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 antcology (idan 33.012) ya buga sakamakon bincike na Jami'ar Shanghai Jiaro da Cancanta na Jami'ar IIP na Cai No Zazzage Tumor DNA Methylation da Haɗarin Haɗari)”. Wannan binciken shine binciken farko na multicenter a cikin duniya don amfani da fasahar PCR na tushen jini na ctDNA multigene methylation don tsinkayar cutar kansa ta launi 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 tsammanin zai inganta haɓakar amfani da asibiti na cutar kansa ta launi mai mahimmanci inganta yanayin rayuwa mai inganci da kulawa da 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 mazaunan mu kuma yana haifar da nauyi na zamantakewa da tattalin arziki. Bisa kididdigar da cibiyar kula da cutar daji ta kasar Sin ta gudanar, an nuna cewa, yawan kudin da ake kashewa a duk shekara a farashin maganin cutar kansar launin fata a kasar Sin ya kai kimanin kashi 6.9 zuwa kashi 9.2 cikin dari, kuma yawan kudin da ake kashewa na lafiyar marasa lafiya a cikin shekara guda na kamuwa da cutar zai iya daukar kashi 60% na kudin shigar 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 don ciwon daji na launin fata 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 tsinkaya da tsinkaya don taimakawa a yanke shawara na jiyya ga marasa lafiya da ke da ciwon hanji mataki na II ko na III. 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 masu fama da cutar kansar launi na II-III (matsayin kusan kashi 70%) sun fi bukatar gaggawar sa ido sosai, sannan girman kasuwan MRD mai kuzarin sa ido kan cutar kansar colorectal ya kai 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 PCR na tushen jini na ctDNA multigene methylation don tsinkayar ciwon daji na launi da kuma sake dawowa tare da hankali, lokaci da kuma farashi mai mahimmanci, 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), babban mujallar kasa da kasa a fagen cututtukan gastrointestinal 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 da kyakkyawan aikin ColonAiQ® ChangAiQ® a farkon gwajin cutar kansa da kuma gano cutar kansa da wuri. 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 a farkon mataki na I-III ciwon daji na launi, ƙungiyar bincike ta haɗa da marasa lafiya 299 tare da mataki na I-III ciwon daji wanda ya yi aikin tiyata mai tsattsauran ra'ayi kuma ya tattara samfurori na jini a kowane mataki na gaba (watanni uku baya) a cikin mako guda bayan tiyata da kuma tiyata, bayan tiyata, bayan wata daya da kuma tiyata. 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 ba shi da mahimmanci idan aka kwatanta da gwajin ctDNA (AUC = 0.839) kadai Bambanci ba shi da mahimmanci idan aka kwatanta da ctDNA kadai (AUC = 0.839).
Shirye-shiryen 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 sake dawowa [4], kuma akwai buƙatar gaggawa don ingantattun kayan aikin stratification kamar yadda yawan jiyya da rashin jiyya suka kasance tare a cikin asibitin. 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
Ci gaba da sakamakon gwajin ctDNA mai tsauri ya nuna cewa haɗarin sake dawowa ya kasance mafi girma a cikin marasa lafiya tare da ingantaccen gwajin ctDNA mai ƙarfi fiye da marasa lafiya da ke da ctDNA mara kyau a lokacin yanayin sake dawowa da cutar bayan ingantaccen magani (bayan tiyata mai tsattsauran ra'ayi + adjuvant far) (Hoto 3ACD), kuma ctDNA na iya nuna yiwuwar sake dawowa da ƙari a farkon farkon watanni 20 (Figure 20). 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 methylation na DNA a matsayin sabon alamar MRD akan gano maye gurbi shine cewa baya buƙatar cikakken jerin jerin kwayoyin halittar ƙwayar cuta, ana amfani dashi kai tsaye don gwajin jini, kuma yana guje wa sakamako mara kyau saboda gano maye gurbin somatic wanda ya samo asali daga kyallen takarda na yau da kullun, cututtuka marasa kyau, da hematopoiesis na clonal.
Wannan binciken da sauran binciken da ke da alaƙa 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 yanke shawara na jiyya, ciki har da "haɓaka" da "ragewa" na adjuvant far MRD shine mafi mahimmancin haɗari mai zaman kanta don sake dawowa bayan tiyata don mataki na I-III ciwon daji na launi.
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. 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?
[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.