Kubudirira kweanotarisira kudzidza: PCR-yakavakirwa ropa ctDNA methylation tekinoroji inovhura nguva nyowani yeMRD yekutarisa cancer colorectal.

Munguva ichangopfuura, JAMA Oncology (IF 33.012) yakabudisa tsvakurudzo yakakosha yekutsvakurudza [1] neboka raProf. Cai Guo-ring kubva kuCancer Hospital yeFudan University uye Prof. Wang Jing kubva kuRenji Hospital yeShanghai Jiao Tong University School of Medicine, pamwe chete neKUNYUAN BIOLOGY: "Kutanga Kuonekwa kweMolecular Residual Residual neCancer Cancer Kutenderera Tumor DNA Methylation uye Risk Stratification) ”. Chidzidzo ichi ndicho chekutanga chidzidzo chepasi rose chekushandisa PCR-based blood ctDNA multigene methylation tekinoroji yekufembera kwegomarara rekare uye kuongorora kudzokorora, ichipa nzira inodhura yehunyanzvi uye mhinduro kana ichienzaniswa nevepo MRD yekuona tekinoroji nzira, inotarisirwa kuvandudza zvakanyanya kushandiswa kwekiriniki kwegomarara reruvara rwekare uye kutarisisa hupenyu hwemurwere. Chidzidzo ichi chakaongororwawo zvakanyanya nejenari nevapepeti varo, uye chakanyorwa sebepa rekurudziro rakakosha munyaya iyi, uye Muzvinafundo Juan Ruiz-Bañobre vekuSpain naMuzvinafundo Ajay Goel vekuUnited States vakakokwa kuzoongorora. Chidzidzo ichi chakataurwa zvakare neGenomeWeb, inotungamira biomedical media muUnited States.

