidziro iri nani kupfuura varwere vane ctDNA-positive uye nguva refu isina kudzoka kwechirwere mushure mekuvhiyiwa (RFS); Danho rekutanga nedanho rechipiri rekenza yemudumbu ine njodzi shoma. Varwere vese vasina ctDNA havana kudzoka mukati memakore maviri; saka, kubatanidzwa kwectDNA nezvinhu zvekurapa kunotarisirwa kuwedzera kupatsanurwa kwenjodzi uye kufanotaura zviri nani kudzoka kwechirwere.

Mufananidzo 1. Kuongororwa kwePlasma ctDNA paPOM1 kuti uone nekukurumidza kudzoka kwekenza ye colorectal
Mimwe mhedzisiro yekuongororwa kwe dynamic ctDNA yakaratidza kuti njodzi yekudzokororwa kwechirwere yaive yakakwira zvakanyanya muvarwere vane positive dynamic ctDNA testing pane varwere vane negative ctDNA panguva yekutarisa kudzoka kwechirwere mushure mekurapwa kwakasimba (mushure mekuvhiyiwa kwakanyanya + adjuvant therapy) (Mufananidzo 3ACD), uye kuti ctDNA inogona kuratidza kudzoka kwegomarara kusvika kumwedzi makumi maviri isati yasvika pakufungidzira (Mufananidzo 3B), zvichipa mukana wekuona kudzoka kwechirwere nekukurumidza uye kupindira panguva yakakodzera.

Mufananidzo 2. Ongororo yectDNA yakavakirwa pa longitudinal cohort kuti ione kudzoka kwekenza ye colorectal

"Huwandu hwakawanda hwezvidzidzo zvekurapa kwekurapa kenza yemudumbu hwakaita sehunhu huri kutungamira muchikoro ichi, kunyanya kuongororwa kweMRD kwakavakirwa pactDNA kunoratidza mukana mukuru wekuvandudza kurapwa kwevarwere vekenza yemudumbu mushure mekuvhiyiwa nekugonesa kupatsanurwa kwenjodzi yekudzokazve kwechirwere, kutungamira sarudzo dzekurapa uye kutarisa kudzokazve kwechirwere nekukurumidza."

Chinhu chakanaka pakusarudza DNA methylation sechiratidzo chitsva cheMRD pane kuona shanduko ndechekuti haidi kuongororwa kwese kwegenome sequencing kwematishu egomarara, inoshandiswa zvakananga kuongororwa ropa, uye inodzivirira mhedzisiro yenhema nekuda kwekuona shanduko dzemuviri dzinobva mumatishu akajairwa, zvirwere zvisina njodzi, uye clonal hematopoiesis.
Chidzidzo ichi pamwe nezvimwe zvidzidzo zvine chekuita nazvo zvinosimbisa kuti kuongororwa kweMRD kwakavakirwa pactDNA ndiyo inonyanya kukosha panjodzi yekudzoka kwekenza yemudumbu yechikamu chekutanga kusvika chechitatu uye inogona kushandiswa kubatsira kutungamira sarudzo dzekurapa, kusanganisira "kuwedzera" uye "kudzikiswa" kwekurapa kweadjuvant. MRD ndiyo inonyanya kukosha panjodzi yekudzoka kwekenza yemudumbu yechikamu chekutanga kusvika chechitatu mushure mekuvhiyiwa.
Basa reMRD riri kukurumidza kuchinja nekuongorora kwakawanda, kwakanyatsojeka uye kwakanangana kwakavakirwa pa epigenetics (DNA methylation uye fragmentomics) uye genomics (ultra-deep targeted sequencing kana whole genome sequencing). Tinotarisira kuti ColonAiQ® icharamba ichironga zvidzidzo zvekiriniki zvakakura uye inogona kuva chiratidzo chitsva chekuyedzwa kweMRD kunosanganisa kuwanikwa, kushanda kwepamusoro uye kugona kutenga uye kunogona kushandiswa zvakanyanya mukurapa kwakajairika.
Mareferensi
[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. Kuonekwa Kwechirwere Chemamorekuru Nekupatsanurwa Kwengozi Yechirwere Chekenza Yemudumbu Chekutanga Kubva Padanho Rekutanga kusvika Rechitatu Nekushandisa Methylation yeDNA Rectum. JAMA Oncol. 2023 Kubvumbi 20.
[2] "Mutoro wechirwere chegomarara remudumbu muvanhu vekuChina: chakachinja here mumakore achangopfuura? , Chinese Journal of Epidemiology, Vol. 41, Nhamba 10, Gumiguru 2020."
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, nevamwe. Vakaronga kutevedzana kweDNA regomarara rinotenderera muchizvarwa chinotevera kuti vatevedzere chirwere chidiki chakasara mukenza yemudumbu. Ann Oncol. Mbudzi 1, 2019;30(11):1804-1812.
[4] Taieb J, André T, Auclin E. Kugadzirisa kurapa kwekubatsira kwekenza yemudumbu isina kupararira, mitemo mitsva nemaonero. Cancer Treat Rev. 2019;75:1-11.