Nazari mai yiwuwa binciken: Fasahar ctDNA methylation na tushen PCR yana buɗe sabon zamanin sa ido na MRD don ciwon daji na colorectal

Kwanan nan, JAMA Oncology (IF 33.012) ya buga wani muhimmin sakamakon bincike [1] ta ƙungiyar Farfesa Cai Guo-ring daga Asibitin Ciwon daji na Jami'ar Fudan da Farfesa Wang Jing daga Asibitin Renji na Jami'ar Shanghai Jiao Tong School of Medicine, in Haɗin gwiwa tare da KUNYUAN BIOLOGY: “Gano Farkon Cutar Cutar Kwayar Kwayoyin Halitta da Rarraba Hatsari don Sashe na I zuwa III Ciwon daji Zazzage Tumor DNA Methylation da Haɗarin Haɗari)”. Wannan binciken shine binciken farko na multicenter a cikin duniya don amfani da fasaha na PCR na tushen jini na ctDNA multigene methylation don tsinkayar cutar ciwon daji da kuma sake dawowa, yana samar da mafi kyawun hanyar fasaha da mafita idan aka kwatanta da hanyoyin fasahar gano MRD na yanzu, wanda ake sa ran. don inganta ingantaccen amfani da asibiti na tsinkaya da sake dawowa da cutar kansar launi, da kuma inganta rayuwar marasa lafiya da ingancin rayuwa. Mujallar da editocinta kuma sun tantance binciken sosai, kuma an jera shi a matsayin wata babbar takarda ta shawarwari a wannan fitowar, kuma an gayyaci Farfesa Juan Ruiz-Bañobre daga Spain da Farfesa Ajay Goel daga Amurka don sake duba shi. Har ila yau, GenomeWeb, wata babbar hanyar watsa labaru a Amurka ta ruwaito binciken.