Colourectal cancer (CRC) imota yakashata yakajairika yemudumbu muChina. 2020 International Agency for Research on Cancer (IARC) data inoratidza kuti 555,000 nyaya nyowani muChina dzinenge 1/3 yepasirese, nehuwandu hwechiitiko ichisvetukira kunzvimbo yechipiri yekenza dzakajairika muChina; 286,000 nzufu dzinenge chikamu chimwe chete/ 3 chepasirese, chiri pachishanu chinowanzokonzera kufa kwegomarara muChina. Chikonzero chechishanu chekufa muChina. Zvinokosha kuziva kuti pakati pevarwere vakabatwa nechirwere ichi, nhanho dzeTNM I, II, III neIV i18.6%, 42.5%, 30.7% ne8.2% zvichiteerana. Vanopfuura 80% yevarwere vari pakati nepakati uye yekupedzisira nhanho, uye 44% yavo ine panguva imwe chete kana heterochronic kure metastases kuchiropa nemapapu, izvo zvinokanganisa zvakanyanya nguva yekupona, zvinokanganisa hutano hwevagari vedu uye zvinokonzeresa kuremerwa kwemagariro nehupfumi. Zvinoenderana nenhamba dzeNational Cancer Center, avhareji yekuwedzera pagore mumutengo wekurapa cancer muChina ingangoita 6.9% kusvika 9.2%, uye mashandisirwo ehutano hwevarwere mukati megore rimwe rekuongororwa anogona kutora 60% yemari yemhuri. Varwere vegomarara vari kurwara nechirwere ichi uye zvakare vari pasi pekumanikidzwa kukuru kwehupfumi [2].
Zvikamu makumi mapfumbamwe kubva muzana zvemaronda egomarara remukati anogona kubviswa nekuvhiyiwa, uye kukurumidza kuoneka bundu, kukwira kwemakore mashanu ekupona mushure mekuvhiyiwa kwakadzama, asi mwero wekudzokazve mushure mekuvhiyiwa kwakadzama kuchiri kunosvika makumi matatu muzana. Makore mashanu ekupona kwegomarara re colorectal muhuwandu hweChinese i90.1%, 72.6%, 53.8% uye 10.4% yematanho I, II, III uye IV, zvichiteerana.
Minimal residual disease (MRD) ndicho chikonzero chikuru chekudzoka kwebundu mushure mekurapwa kwakanyanya. Mumakore achangopfuura, tekinoroji yekuona MRD yemamota akasimba yakakwira nekukurumidza, uye zvidzidzo zvakati wandei zvekutarisa uye zvekupindira zvakasimbisa kuti postoperative MRD mamiriro anogona kuratidza njodzi yekudzokororwa kwepashure kwegomarara re colorectal. ctDNA yekuongorora ine zvakanakira kusave isingapindiki, iri nyore, nekukurumidza, ine yakakwirira sampuli kuwanikwa uye kukunda bundu heterogeneity.
Nhungamiro dzeUS NCCN dzegomarara remukoloni uye nhungamiro yeChinese CSCO yegomarara remukati zvese zvinoti kune mushure mekuvhiyiwa kudzokororwa kwenjodzi yekutemerwa uye adjuvant chemotherapy kusarudzwa mucolon cancer, kuongororwa kwectDNA kunogona kupa ruzivo rwekufungidzira uye rwekufanotaura kubatsira mukugadzirisa adjuvant kurapa kwevarwere vane nhanho II kana III colon cancer. Zvisinei, zvidzidzo zvakawanda zviripo zvinotarisa ctDNA mutations yakavakirwa pahupamhi hwepamusoro-soro sequencing tekinoroji (NGS), iyo ine hurongwa hwakaoma, nguva yakareba yekutungamira, uye kudhura kwakanyanya [3], nekushaikwa kushoma kwe generalizability uye kuderera kwehuwandu pakati pevarwere vegomarara.
Panyaya yevarwere vegomarara repadanho rechitatu, NGS-based ctDNA dynamic monitoring inodhura kusvika kumadhora zviuru gumi pakushanya kamwe chete uye inoda nguva yekumirira inosvika mavhiki maviri. Iine multigene methylation bvunzo muchidzidzo ichi, ColonAiQ®, varwere vanogona kuve neane simba ctDNA yekutarisisa pachikamu chegumi chemutengo uye kuwana chirevo mukati memazuva maviri mashoma.
Zvinoenderana ne560,000 nyaya nyowani dzegomarara remukati muChina gore rega rega, varwere vekiriniki kunyanya vane nhanho II-III colorectal cancer (iyo chikamu chingangoita makumi manomwe muzana) vane kudiwa kwekukurumidzira kwekutariswa kwakasimba, ipapo saizi yemusika yeMRD yekutarisisa kwechirwere checolorectal inosvika mamirioni avanhu gore rega rega.
Zvinogona kuonekwa kuti tsvakurudzo yemigumisiro ine zvakakosha zvesayenzi uye zvinoshanda zvakakosha. Kuburikidza nezvidzidzo zvakakura zvinotarisirwa zvekiriniki, zvakasimbisa kuti PCR-based blood ctDNA multigene methylation tekinoroji inogona kushandiswa kufanotaura kenza yecolorectal kudzokorora uye kudzokororwa kwekutarisa nekunzwa, kuenderana nenguva uye mutengo-kushanda, zviri nani kugonesa chaiyo mushonga kubatsira varwere vekenza. Chidzidzo ichi chakavakirwa paColonAiQ®, bvunzo dzakawanda-gene methylation yegomarara remukati rakagadzirwa neKUNY, iyo ine kukosha kwekushandisa kwekiriniki mukutanga kuongororwa uye kuongororwa kwakasimbiswa nepakati chekiriniki kudzidza.
Gastroenterology (IF33.88), iyo yepamusoro-soro bepanhau repasi rose mumunda wezvirwere zvemudumbu muna 2021, yakashuma mhedzisiro yekutsvagisa yakawanda yeZhongshan Hospital yeFudan University, Cancer Hospital yeFudan University uye mamwe masangano ezvehutano ane chiremera akabatana neKUNYAN Biological, iyo yakasimbisa kushanda kwakanaka kweColonAiQ® ChangAiQ ® ChangAiQ ® kuvhenekwa uye kuongororwa kwekutanga kwegomarara. zvakare inoongorora iyo inogona kushandiswa mukufungidzira kwekutarisa cancer colorectal.

