MINI BINCIKE
Madogarar yaƙi da ciwon daji: alamomin cutar kansa kawai
Chengchen Qian1, Xiaolong Zou2, Wei Li1,3, Yinshan Li4, Wenqiang Yu5
1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, Sin;2 Sashen Nazarin Gabaɗaya, Asibitin Haɗin Kan Farko na Jami'ar Kiwon Lafiya ta Harbin, Harbin 150001, China;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, China;4 Asibitin Jama'a na Ningxia Hui mai cin gashin kansa, Jami'ar Kiwon Lafiya ta Ningxia, Yinchuan 750002, Sin;5 Cibiyar Kiwon Lafiyar Jama'a ta Shanghai & Sashen Nazarin Gabaɗaya, Asibitin Huashan & Ciwon daji Metastasis Institute & Laboratory of RNA Epigenetics, Cibiyoyin Kimiyyar Halittu, Kwalejin Kiwon Lafiya ta Shanghai, Jami'ar Fudan, Shanghai 200032, China
GASKIYA
Ciwon daji shine kan gaba wajen mutuwa a duniya.Gano kansa da wuri zai iya rage yawan mace-mace na kowane nau'in ciwon daji;duk da haka, ingantattun masu gano ƙwayoyin cuta da wuri ba su da ƙarancin nau'ikan cututtukan daji.DNA methylation koyaushe ya kasance babban makasudin sha'awa saboda DNA methylation yawanci yana faruwa kafin wasu canje-canjen kwayoyin halitta.Yayin da ake bincika abubuwan gama gari na cutar kansa ta amfani da sabon jagorar jagorar jeri jeri don DNA methylation, jerin alamun cutar kansa na duniya kawai (UCOMs) sun fito a matsayin ƴan takara masu ƙarfi don ingantaccen kuma ingantaccen gano cutar kansa da wuri.Yayin da darajar asibiti na masu ciwon daji na yanzu ya ragu ta hanyar ƙarancin hankali da / ko ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun UCOMs suna tabbatar da sakamako mai ma'ana na asibiti.Tabbatar da yuwuwar aikin asibiti na UCOMs a cikin huhu, mahaifa, endometrial, da cututtukan urothelial yana ƙara tallafawa aikace-aikacen UCOMs a cikin nau'ikan kansar da yawa da yanayin yanayin asibiti daban-daban.A zahiri, aikace-aikacen UCOMs a halin yanzu suna ƙarƙashin bincike mai ƙarfi tare da ƙarin kimantawa a farkon gano cutar kansa, ganowar ƙarin taimako, ingancin jiyya, da sake dawowa.Hanyoyin kwayoyin da UCOMs ke gano cutar kansa sune batutuwa masu mahimmanci na gaba da za a bincika.Aiwatar da UCOMs a cikin yanayi na zahiri kuma yana buƙatar aiwatarwa da gyarawa.
KALMOMI
Gano ciwon daji;gwajin cutar kansa;DNA methylation;ciwon daji epigenetics;ciwon daji biomarkers
Me ya sa muke bukatar sabbin abubuwa cikin gaggawa biomarkers?
Bayan yaƙar kansa na fiye da ɗari ɗari, ciwon daji har yanzu shine mafi munin barazanar halitta ga ɗan adam.Ciwon daji ya kasance abin damuwa game da lafiyar duniya tare da sabbin masu kamuwa da cutar miliyan 19.3 da kuma mutuwar kusan miliyan 10 a 2020. A cikin 2020 an kiyasta sabbin cututtukan daji miliyan 4.6 a China, wanda ya kai kashi 23.7% na sabbin masu cutar kansa a duniya a cewar GLOBOCAN1.Bugu da ƙari, kusan mutuwar mutane miliyan 3 an danganta su da ciwon daji a China a cikin 2020, wanda shine kashi 30% na mutuwar da ke da alaƙa da cutar kansa a duniya1.Wadannan alkaluma sun nuna cewa, kasar Sin ce ta farko a yawan kamuwa da cutar sankara da ke mutuwa.Haka kuma, adadin tsira na ciwon daji na shekaru 5 shine 40.5%, wanda shine sau 1.5 ƙasa da adadin tsira na shekaru 5 a Amurka2,3.Kwatankwacin raguwar rayuwa da yawan mace-mace a kasar Sin fiye da kasashen da ke da ma'aunin ci gaban bil'adama sun nuna cewa, ana bukatar tsarin rigakafin cutar kansa mai inganci da tsadar gaske.Gano kansa da wuri yana ɗaya daga cikin abubuwa masu mahimmanci a cikin tsarin kiwon lafiya.Gano ciwon daji da wuri zai iya inganta hasashe da rayuwa a farkon mataki a kusan dukkanin nau'in ciwon daji4.Nasarar dabarun tantancewa sun haifar da raguwar abubuwan da suka faru da adadin mace-mace na mahaifa, nono, launin fata, da sankarar prostate.
Don cimma farkon gano cutar kansa, duk da haka, ba abu ne mai sauƙi ba.Binciken ilmin halitta da tsinkayar cutar sankara na farko, ganowa da tabbatar da amintattun alamomin ganowa da wuri, da haɓaka hanyoyin ganowa da ingantattun fasahohin gano wuri koyaushe sun kasance manyan cikas a cikin aikin4.Daidaitaccen gano ciwon daji na iya bambanta rashin lafiya daga mummunan raunuka, wanda ke taimakawa wajen guje wa hanyoyin da ba dole ba kuma yana sauƙaƙe ƙarin kula da cututtuka.Dabarun gano da wuri na yanzu sun haɗa da nazarin halittu na tushen endoscope, hoton likitanci, cytology, immunoassays, da gwaje-gwajen biomarker5-7.Kasancewa masu kutsawa da tsada, ƙwararrun biopsies na tushen endoscope suna ɗaukar nauyi mai nauyi a zahiri a matsayin babbar hanyar likita ta dogara ga ƙwararrun ma'aikata.Kamar cytology, duka hanyoyin tantancewa sun dogara da ƙwararrun likitocin kuma sun dogara ne akan hukuncin mutum tare da aikin da ya yi nisa daga manufa8.Sabanin haka, immunoassays ba daidai ba ne, da aka ba da ƙima mai inganci.Hoto na likita, azaman dabarar nunawa, yana buƙatar kayan aiki masu tsada da ƙwararrun ƙwararrun ƙwararru.Don haka, hoton likita yana da iyaka sosai saboda ƙarancin samun dama.Saboda duk waɗannan dalilai, masu gano kwayoyin halitta suna bayyana zaɓin zaɓi don gano cutar kansa da wuri.