Ciwon daji mai launi (CRC) cuta ce da ta zama ruwan dare gama gari na sashin gastrointestinal a kasar Sin. Alkaluman hukumar bincike kan cutar daji ta IARC na shekarar 2020 sun nuna cewa, sabbin masu kamuwa da cutar sankara 555,000 a kasar Sin sun kai kimanin kashi 1/3 na duniya, yayin da adadin wadanda suka kamu da cutar ya haura zuwa matsayi na biyu na kamuwa da cutar sankara a kasar Sin; Mutuwar 286,000 ta kai kusan kashi 1/3 na duniya, wanda ya zama na biyar mafi yawan sanadin mutuwar cutar kansa a China. Abu na biyar da ya yi sanadiyar mutuwar mutane a China. Abin lura ne cewa a cikin marasa lafiya da aka gano, matakan TNM I, II, III da IV sune 18.6%, 42.5%, 30.7% da 8.2% bi da bi. Fiye da 80% na marasa lafiya suna cikin matsakaici da ƙarshen matakai, kuma 44% daga cikinsu suna da lokaci ɗaya ko heterochronic m metastases zuwa hanta da huhu, wanda ke tasiri sosai ga lokacin rayuwa, yana cutar da lafiyar mazaunanmu kuma yana haifar da matsanancin zamantakewa da tattalin arziki. nauyi. Bisa kididdigar da cibiyar kula da cutar daji ta kasar Sin ta fitar, an ce, yawan kudin da ake kashewa a duk shekara a farashin maganin cutar kansar launin fata a kasar Sin ya kai kusan kashi 6.9 zuwa kashi 9.2 cikin 100, kuma yawan kudaden kiwon lafiyar marasa lafiya a cikin shekara guda na iya daukar nauyin kashi 60 cikin 100 na cutar sankarau. kudin shiga iyali. Masu fama da cutar daji suna fama da cutar kuma suna cikin matsin tattalin arziki mai girma [2].
Kashi 90 cikin 100 na cututtukan daji na launin fata za a iya cire su ta hanyar tiyata, kuma tun da farko an gano ƙwayar cutar, mafi girman adadin rayuwa na shekaru biyar bayan tiyata mai tsattsauran ra'ayi, amma gabaɗayan sake dawowa bayan radical resection har yanzu kusan 30%. Yawan rayuwa na shekaru biyar na cutar kansar launin fata a cikin jama'ar kasar Sin ya kai kashi 90.1%, 72.6%, 53.8% da 10.4% a mataki na I, II, III da IV, bi da bi.
Ƙananan cututtuka (MRD) shine babban abin da ke haifar da sake dawowar ciwace-ciwacen daji bayan jiyya mai mahimmanci. A cikin 'yan shekarun nan, fasahar gano MRD don ciwace-ciwacen ciwace-ciwace ya ci gaba cikin sauri, kuma binciken lura da nauyi da yawa da bincike sun tabbatar da cewa matsayin MRD na baya-bayan nan na iya nuna haɗarin sake dawowa na ciwon daji na colorectal. Gwajin ctDNA yana da fa'idodin kasancewa mara ɓarna, mai sauƙi, mai sauri, tare da babban damar samfurin da kuma shawo kan nau'ikan ƙari.
Ka'idojin NCCN na Amurka game da ciwon daji na hanji da jagororin CSCO na kasar Sin game da ciwon daji na colorectal duka sun bayyana cewa don tabbatar da haɗarin sake dawowa bayan tiyata da zaɓin maganin chemotherapy a cikin ciwon daji na hanji, gwajin ctDNA na iya ba da bayanan tsinkaye da tsinkaya don taimakawa a yanke shawarar jiyya ga marasa lafiya da mataki na II. ko III ciwon daji. Koyaya, yawancin karatun da ake dasu suna mai da hankali kan maye gurbi na ctDNA dangane da fasahar jeri mai girma (NGS), wanda ke da tsari mai rikitarwa, tsawon lokacin jagora, da tsada mai tsada [3], tare da ƙarancin ƙarancin haɓakawa da ƙarancin yaɗuwa tsakanin masu cutar kansa.
A cikin yanayin mataki na III marasa lafiya na launin fata, NGS na tushen ctDNA tsayayyen sa ido yana kashe har $10,000 don ziyara ɗaya kuma yana buƙatar lokacin jira har zuwa makonni biyu. Tare da gwajin multigene methylation a cikin wannan binciken, ColonAiQ®, marasa lafiya na iya samun sa ido na ctDNA mai ƙarfi a kashi goma na farashi kuma su sami rahoto a cikin kwanaki biyu kaɗan.
Dangane da sabbin cututtukan 560,000 na cutar kansar launin fata a kasar Sin a kowace shekara, marasa lafiya na asibiti galibi tare da mataki na II-III ciwon daji (yawan shine kusan 70%) suna da ƙarin buƙatu na gaggawa don sa ido mai ƙarfi, sannan girman kasuwar MRD mai kuzarin sa ido. Ciwon daji na colorectal yana kaiwa miliyoyin mutane kowace shekara.
Ana iya ganin cewa sakamakon binciken yana da muhimmiyar mahimmancin kimiyya da aiki. Ta hanyar manyan binciken bincike na asibiti, ya tabbatar da cewa ana iya amfani da fasaha na tushen PCR na jini na ctDNA multigene methylation don tsinkayar sake dawowa da ciwon daji da kuma sake dawowa tare da hankali, lokaci da ƙimar farashi, mafi kyawun ba da damar madaidaicin magani don amfana da ƙarin masu ciwon daji. . Binciken ya dogara ne akan ColonAiQ®, gwajin methylation mai yawa don ciwon daji na launi wanda KUNY ya haɓaka, wanda ƙimar aikace-aikacen asibiti a farkon farawa da ganewar asali an tabbatar da shi ta hanyar nazarin asibiti na tsakiya.
Gastroenterology (IF33.88), babbar jarida ta kasa da kasa a fannin cututtukan ciki a cikin 2021, ta ba da rahoton sakamakon bincike da yawa na asibitin Zhongshan na Jami'ar Fudan, Asibitin Ciwon daji na Jami'ar Fudan da sauran cibiyoyin kiwon lafiya masu iko tare da KUNYAN Biological, wanda ya tabbatar. kyakkyawan aikin ColonAiQ® ChangAiQ® a farkon tantancewa da farkon gano cutar kansar launin fata, kuma da farko ya bincika Har ila yau yana bincika yuwuwar. aikace-aikace a cikin tsinkayar sa ido na ciwon daji na colorectal.