Kuenderera mberi kusimbisa kushandiswa kwekiriniki kwectDNA methylation munjodzi stratification, kutungamira sarudzo dzekurapa uye kukurumidza kudzokorora kutarisisa muchikamu I-III colorectal cancer, timu yekutsvagisa yaisanganisira varwere ve299 vane stage I-III colorectal cancer vakavhiyiwa zvakanyanya uye vakaunganidza masampula eropa pane yega yega yekutevera (mwedzi mitatu yakaparadzana, mushure memwedzi mumwe mushure mekuvhiyiwa kwakaparadzaniswa) mukati memwedzi mumwe mushure mekuvhiyiwa dynamic blood ctDNA test.
Chekutanga, zvakaonekwa kuti kuongororwa kwectDNA kwaigona kufanotaura njodzi yekudzokororwa muvarwere vegomarara rekare kare, zvese zvisati zvaitika uye nekutanga mushure mekuvhiya. Preoperative ctDNA-positive varwere vaive nemukana wepamusoro wekudzoka kwepashure kupfuura preoperative ctDNA-negative varwere (22.0%> 4.7%). Early postoperative ctDNA yekuongorora ichiri kufanotaura njodzi yekudzokazve: mwedzi mumwe mushure mekugadziriswa kwakanyanya, ctDNA-positive varwere vaiva 17.5 nguva dzakawanda dzekudzoka kune varwere vasina kunaka; boka racho rakaonawo kuti ctDNA yakasanganiswa uye CEA kuedza kwakavandudza zvishoma kushanda pakuona kudzokorora (AUC = 0.849), asi mutsauko wakanga usina kukosha kana uchienzaniswa neCTDNA (AUC = 0.839) kuongororwa chete Musiyano wakanga usina kukosha kana uchienzaniswa nectDNA chete (AUC = 0.839).
Chirwere chekiriniki chakasanganiswa nezvinhu zvine njodzi pari zvino ndicho chikonzero chikuru chekuisa njodzi yevarwere vekenza, uye mune yazvino paradigm, nhamba huru yevarwere ichiri kudzoka [4], uye pane kudiwa kwekukurumidzira kwezvishandiso zviri nani zvekugadzirisa sezvo kurapa kwakanyanya uye kushomeka kwekurapa kunogara mukiriniki. Zvichienderana neizvi, timu yakaisa varwere vane nhanho III colorectal cancer muzvikamu zvakasiyana zvichienderana nekiriniki yekudzokorora njodzi yekuongorora (njodzi huru (T4 / N2) uye yakaderera njodzi (T1-3N1)) uye adjuvant kurapwa nguva (3/6 mwedzi). Kuongorora kwakawana kuti varwere vari muchikamu chepamusoro-chepamusoro chevarwere vane ctDNA-positive vaiva nehuwandu hwekudzoka zvakare kana vakagamuchira mwedzi mitanhatu yeadjuvant therapy; mune yakaderera-ngozi subgroup ctDNA-positive varwere, pakanga pasina musiyano mukuru pakati adjuvant kurapwa cycle uye murwere migumisiro; nepo ctDNA-negative varwere vane fungidziro iri nani kupfuura ctDNA-positive varwere uye yakareba postoperative recurrence-free period (RFS); danho I uye yakaderera-ngozi danho II colorectal cancer Vese ctDNA-negative varwere vakanga vasina kudzokorora mukati memakore maviri; saka, kubatanidzwa kwectDNA nemaitiro ekiriniki inotarisirwa kuwedzera kuwedzera njodzi stratification uye zvirinani kufanotaura kudzokorora.

Mufananidzo 1. Kuongororwa kwePlasma ctDNA paPOM1 yekukurumidza kutariswa kwegomarara remukati rekudzoka.
Mimwe mibairo yesimba rekuongorora ctDNA yakaratidza kuti njodzi yekudzoka yakakwira zvakanyanya kune varwere vane yakanaka dynamic ctDNA yekuongorora pane kune varwere vane negative ctDNA panguva yechirwere chekudzokorora chekutarisa chikamu mushure mekurapa kwakasimba (mushure mekuvhiyiwa kwakanyanya + adjuvant therapy) (Mufananidzo 3ACD), uye kuti ctDNA inogona kuratidza kuti bundu rinogona kudzoka kusvika kumwedzi 20 yekufungidzira kudzokorora uye kupindira panguva.

Mufananidzo 2. ctDNA kuongororwa kwakavakirwa pane longitudinal cohort kuona colorectal cancer kudzoka.

"Chiverengero chikuru chezvidzidzo zvemushonga wekushandura mune colorectal cancer inotungamira chirango, kunyanya ctDNA-yakavakirwa MRD bvunzo inoratidza mukana mukuru wekusimudzira postoperative manejimendi evarwere vegomarara remukati nekugonesa kudzokororwa kwenjodzi, kutungamira sarudzo dzekurapa uye nekutanga kudzoka kwekutarisa.

Mukana wekusarudza DNA methylation senovel MRD marker pamusoro pekutaridzirwa kwekuchinja ndeyekuti haidi genome yese sequencing kuongororwa kwe tumor tissues, inoshandiswa zvakananga kuongororwa ropa, uye inodzivirira nhema-yakanaka mhedzisiro nekuda kwekuonekwa kwe somatic shanduko inobva kune yakajairwa matishu, benign zvirwere, uye clonal hematopoiesis.
Ichi chidzidzo uye zvimwe zvidzidzo zvine hukama zvinosimbisa kuti ctDNA-yakavakirwa MRD bvunzo ndiyo inonyanya kukosha yakazvimirira njodzi yekudzoka kwedanho I-III cancer cancer uye inogona kushandiswa kubatsira kutungamira sarudzo dzekurapa, kusanganisira "kukwira" uye "kudzikira" kweadjuvant therapy MRD ndiyo inonyanya kukosha yakazvimiririra njodzi yekudzoka mushure mekuvhiyiwa kwedanho I-III colorectal cancer.
Munda weMRD uri kukurumidza kushanduka nehuwandu hwehutsva, hunyoro uye hutsananguro hwekuongorora hunobva pa epigenetics (DNA methylation uye fragmentomics) uye genomics (ultra-deep targeted sequencing kana yose genome sequencing). Tinotarisira kuti ColonAiQ® inoramba ichironga zvidzidzo zvekiriniki zvakakura uye inogona kuve chiratidzo chitsva cheMRD bvunzo inosanganisa kuwanikwa, kuita kwepamusoro uye kugona uye inogona kushandiswa zvakanyanya mumuitiro wekiriniki.
References
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