Adalci zuwa: Yinshan Li da Wenqiang Yu
Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn
ID na ORCID: https://orcid.org/0009-0005-3340-6802 da
https://orcid.org/0000-0001-9920-1133
An karɓi Agusta 22, 2023;karba Oktoba 12, 2023;
wanda aka buga akan layi Nuwamba 28, 2023.
Akwai a www.cancerbiomed.org
©2023 Halittar Ciwon daji & Magunguna.Ƙirƙirar Commons
Lasisi-Lasisi na Ƙasashen Duniya Ba Kasuwanci 4.0
A halin yanzu ana rarraba alamomin halittu azaman sunadaran, alamomin maye gurbi na DNA, alamomin epigenetic, rashin lafiyar chromosomal, alamomin RNA waɗanda aka samo kai tsaye daga ciwace-ciwace, ko gutsuttsuran ƙari da aka samu a kaikaice daga ruwan jiki.Alamar furotin sune mafi yawan amfani da alamomin halittu a cikin gwajin cutar kansa da ganewar asali.Protein biomarkers, a matsayin masu nuna alamun halittu, an iyakance su ta hanyar halayen da za a iya shafa su ta hanyar lahani mara kyau, wanda ke haifar da bincike mai yawa da kuma wuce gona da iri, kamar yadda aka ruwaito ga α-fetoprotein da prostate-specific antigen (PSA) 9,10.Alamar RNA sun haɗa da tsarin maganganun kwayoyin halitta da sauran alamomin RNA marasa coding.Za a iya gano haɗe-haɗe na alamomin RNA ta hanyar amfani da samfuran fitsari, wanda hankalinsa ya yi nisa da gamsarwa (60%) ga ciwace-ciwacen farko, kuma gano wanda zai iya. Sauƙaƙan lalacewar yanayin RNA a cikin yanayin al'ada ya shafe shi.Alamun kwayoyin halitta da na epigenetic duka suna fuskantar matsalar yawaitar ciwace-ciwace da iyakance ga nau'ikan ciwon daji.
DNA methylation ya kasance dan takara mai karfi a matsayin mai gano kwayoyin halitta tun lokacin da Feinberg ya fara danganta shi da ciwon daji a cikin 198312. Ana lura da raguwar DNA methylation a duk matakan ciwon daji, tun farkon matakin farko.Aberrant DNA hypermethylation yawanci yana faruwa akan tsibiran CpG a cikin masu tallata kwayoyin halitta don magance masu hana ƙari13,14.Har ila yau, binciken ya nuna cewa rashin daidaituwa na DNA hypermethylation yana shiga cikin haɓakar masu kula da haɓakawa15.Kwarin methylation na DNA, wanda aka fi danganta shi da masu kula da haɓaka haɓakawa da cututtukan cututtukan hypermethylated, na iya canza yanayin bayyanar halittar zuwa yanayin da ya fi dacewa da DNA methylation kuma ya rage haɗin zuwa methylated histone H3K27me3 da haɗin gwiwar sunadaran polycomb16,17.
Daga cikin manyan adadin alamomin methylation na DNA da aka buga, da yawa sun sami nasarar yin muhawara a kasuwa;duk da haka, alamun DNA methylation da aka sayar da su a halin yanzu da bangarorin bincike har yanzu ba su buɗe yuwuwar gano cutar kansa da wuri ba saboda dalilai da yawa18.Duk da yake galibi suna nuna aikin karbuwa ta amfani da bayanan bayanai, waɗannan masu alamar halittu galibi suna yin ƙasa da kyau a cikin ainihin duniyar saboda gaskiyar cewa samfuran duniya galibi sun fi rikitarwa kuma ba a matsayin wakilai kamar waɗanda aka zaɓa a cikin bayanan ba.An nuna farkon ganowar methylation na ciwon daji da yawa na ƙarni na gaba yana da 16.8% da 40.4% kawai a cikin ciwon daji na mataki na I da II, bi da bi19.Gwajin ganowa da wuri yana buƙatar ƙarin kwanciyar hankali da ƙarin ingantattun alamomin halitta.
Gano Ciwon daji kawai (UCOM) ganowa ta amfani da jerin jagororin sakawa (GPS)
Duk da shekarun da aka yi na binciken ciwon daji, ba a sami gamsasshen rigakafi da magani ba.Ana buƙatar sabbin hanyoyin don baiwa masu bincike damar tantance cutar kansa sosai.A cikin shekaru 23 da suka gabata, alamomin cutar kansa guda 6, kamar gujewa apoptosis, mamayewar nama & metastasis, da sauransu, an faɗaɗa su zuwa 14 ta haɗa da fasalulluka kamar reprogramming epi-genetic reprogramming da polymorphic microbiomes20,21.Yayin da aka bayyana ƙarin cikakkun bayanai da suka shafi kansa, ana gabatar da ƙarin ra'ayoyi a cikin binciken ciwon daji.Binciken ciwon daji a hankali ya zo cikin wani sabon salo ta hanyoyi biyu (na kowa da kowa).Tare da haɓaka madaidaicin ilimin ciwon daji a cikin 'yan shekarun nan, mayar da hankali kan binciken ciwon daji yana karkata zuwa ga jiyya da aka yi niyya na mutum ɗaya da nau'in ciwon daji22.Don haka, kwanan nan da aka gano alamun cutar kansa sun fi mayar da hankali kan takamaiman nau'ikan kansa, kamar PAX6 mai ƙarfi kansa23 da BMP3 don kansar launi24.Ayyukan waɗannan alamomin halittu na musamman ga nau'in ciwon daji ya bambanta, amma har yanzu ba zai yiwu ga masu rauni su yi gwajin cutar kansa a lokaci ɗaya ba saboda ƙayyadaddun siyan samfuran halitta da tsadar farashi.Zai yi kyau idan za mu iya gano guda ɗaya, mai ƙarfi biomarker wanda ke da tasiri ga kowane nau'in ciwon daji a matakin kusa.