Don ƙarin tabbatar da aikace-aikacen asibiti na ctDNA methylation a cikin haɗarin haɗari, jagorancin yanke shawara na magani da kuma sa ido kan sake dawowa da wuri a cikin mataki na I-III ciwon daji na launi, ƙungiyar bincike ta haɗa da marasa lafiya 299 tare da ciwon daji na I-III wanda ya yi aikin tiyata mai tsattsauran ra'ayi kuma ya tattara samfuran jini a. kowane maki mai biyo baya (watanni uku baya) a cikin mako guda kafin tiyata, wata daya bayan tiyata, kuma a cikin maganin adjuvant na baya-bayan nan don haɓakar jini gwajin ctDNA.
Na farko, an gano cewa gwajin ctDNA zai iya yin hasashen haɗarin sake dawowa a cikin marasa lafiya na ciwon daji da wuri, duka kafin yin aiki da kuma da wuri. Marasa lafiya na ctDNA da suka riga sun yi aiki suna da yuwuwar sake dawowa bayan tiyata fiye da marasa lafiya marasa lafiya na ctDNA (22.0%> 4.7%). Gwajin ctDNA na farko da aka fara aiki har yanzu yana annabta haɗarin sake dawowa: wata ɗaya bayan tsattsauran ra'ayi, marasa lafiya na ctDNA sun kasance sau 17.5 mafi kusantar sake dawowa fiye da marasa lafiya mara kyau; ƙungiyar ta kuma gano cewa haɗin ctDNA da gwajin CEA sun ɗan inganta aikin a gano sake dawowa (AUC = 0.849), amma bambancin bai kasance mai mahimmanci ba idan aka kwatanta da gwajin ctDNA (AUC = 0.839) kadai Bambanci ba shi da mahimmanci idan aka kwatanta da ctDNA kadai (AUC= 0.839).
Jiyya na asibiti hade da abubuwan haɗari a halin yanzu shine babban tushen haɗarin haɗari na masu cutar kansa, kuma a cikin yanayin da ake ciki yanzu, yawancin marasa lafiya har yanzu suna komawa [4], kuma akwai buƙatar gaggawa don ingantattun kayan aikin daidaitawa azaman magani da yawa Ƙarƙashin magani yana tare a cikin asibiti. Dangane da wannan, ƙungiyar ta rarraba marasa lafiya tare da ciwon daji na launi na III a cikin ƙungiyoyi daban-daban dangane da ƙididdigar haɗarin sake dawowa na asibiti (haɗari mai girma (T4 / N2) da ƙananan haɗari (T1-3N1)) da lokacin jiyya na adjuvant (watanni 3 / 6). Binciken ya gano cewa marasa lafiya a cikin ƙananan ƙananan ƙananan ƙananan marasa lafiya na ctDNA suna da ƙananan sake dawowa idan sun karbi watanni shida na maganin adjuvant; a cikin ƙananan ƙananan ƙananan ƙananan marasa lafiya na ctDNA-tabbatacce, babu wani bambanci mai mahimmanci tsakanin sake zagayowar jiyya da sakamakon haƙuri; yayin da marasa lafiya na ctDNA suna da kyakkyawan hangen nesa fiye da marasa lafiya na ctDNA da kuma tsawon lokacin sake dawowa bayan tiyata (RFS); mataki na I da ƙananan haɗari na II ciwon daji na launi Duk marasa lafiya na ctDNA ba su sake dawowa cikin shekaru biyu ba; sabili da haka, haɗin ctDNA tare da siffofin asibiti ana sa ran zai ƙara inganta haɗarin haɗari da kuma hasashen sake dawowa.

