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

Munguva pfupi yapfuura, JAMA Oncology (IF 33.012) yakaburitsa tsvakiridzo yakakosha [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, mu kubatana neKUNYUAN BIOLOGY: "Kuonekwa Kwekutanga KweMolecular Residual Disease uye Risk Stratification yeStage I kusvika III Colorectal Cancer kuburikidza Kutenderera Tumor DNA Methylation uye Risk Stratification) ”. Chidzidzo ichi ndicho chekutanga chidzidzo chepasi rose chekushandisa PCR-based blood ctDNA multigene methylation tekinoroji yekufembera kenza ye colorectal kudzokorora uye kuongorora kudzokorora, ichipa nzira inodhura yehunyanzvi nzira uye mhinduro kana ichienzaniswa neiripo MRD yekuona tekinoroji nzira, inotarisirwa. kuvandudza zvakanyanya kushandiswa kwekiriniki kwekufanotaura kwegomarara re colorectal uye kutarisa, uye nekuvandudza zvakanyanya kupona kwemurwere uye hupenyu hwehupenyu. 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, zvinoisa mungozi hutano hwevagari vedu uye kukonzera kurema kwemagariro nehupfumi. mutoro. 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% yevarwere. mari 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.
Iyo US NCCN nhungamiro yegomarara remukoloni uye nhungamiro yeChinese CSCO yegomarara remukati zvese zvinoti kune mushure mekuvhiyiwa kudzokorora njodzi yekutemerwa uye adjuvant chemotherapy kusarudzwa mucolon cancer, ctDNA yekuongorora inogona kupa prognostic uye kufanotaura ruzivo kubatsira mukugadzirisa adjuvant kurapwa 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 vanonyanya vane nhanho II-III colorectal cancer (iyo chikamu chingangoita makumi manomwe muzana) vane kudiwa kwekukurumidzira kwekutariswa kwakasimba, kozoti saizi yemusika yeMRD yekutarisa ine simba. colorectal cancer inosvika mamirioni avanhu gore rega rega.
Zvinogona kuonekwa kuti tsvakurudzo yemigumisiro ine zvakakosha zvesayenzi uye zvinoshanda zvakakosha. Kuburikidza nezvidzidzo zvekiriniki zvakakura, zvakasimbisa kuti PCR-based blood ctDNA multigene methylation tekinoroji inogona kushandiswa kufembera kenza yecolorectal uye kuongorora kudzokorora nekunzwa, kuenderana nenguva uye mutengo-kushanda, zviri nani kuita kuti mushonga chaiwo ubatsire 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 nemamwe masangano ekurapa ane chiremera akabatana neKUNYAN Biological, iyo yakasimbisa. kuita kwakanakisa kweColonAiQ® ChangAiQ® mukutanga kuongororwa uye nekutanga kuongororwa kwegomarara remukati, uye pakutanga akaongorora Iyo zvakare inoongorora iyo inogona kushandiswa mukufungidzira kwekutarisa cancer colorectal.

Kuenderera mberi nekusimbisa kushandiswa kwekiriniki kwectDNA methylation munjodzi stratification, kutungamira sarudzo dzekurapa uye nekutanga kudzokorora kutarisisa muchikamu I-III colorectal cancer, timu yekutsvagurudza yaisanganisira varwere mazana maviri nemakumi mapfumbamwe nevapfumbamwe vane nhanho I-III cancer cancer vakavhiyiwa zvakanyanya uye vakaunganidza masampuli eropa pa. imwe neimwe yekutevera (mwedzi mitatu yakaparadzana) mukati mevhiki imwe isati yavhiyiwa, mwedzi mumwe mushure mekuvhiyiwa, uye mune postoperative adjuvant therapy 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 yakasanganiswa ctDNA uye CEA yekuongorora yakavandudza zvishoma pakuona kudzokorora (AUC = 0.849), asi mutsauko wakanga usina kukosha kana uchienzaniswa nectDNA (AUC = 0.839) yekuongorora 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 vachiri kudzoka [4], uye pane kudikanwa kwekukurumidzira kwezvishandiso zviri nani zvekugadzirisa sekurapa zvakanyanya uye. kusarapwa 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 mhedzisiro yesimba rekuongorora ctDNA yakaratidza kuti njodzi yekudzokorora yakakwira zvakanyanya kune varwere vane yakanaka dynamic ctDNA yekuongorora pane varwere vane negative ctDNA panguva yechirwere chekudzokazve chekutarisa chikamu mushure mekurapa kwakasimba (mushure mekuvhiyiwa kwakanyanya + adjuvant therapy) (Mufananidzo 3ACD), uye kuti ctDNA inogona kuratidza bundu kudzoka kusvika kumwedzi makumi maviri pamberi pekufungidzira (Mufananidzo 3B), ichipa mukana wekukurumidza kuonekwa kwechirwere. 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 pekutsvaga shanduko ndeyekuti haidi genome yese sequencing yekuongorora tumor tissues, inoshandiswa zvakananga kuongororwa ropa, uye inodzivirira nhema-zvakanaka mhedzisiro nekuda kwekuonekwa kwe somatic shanduko inobva kune yakajairwa. Zvirwere, zvirwere zvinotapukira, uye clonal hematopoiesis.
Ichi chidzidzo uye zvimwe zvidzidzo zvine hukama zvinosimbisa kuti ctDNA-based MRD bvunzo ndiyo inonyanya kukosha yakazvimiririra njodzi yekudzoka kwedanho I-III cancer cancer uye inogona kushandiswa kubatsira kutungamira sarudzo dzekurapa, kusanganisira "kukwira" uye "kudzikisira" kweadjuvant therapy. MRD ndiyo inonyanya kukosha yakazvimiririra njodzi yekudzokazve mushure mekuvhiyiwa kwechikamu 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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