Don cimma irin wannan manufa mai ma'ana, dole ne a zaɓi mafi kyawun ɗan takarar biomarker daga jerin yuwuwar nau'ikan alamar halittu.Abubuwan da ke haifar da DNA methylation aberrations, a cikin dukkanin bayanan kwayoyin halitta da na epigenetic, an san suna da alaƙa da ciwon daji kuma wasu daga cikin na farko, idan ba na farko ba, abubuwan da ke da alaƙa da ciwon daji da ke faruwa a tsarin lokaci.Binciken DNA methylation ya fara da wuri, amma an hana shi ta hanyar rashin hanyoyin bincike.Daga cikin rukunin CpG miliyan 28 masu yuwuwar methylated a cikin kwayoyin halitta, dole ne a gano lambar da za a iya sarrafawa kuma a daidaita su zuwa kwayar halitta don ƙarin fahimtar tumorigenesis.Dukan nau'in genome bisulfite sequencing (WGBS), wanda ake la'akari da matsayin ma'aunin zinari na jerin DNA methylation, zai iya rufe kashi 50% na Cs kawai a cikin ƙwayoyin cutar kansa saboda yanayin jiyya na bisulfite wanda ke karya gutsuttsuran DNA kuma yana rage hadaddun kwayoyin halitta a lokacin. Canji na Cs-to-Ts25.Sauran hanyoyin, irin su 450k kwakwalwan kwamfuta, kawai rufe 1.6% na genome methylation.Dangane da bayanan 450k, kwamitin gano methylation na DNA yana da hankali 35.4% don nau'ikan ciwon daji na 6 na mataki na 26.Iyakance nau'ikan ciwon daji, rashin aiki mara kyau, da hayaniya da aka haifar ta hanyoyin ganowa a cikin tsarin tantancewa sun zama babban cikas ga bangarorin gano cutar sankara.
Don bincika mafi kyawun tsarin halittar sel a lokacin tumorigenesis da metastasis, mun haɓaka GPS ta musamman don gano DNA methylation mai faɗi, wanda ke rufe har zuwa 96% na rukunin CpG a cikin biliyan 0.4 reads25.GPS hanya ce ta bilateral ta hanyar amfani da 3′ ƙarshen DNA guntuwar methyl-cytosines mara canzawa bayan jiyya na bisulfite wanda ke jagorantar daidaita lissafin DNA methylation na ƙarshen 5′ ta hanyar jeri-ƙarshen biyu (Hoto 1)25.Madaidaicin jagorar methyl-cytosine, yana aiki azaman madaidaicin samfuri, yana taimakawa cikin daidaitawar yanki mai girma-GC wanda ke dawo da mafi yawan bayanan jeri na WGBS na gargajiya.Babban fasalin abin rufe fuska na GPS yana ba da adadi mai yawa na bayanan methylation na DNA, wanda ke ba mu damar bincika bayanan martabar methylation na kansa tare da ƙuduri mafi girma a yankunan da ba a yi bincike a baya ba.
GPS tana ba mu kayan aiki mai ƙarfi don bincika kamannin ciwon daji, wanda zai iya sauƙaƙa bincike kan kansa sosai da yuwuwar samun bayani na duniya game da tumɓin-origenesis da metastasis.Yayin da ake nazarin bayanan GPS na layukan ƙwayoyin cutar kansa, an sami sabani na musamman akai-akai.Akwai yankuna da yawa waɗanda suka bayyana suna da ƙarancin hypermethylated a cikin nau'ikan samfuran ciwon daji da yawa.Wannan binciken ba zato ba tsammani daga baya an inganta shi don yin aiki azaman UCOMs.Fiye da samfurori 7,000 daga nau'ikan ciwon daji guda 17 a cikin Cibiyar Cancer Genome Atlas (TCGA) an bincikar su, daga cikin abin da muka gano UCOM na farko, HIST1H4F, kwayar halitta mai alaka da tarihi wanda ke da hypermethylated a cikin kowane nau'in ciwon daji27.An samo jerin UCOMs kuma an inganta su a cikin bayanan TCGA, Gene Expression Omnibus (GEO), da kuma samfurori na asibiti na ainihi.Har zuwa yanzu, an samo HIST1H4F, PCDHGB7, da SIX6 kuma an inganta su azaman UCOMs.Binciken da ba zato ba tsammani na UCOMs yana ba da amsa mai ƙarfi ga buƙatar gano cutar kansa da wuri.UCOMs suna ba da mafita don gano alamar guda ɗaya na cututtukan daji da yawa.
Halayen UCOMs
Bayan tabbatarwa, an nuna UCOMs don nuna manyan halaye guda huɗu waɗanda ke ba UCOMs damar wuce ingancin samfuran halittu na yanzu (Hoto 2).