Hoto 1. Binciken ctDNA na Plasma a POM1 don gano farkon cutar ciwon daji
Ƙarin sakamakon sakamakon gwajin ctDNA mai tsauri ya nuna cewa haɗarin sake dawowa ya kasance mafi girma a cikin marasa lafiya tare da gwajin ctDNA mai ƙarfi fiye da marasa lafiya tare da ctDNA mara kyau a lokacin cutar ta sake dawowa yanayin kulawa bayan ingantaccen magani (bayan tiyata na radical + adjuvant therapy) (Hoto 3ACD), kuma ctDNA na iya nuna sake dawowar ƙwayar cuta har zuwa watanni 20 da suka gabata fiye da hoto (Hoto 3B), yana ba da yiwuwar ganowa da wuri. na sake dawowa da cututtuka da sa baki akan lokaci.

Hoto 2. Binciken ctDNA bisa ga ƙungiyar tsayin daka don gano komowar ciwon daji na launi

"Yawancin karatun likitancin fassara a cikin ciwon daji na launi suna jagorantar horo, musamman gwajin MRD na tushen ctDNA yana nuna babban yuwuwar haɓaka kulawar marasa lafiya bayan tiyata ta hanyar ba da damar haɓaka haɗarin sake dawowa, jagorantar yanke shawara na jiyya da sa ido kan sake dawowa da wuri.

Amfanin zabar DNA methylation a matsayin sabon alamar MRD akan gano maye gurbi shine cewa baya buƙatar cikakken jerin jerin kwayoyin halittar ƙwayoyin tumor, ana amfani dashi kai tsaye don gwajin jini, kuma yana guje wa sakamako mai inganci saboda gano maye gurbi wanda ya samo asali daga al'ada. kyallen takarda, m cututtuka, da clonal hematopoiesis.
Wannan binciken da sauran binciken da suka danganci sun tabbatar da cewa gwajin MRD na tushen ctDNA shine mafi mahimmancin haɗari mai zaman kanta don sake dawowa mataki na I-III ciwon daji na launi kuma za'a iya amfani dashi don taimakawa wajen jagorantar shawarwarin jiyya, ciki har da "haɓaka" da "ragewa" na farfadowa na adjuvant. MRD shine mafi mahimmancin haɗari mai zaman kanta don sake dawowa bayan tiyata don mataki na I-III ciwon daji.
Filin MRD yana haɓaka da sauri tare da ƙima mai ƙima, mai mahimmanci da ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun bayanai (DNA methylation and fragmentomics) da genomics (tsarin da aka yi niyya mai zurfi ko cikakken jerin kwayoyin halitta). Muna sa ran cewa ColonAiQ® ya ci gaba da tsara manyan karatun asibiti kuma zai iya zama sabon alamar gwajin MRD wanda ya haɗu da samun dama, babban aiki da araha kuma ana iya amfani da shi sosai a cikin ayyukan asibiti na yau da kullun. "
Magana
[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. Ganewar Farko na Cututtukan Kwayoyin Halitta da Tsarin Haɗari don Sashe na I zuwa III Ciwon Ciwon Ciwon Lala ta hanyar Ciwon Tumor DNA Methylation. JAMA Oncol. Afrilu 20, 2023
[2] "Nauyin ciwon daji na launin fata a cikin jama'ar kasar Sin: ya canza a cikin 'yan shekarun nan? , Jarida ta Sinawa na Epidemiology, Vol. 41, Lamba 10, Oktoba 2020.
[3] Tarazona N, Gimeno-Valiente F, Gambardella V, et al. Matsakaicin jerin tsararraki na gaba na DNA mai yawo-tumor don bin diddigin cututtukan da ba su da yawa a cikin ciwon daji na hanji. Ann Oncol. 1 ga Nuwamba, 2019; 30 (11): 1804-1812.
[4] Taieb J, André T, Auclin E. Refining adjuvant far for non-mestatic colon cancer, sabon matsayi da ra'ayoyi. Maganin Ciwon daji Rev. 2019;75:1-11.