Musamman ga malignancy
UCOMs sun keɓanta ga cututtukan daji ko pre-ciwon daji kuma canje-canjen ilimin lissafi na yau da kullun bai shafe su ba.Wasu alamomin da ke da alaƙa da ciwon daji na yanzu waɗanda aka yi amfani da su sosai a farkon ganowa da/ko nunawa sun haifar da ƙarin bincike.Maɗaukakin matakan PSA, kayan aikin tantancewa na asibiti, ana kuma gano su a cikin yanayi mara kyau, irin su prostate hyperplasia da prostatitis10.Ciwon bincike da yawa da sakamakon wuce gona da iri yana haifar da raguwar ingancin rayuwa saboda hanji, fitsari, da matsalolin jima'i28.Sauran tushen furotin da masu amfani da kwayoyin halitta da yawa a cikin tsarin asibiti, kamar CA-125, ba su haifar da wani fa'ida mai mahimmanci ba yayin da suke haifar da ƙari da ƙari29.Babban ƙayyadaddun ƙayyadaddun UCOMs don ɓarna yana guje wa waɗannan gajerun abubuwan.UCOM, PCDHGB7, da kyau yana bambanta manyan cututtukan intraepithelial squamous (HSILs) da ciwon daji na mahaifa daga samfuran al'ada da ƙananan raunuka na intraepithelial (LSILs), yayin da yawancin sauran alamomin halittu zasu iya bambanta kansar mahaifa daga samfuran al'ada30.Ko da yake PCDHGB7 ba ta gano bambance-bambance masu mahimmanci tsakanin endometrium na al'ada da hyperplasia na endometrial ba, ana gano bambance-bambance masu mahimmanci tsakanin endometrium na al'ada da hyperplasia na yau da kullum, har ma an gano bambance-bambance tsakanin al'ada na endometrium da ciwon daji na endometrial (EC) bisa PCDHGB731.UCOMs sun keɓanta ga munanan raunuka a cikin bayanan bayanai da samfuran asibiti.Daga hangen nesa na majiyyaci, UCOMs na musamman suna rage kofa don fahimtar hadaddun alamu na nau'ikan alamomin marasa ƙarfi marasa ƙarfi da damuwa mai ma'ana yayin aikin tantancewa.Daga mahangar likitanci, UCOMs na musamman sun bambanta malignancies daga raunuka mara kyau, waɗanda ke taimakawa a cikin bambance-bambancen marasa lafiya kuma suna rage hanyoyin kiwon lafiya da ba dole ba da ƙari.Sabili da haka, UCOMs na musamman suna rage raguwar tsarin kiwon lafiya, kawar da ɓacin rai, da samar da ƙarin albarkatu na likitanci ga mabukata.
Hoto 1 Tsarin aikin GPS don gano DNA methylation25.Layin launin toka: shigar da jerin DNA;jan layi: DNA da aka bi da T4 DNA polymerase, maye gurbin cytosine tare da 5'-methylcytosine a ƙarshen 3' na shigarwa;blue C tare da Ni: methylated cytosine;blue C: cytosine unmethylated;rawaya T: thymine25.
Duk ko ba komai
UCOMs suna nan a cikin ƙwayoyin kansa kawai kuma ana gano su sosai a kusan dukkanin ƙwayoyin cutar kansa.An inganta HIST1H4F don zama hypermethylated a kusan dukkanin nau'in ciwon daji amma ba a cikin samfurori na al'ada27 ba.Hakazalika, PCDHGB7 da SIX6 kuma an nuna su suna hypermethylated a duk samfuran ƙari amma ba a cikin samfuran al'ada30-32 ba.Wannan sifa ta musamman tana haɓaka aikin UCOMs sosai dangane da iyakar ganowa da hankali.Kimanin kashi 2% na kwayoyin cutar kansa za a iya bambanta su a cikin samfurori, yana sa UCOMs ya zama mafi mahimmancin biomarker fiye da yawancin masu amfani da kwayoyin halitta30. A matsayin mai amfani da kwayoyin halitta da aka yi amfani da shi don gano ciwon daji na launin fata, maye gurbin KRAS ya kasance kawai a cikin kusan 36% na ciwon daji na colorectal. yana ba da shawarar rashin iya gano cutar33.Karancin yaɗuwar maye gurbi na KRAS a cikin ciwon daji na launin fata yana iyakance KRAS a hade tare da sauran alamomin halitta.A haƙiƙa, haɗaɗɗun alamomin halittu na iya da alama mai ban sha'awa da farko, amma ba koyaushe yana haifar da sakamako mai gamsarwa ba yayin da yake nuna ƙarar ƙara a cikin binciken ganowa kuma yawanci ya haɗa da hanyoyin gwaji masu rikitarwa.Sabanin haka, PCDHGB7 da sauran UCOMs sun kasance a cikin duk cututtukan daji.UCOMs suna gano abubuwan da ke haifar da cutar kansa a cikin nau'ikan samfuran kansar daban-daban tare da madaidaicin madaidaicin yayin kawar da hadaddun hanyoyin bincike na soke amo.Ba shi da wahala a gano ciwon daji a cikin samfuri mai yawa, amma yana da matuƙar ƙalubale don gano ciwon daji a cikin ƙaramin samfurin.UCOMs suna iya gano ƙananan ƙwayar cutar kansa.
Hoto 2 Halayen UCOMs.
Gano ciwon daji kafin canje-canjen pathological
Ana iya gano UCOMs a cikin matakin pre-ciwon daji kafin canje-canjen cututtuka.A matsayin masu nazarin halittu na epigenetic, abubuwan rashin daidaituwa na UCOM suna faruwa a cikin matakin farko fiye da abubuwan da ba a saba gani ba kuma ana iya gano su a duk cikin tumorigenesis, ci gaba, da metastasis34,35.Hankalin UCOM akan lokaci yana haɓaka aikin UCOM a cikin gano ciwon daji na farko da raunukan da suka rigaya.Gano ciwon daji na farko bisa ga biopsies da cytology na iya zama da wahala ga ko da ƙwararrun ƙwararrun ƙwararrun ƙwayoyin cuta.An ba da rahoton biopsy guda ɗaya da aka samu ta hanyar colposcopy a matsayin tabbatacce a cikin 60.6% na samfuran HSIL+.Ana buƙatar ƙarin biopsies don raunuka da yawa don ƙara hankali36.Sabanin haka, UCOM, PCDHGB7, yana da azanci na 82% don samfuran HSIL +, wanda ya zarce hankalin biopsies da mafi yawan masu biomarkers30.Alamar methylation, FAM19A4, yana da hankali na 69% don CIN2+, wanda yayi kama da cytology, amma ba zai iya bambanta CIN1 daga samfurori na al'ada37 ba.An nuna UCOMs sun kasance mafi mahimmancin gano ƙwayoyin halitta da wuri.Idan aka kwatanta da ƙwararrun masana ilimin ƙwayoyin cuta, UCOMs suna da ƙwarewar ganowa ga cututtukan daji na farko, wanda hakan ke ba da gudummawa ga ingantacciyar hasashen cutar kansa da rayuwa30.Bugu da ƙari, UCOMs suna ba da dandamalin ganowa wanda ke isa ga wuraren da ba su da ƙwararrun likitocin cuta kuma suna haɓaka haɓakar ganowa sosai.Tare da yin samfuri iri ɗaya da hanyoyin ganowa, gano UCOM yana haifar da tabbataccen sakamako mai sauƙin fassara wanda ya fi dacewa da ƙa'idar tantancewa da ke buƙatar ƙwararrun ma'aikata da albarkatun likita.
Sauƙi don ganowa
Hanyoyi na yanzu don gano DNA methylation suna da rikitarwa kuma suna ɗaukar lokaci.Yawancin hanyoyin suna buƙatar canji na bisulfite, wanda ke haifar da asara a cikin ingancin samfurin kuma mai yiwuwa ya haifar da rashin daidaituwa da sakamako mara kyau.Rashin haɓaka mara kyau da aka haifar ta hanyar jiyya na bisulfite na iya haifar da rudani ga likitoci da marasa lafiya da kuma ƙara tsoma baki tare da bin hanyoyin da / ko hanyoyin magani.Sabili da haka, mun ƙara canza hanyar gano UCOM don guje wa matsala ta bisulfite na samfuran, daidaita buƙatun aikace-aikacen asibiti, da haɓaka samun dama.Mun ƙirƙira wata sabuwar hanya ta amfani da methylation-m ƙuntatawa enzymes haɗe tare da ainihin-lokaci fluorescent quantitative PCR (Me-qPCR) don ƙididdige matsayin methylation na UCOMs a cikin 3 h ta amfani da hanyoyi masu sauƙi (Hoto 3).Me-qPCR na iya ɗaukar nau'ikan samfuri da yawa, kamar tarin magunguna na asibiti da samfuran fitsari da aka tattara da kansu.Za a iya sarrafa samfuran asibiti da aka tattara, adana, da kuma ci gaba cikin sauƙi zuwa ganowa ta amfani da daidaitattun kuma cire DNA mai sarrafa kansa.Ana iya amfani da DNA ɗin da aka cire kai tsaye zuwa dandalin Me-qPCR don amsawar tukunya ɗaya da sakamakon ƙididdigewa.Bayan binciken sakamako mai sauƙi ta amfani da samfuran bincike waɗanda aka dace kuma an inganta su zuwa takamaiman nau'ikan ciwon daji, ana fassara ƙudurin ƙarshe na sakamakon gano UCOM kuma an gabatar da shi azaman ƙimar ƙima.Dandalin Me-qPCR ya fi dacewa da bisulfite-pyrosequencing na gargajiya a cikin gano UCOM yayin da yake adana 3 h ofbisulfite canzawa, bisa ga ka'idar EZ DNA Methylation-Gold kit.Sabbin dandamalin gano methylation yana sa ganowar UCOM ya tsaya tsayin daka, mafi daidaito, kuma mafi samun dama30.
Hoto 3 Tsarin Ganewa na UCOMs.Nau'in samfurin sun haɗa da ƙwararrun samfur BALF, goge Pap, da/ko fitsarin da aka tattara.Ana iya ɗaukar tsarin hakar DNA zuwa mai cirewa ta atomatik, samfurin wanda qPCR zai iya gano shi kai tsaye.
Abubuwan da aka bayar na UCOMs
Ciwon daji na huhu
Ciwon daji na huhu shine na biyu mafi yawan kamuwa da cutar kansa kuma mafi yawan cutar kansa a duniya, wanda ya kai kashi 11.4% na sabbin masu kamuwa da cutar da kashi 18.0% na sabbin mace-mace1.Daga cikin dukkan cututtukan da aka gano, 85% sune wadanda ba ƙananan ƙwayoyin huhu ba (NSCLC) da 15% ƙananan ciwon huhu ne (SCLC), wanda ke da matsayi mafi girma na malignancy38.Ƙididdigar ƙididdiga marasa ƙima (LDCT) ita ce hanyar da aka ba da shawarar a halin yanzu don ciwon huhu na huhu kuma an nuna shi don inganta ganowa da wuri da kuma rage mace-mace6;duk da haka, saboda ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun damar, LDCT har yanzu ba ta yi aiki azaman hanyar tantancewa mai gamsarwa ba, kamar yadda sauran alamomin ciwon daji ke yi, kamar CEA39.Farashin da yuwuwar binciken binciken da aka rasa da kuskuren dabarun tantancewar LDCT suna hana ci gaban gwajin cutar kansar huhu40.HIST1H4F, UCOM, yana da babban yuwuwar azaman farkon gano ƙwayoyin halitta a cikin samfuran ruwan bronchoalveolar (BALF)27.HIST1H4F yana da hypermethylated a cikin huhu adenocarcinoma da huhu squamous cell carcinoma, tare da ƙayyadaddun ganowa na 96.7% da azanci na 87.0% (Hoto 4A), da kuma kyakkyawan aiki don mataki na ciwon daji27.HIST1H4F yana da takamaiman 96.5% da hankali na 85.4% don NSCLC, da 96.5% da 95.7%, bi da bi, don SCLC27.Bugu da ƙari, samfurori na wasu nau'in ciwon daji guda takwas, ciki har da pancretic da ciwon daji na launi, sun tabbatar da cewa HIST1H4F yana da hypermethylated a cikin dukkanin nau'i takwas27.
Ciwon daji na mahaifa
Ciwon daji na mahaifa shi ne na hudu da aka fi samun cutar kansa da aka fi sani da kansa kuma shi ne na hudu da ke haifar da mace-mace a cikin mata a shekarar 2020, wanda ya kai kashi 3.1% na sabbin masu kamuwa da cutar da kashi 3.4% na mace-mace masu alaka da kansa a duniya1.Don kawar da kansar mahaifa nan da shekarar 2030, kamar yadda WHO ta tsara, gano cutar kansar mahaifa da wuri ya zama dole.Idan an gano shi a farkon matakin, adadin tsira na shekaru 5 ya kai kashi 92% tare da ciwon daji na mahaifa41.Jagororin Ƙungiyar Ciwon daji ta Amirka (ACS) suna ba da shawarar gwajin cytology na mahaifa, gwajin HPV na farko, ko kuma cotests don nunawa42.Cytology na mahaifa yana da ɓarna kuma yana iya gano 63.5% kawai na lokuta CIN2+37.
PCDHGB7, akasin haka, ya yi aiki mafi kyau ta amfani da Pap smears da ɓoye na farji, kuma yana iya bambanta HSIL da LSIL da kyau a cikin matakin farko-farko.PCDHGB7 kadai yana da hankali na 100.0% da ƙayyadaddun 88.7% don ciwon mahaifa (Hoto 4B), da kuma 82.1% hankali da 88.7% ƙayyadaddun HSIL+ samfurori30.Har ila yau PCDHGB7 yana da 90.9% hankali da kuma 90.4% musamman a cikin samfurori na ɓoye na farji don ciwon mahaifa, wanda ya fi sauƙi a tattara30.Lokacin da aka haɗa tare da babban haɗari (hr) gwajin HPV ko Thinprep Cytology Test (TCT), PCDHGB7 yana da haɓakar hankali na 95.7% da ƙayyadaddun 96.2%, wanda ya zarce na gwajin hrHPV (20.3%), TCT (51.2%) ), da kuma biyun sun haɗu (57.8%) don kansar mahaifa30.Hakanan an nuna PCDHGB7 yana da hypermethylated a cikin nau'ikan ciwon daji guda 17 daga bayanan TCGA, yana nuna dacewarta a cikin dangin UCOM30.
Hoto 4 UCOMs an inganta su a cikin nau'ikan ciwon daji guda huɗu a cikin manyan karatun asibiti.A. Ayyukan HIST1H4F, UCOM, a cikin gano ciwon daji na huhu na samfurori 508.B. Ayyukan PCDHGB7, UCOM, a cikin gano ciwon daji na mahaifa na samfurori 844.C. Ayyukan PCDHGB7, UCOM, a cikin gano ciwon daji na endometrial na 577 endometrial Pap da Tao brush samfurori.D. Ayyukan SIX6, UCOM, a cikin gano ciwon daji na urothelial na samfurori 177.
EC
EC tana daya daga cikin cututtukan daji da aka fi sani da tsarin haihuwa na mata a duk duniya, tare da kiyasin sabbin masu kamuwa da cutar miliyan 4.2 da kashi 1% na mace-mace masu alaka da cutar kansa kowace shekara1.Tare da samun nasarar ganewar asali a matakin kusa, EC yana iya warkewa kuma yana da adadin rayuwa na shekaru 5 na 95% don ciwon daji na mataki na farko.Marasa lafiya waɗanda ke da alamun bayyanar cututtuka, irin su zubar da jini mara kyau na mahaifa, suna karɓar kimantawa na lokaci-lokaci na asibiti kuma suna yin ɓarna da hanyoyin biopsy masu raɗaɗi, duk da kawai 5% -10% a ƙarshe suna haɓaka EC43.Sautin ultravaginal, azaman hanyar ganowa gama gari, ba ta da wani abin dogaro sosai saboda rashin iya bambance rashin lafiya daga muggan canje-canje na ƙarshe da ƙimar ƙimar ƙarya44.
An gudanar da kwatankwacin kwatancen magani CA-125, EC biomarker da aka fi amfani da shi, da PCDHGB7.Serum CA-125 yana da hankali na 24.8%, wanda ke nuna cewa CA-125 alama ce marar isa ga EC duk da ƙayyadaddun 92.3% 31.Gano PCDHGB7 ta amfani da samfuran goga na Pap ya haifar da azanci na 80.65% da ƙayyadaddun 82.81% don matakan ECatall, yayin da goga na Tao yana da azanci na 61.29% da ƙayyadaddun 95.31%31.Samfurin bincike na PCDHGB7, dangane da Me-qPCR, ya haifar da azanci na 98.61%, ƙayyadaddun 60.5%, da cikakkiyar daidaito na 85.5%, ta amfani da samfuran goge Pap da Tao (Hoto 4C)31.
Urothelial ciwon daji
Ciwon daji na urothelial, wanda ya ƙunshi mafitsara, ƙashin ƙashin ƙugu, da ciwon ureter, shine na bakwai mafi yawan kamuwa da cutar daji a cikin 2020 a duk duniya, wanda ya haifar da 5.2% na sababbin lokuta da 3.9% na mace-mace1.Ciwon daji na urothelial, wanda sama da kashi 50% na ciwon daji ne na mafitsara, sune na huɗu mafi yawan kamuwa da cutar kansa a Amurka a cikin 2022, wanda ke da kashi 11.6% na sabbin cututtukan da aka gano3.Kusan kashi 75% na ciwon daji na mafitsara an rarraba su azaman ciwon mafitsara mara tsoka wanda aka iyakance ga mucosa ko submucosa45.Cystoscopy biopsy shine ma'auni na zinariya don bincikar ciwon urothelial wanda aka aiwatar ta hanyar fluorescence in situ hybridization (FISH) da gwaje-gwajen cytology.KIFI da cytology suna da rashin aikin bincike mara kyau, kuma cystoscopy yana da kutse kuma yana da haɗarin ɓarnawar ƙananan ƙwayoyin cuta, ɓarna ɓarna, da yuwuwar haifar da yaduwa ko sake dawowa daga cutar kansa46.An kuma nuna cewa UCOM da aka inganta a baya, PCDHGB7, an kuma nuna cewa yana da hypermethylated a cikin ciwon daji na urothelial, tare da yanki a ƙarƙashin 0.86, yana ba da shawarar yuwuwar iya ganowa30.Don ƙara inganta ƙarin UCOMs kuma mafi kyawun saukar da nau'ikan samfura, an bincika SIX6, sabon labari UCOM, kuma ya nuna kyakkyawan yuwuwar ganowa a farkon gano cutar kansar urothelial ta amfani da samfuran fitsari akan dandamali na Me-qPCR.Gano SIX6 ta amfani da samfuran fitsari ya nuna ƙwarewar gasa na 86.7% da ƙayyadaddun 90.8% (Hoto 4D), yayin da ba mai haɗari ba kuma mai sauƙin samun32.Ƙimar SIX6 a cikin sa ido na metastasis da kimanta ingancin jiyya a halin yanzu ana kan bincike.
Gaba da kalubale
UCOMs suna da aiki mai ƙarfi a cikin yuwuwar gano cutar kansa da yawa, amma akwai sauran aiki da yawa da za a yi.Mun kasance muna faɗaɗa jerin UCOMs kuma muna haɓaka UCOMs a cikin ƙarin nau'ikan ciwon daji, gami da waɗanda ke da wahalar ganowa a al'adance.Sakamakon tabbatarwa daga bayanan bayanan TCGA sun ƙara tabbatar da aikace-aikacen UCOMs a cikin ƙarin nau'ikan ciwon daji da ƙarin yanayi.A cikin bincike na farko, an nuna UCOMs suna da yuwuwar bincike mai ƙarfi don cholangiocarcinomas da pancreatic adenocarcinomas, waɗanda kusan ba zai yiwu a tantance su ba a matakin kusa da hanyoyin nunawa na yanzu32,47.Ana iya amfani da ikon gano cututtukan daji masu wuya tare da UCOMs tare da DNA ƙari mai yawo (ctDNA) ta ingantaccen dandamalin biopsy na ruwa48.Wani binciken da ya ƙunshi kwamitin gano cutar sankara na DNA na plasma ya haifar da azanci na 57.9%49.Duk da ƙayyadaddun ƙayyadaddun ƙayyadaddun ƙayyadaddun ayyuka, aikin gabaɗaya ya nuna cewa har yanzu akwai sauran damar ingantawa.
Siffofin musamman na UCOMs kuma sun goyi bayan binciken yuwuwar UCOM a cikin ƙimar ingancin jiyya da sake dawowa.Bisa ga Ma'auni na Ƙididdigar Amsa a cikin Tumors (RECIST), hoton likita shine hanyar da aka ba da shawarar don sake dawowa da kuma kimanta ingancin jiyya, yayin da ake amfani da alamomin ƙari kadai don kimanta50.A zahiri, duk da haka, hanyoyin yin hoto suna da tasiri sosai ta mita da lokaci, sabili da haka fallasa marasa lafiya zuwa babban haɗari da farashi51,52.An inganta SIX6 don yin aiki a matsayin mai tsinkaya ga ciwon nono metastasis32.Kulawar ctDNA na tushen ruwa mai ruwa yana ba da damar sa ido na ainihin-lokaci akan ƙarancin cututtukan da suka rage watanni kafin ganowar rediyo, daidaitaccen jinkirta da hana ci gaban ciwon daji mai alaƙa53.Sakamakon farko ya nuna cewa UCOMs suna nuna matakin hypermethylation na ciwon daji a ainihin lokacin nan da nan bayan tiyata da magani32.Babban hazaka da UCOMs ke nunawa da kuma amfani a cikin nau'ikan samfuran da ba su da alaƙa da yawa suna ba UCOMs damar yin aiki a matsayin madaidaicin maimaituwa mai kula da biomarker yayin kiyaye babban bin haƙuri.
Haka kuma, samun damar jama'a ga gwajin wani babban batu ne da ke buƙatar ƙarin ƙoƙari.Yayin da aka karɓi haɗin gwiwar gano UCOM a cikin ƙarin asibitoci a cikin bege na amfana da ƙarin marasa lafiya, an gudanar da bincike da bincike sosai a cikin karkarar China.UCOMs na buƙatar ingantacciyar dama don cancanta azaman kayan aikin tantancewa, musamman ga wuraren da ba a haɓaka ba.
Yayin da sakamakon aikace-aikacen UCOM a farkon ganowa yana da alƙawarin, yawancin abubuwan da ba a sani ba game da UCOM sun wanzu.Tare da bincike mai aiki, ƙarin bincike yana da garantin game da dalilin da yasa UCOMs ke kasancewa a duniya baki ɗaya a cikin cututtukan daji.Hanyoyin ƙa'idodin ƙa'idar epigenetic da ke ƙarƙashin UCOMs sun cancanci ƙarin bincike, wanda zai iya ba da hujjar sabon jagora don maganin ciwon daji.Komawa ga hulɗar tsakanin ƙwayar ƙwayar cuta da nau'in nau'in ƙwayar cuta, muna sha'awar dalilin da yasa UCOMs na iya zama keɓantawa ga yawancin masu ciwon daji waɗanda ke da alaƙa da takamaiman nau'in ciwon daji.Matsayin da aka gano DNA methylation aberrations na UCOM a cikin tumorigenesis, ci gaban ƙari, da metastasis ba a ƙayyade ba a cikin aiwatar da asarar da dawo da asalin tantanin halitta kuma yana buƙatar cikakken dubawa.Wani babban abin sha'awa ya ta'allaka ne a cikin iyakokin hadewar dabi'ar kama-karya ta UCOMs tare da alamomi na musamman na nama a cikin bege na gabatowa daidai gano alamun cutar kansa da gano asalin ƙwayar ƙwayar cuta ta hanyar juyawa.UCOMs na iya zama ingantaccen kayan aiki don hana kansa, gano kansa, da yuwuwar kare da kawar da kansa.
Ba da tallafi
Wannan aikin ya sami goyon bayan shirin R&D na kasa na kasar Sin (Grant No. 2022BEG01003), gidauniyar kimiyyar dabi'a ta kasar Sin (Grant Nos. 32270645 da 32000505), ba da tallafi daga Hukumar Lafiya ta lardin Heilongjiang (Grant No. 2020-111) , da kuma Tallafi daga Cibiyar Kimiyya da Fasaha ta Heze (Grant No. 2021KJPT07).
Bayanin rikice-rikice na sha'awa
Wei Li shine Daraktan R&D na Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu yana hidima a Hukumar Ba da Shawarar Kimiyya ta Epiprobe.W. Yu da Epiprobe sun amince da haƙƙin mallaka masu alaƙa da wannan aikin.Duk sauran marubutan ba su bayyana buƙatun gasa ba.
Gudunmawar marubuci
An tsara da kuma tsara aikin: Chengchen Qian da Wenqiang Yu.
Ya rubuta takarda: Chengchen Qian.
An yi misalan: Chengchen Qian.
An yi bita tare da gyara rubutun: Xiaolong Zou, Wei Li, Yinshan Li da Wenqiang Yu.
Magana
1. Sung H, Ferlay J, Siegel RL, LaversanneM, Soerjomataram I, Jemal A, et al.Kididdigar Ciwon daji na Duniya 2020: Ƙididdiga na GLOBOCAN
abubuwan da suka faru da mace-mace a duniya don cututtukan daji 36 a cikin ƙasashe 185.CA Cancer J Clin.2021;71: 209-49.
2. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al.Kididdigar cutar daji a China da Amurka, 2022: bayanan martaba, abubuwan da suka faru, da masu tantancewa.Chin MedJ (Ingilishi).2022;135: 584-90.
3. Siegel RL, Miller KD, WagleNS, JemalA.Kididdigar ciwon daji, 2023. CA Ciwon daji J Clin.2023;73: 17-48.
4. Crosby D, BhatiaS, Brindle KM, Coussens LM, Dive C, Emberton M, et al.Gano kansa da wuri.Kimiyya.2022;375: ku 9040.
5. Ladabaum U, Dominitz JA, KahiC, Schoen RE.Dabarun don
duban ciwon daji na colorectal.Gastroenterology.2020;158: 418-32.
6. Tanoue LT, Tanner NT, Gould MK, Silvestri GA.Binciken cutar kansar huhu.Am J Respira Crit Care Med.2015;191: 19-33.
7. Bouvard V, WentzensenN, Mackie A, Berkhof J, BrothertonJ, Giorgi-Rossi P, et al.Halin IARC akan gwajin cutar kansar mahaifa.N EnglJ Med.2021;385: 1908-18.
8. Xue P, Ng MTA, QiaoY.Kalubalen colposcopy don gwajin cutar kansar mahaifa a cikin LMICs da mafita ta hanyar hankali na wucin gadi.BMC Med.2020;18:169.
9. Johnson P, Zhou Q, Dao DY, Lo YMD.Masu zagawa da biomarkers a cikin ganewar asali da kula da ciwon hanta.Nat Rev Gastroenterol Hepatol.2022;19: 670-81.
10. Van PoppelH, Albreht T, Basu P, HogenhoutR, CollenS, Roobol M. Serum PSA na farko da aka gano da ciwon daji na prostate a Turai da kuma duniya: baya, yanzu da kuma gaba.Na Rev Urol.2022;19:
562-72.
11. HolyoakeA, O'Sullivan P, Pollock R, Best T, Watanabe J, KajitaY,
da al.Haɓaka gwajin fitsari na multiplex RNA don ganowa da daidaitawar carcinoma cell cell carcinoma na mafitsara.Clin Cancer Res.2008;14: 742-9.
12. Feinberg AP, Vogelstein B. Hypomethylation yana bambanta kwayoyin halittar wasu cututtukan daji na mutum daga takwarorinsu na yau da kullun.Yanayi.1983;301: 89-92.
13. Ng JM, Yu J. Promoter hypermethylation na ƙwayoyin cuta masu hana ƙwayar cuta a matsayin masu yiwuwar biomarkers a cikin ciwon daji na colorectal.IntJ Mol Sci.2015;16: 2472-96.
14. Esteller M. Ciwon daji epigenomics: DNA methylomes da taswirar gyare-gyare na tarihi.Na Rev Genet.2007;8: 286-98.
15. Nishiyama A, Nakanishi M. Kewaya yanayin yanayin DNA methylation na ciwon daji.Trends Genet.2021;37: 1012-27.
16. Xie W, Schultz MD, ListerR, Hou Z, Rajagopal N, Ray P, et al.Nazarin Epigenomic na bambance-bambancen nau'ikan nau'ikan nau'ikan nau'ikan ƙwararrun ɗan adam.Cell.2013;153: 1134-48.
17. Li Y, Zheng H, Wang Q, Zhou C, WeiL, Liu X, da dai sauransu.Bincike-fadi-fadi na genome yana bayyana rawar Polycomb wajen haɓaka hypomethylation na kwarin methylation na DNA.Genome Bio.2018;19:18 .
18. Koch A, JoostenSC, Feng Z, de Ruijter TC, DrahtMX, MelotteV,
da al.Binciken DNA methylation a cikin ciwon daji: wurin da aka sake duba.Nat Rev Clin Oncol.2018;15: 459-66.
19. KleinEA, Richards D, Cohn A, TummalaM, Lapham R, Cosgrove D, et al.Tabbatarwa na asibiti na gwajin gano cutar kansa da farko na tushen methylation da aka yi niyya ta amfani da saitin tabbatarwa mai zaman kansa.Ann Oncol.2021;32: 1167-77.
20. Hanahan D, Weinberg RA.Alamomin cutar daji.Cell.2000;100: 57-70.
21. Hanahan D. Alamomin ciwon daji: sababbin girma.Cancer Discov.2022;12: 31-46.
22. Schwartzberg L, Kim ES, Liu D, Schrag D. Daidaitaccen oncology: wanene, ta yaya, menene, yaushe, kuma yaushe?Am Soc Clin Oncol Educ Littafin.2017: 160-9.
23. Liu H, Meng X, Wang J. Ainihin adadin methylation
gano kwayar halittar PAX1 a cikin gwajin cutar kansar mahaifa.IntJ Gynecol Cancer.2020;30: 1488-92.
24. Imperiale TF, RansohoffDF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al.Gwajin DNA na Multitargetstool don gwajin cutar kansa mai launi.N EnglJ Med.2014;370: 1287-97.
25. Li J, Li Y, Li W, Luo H, Xi Y, Dong S, da dai sauransu.Matsayin jagora
jeri yana gano tsarin methylation na DNA wanda ke canza asalin tantanin halitta da cibiyoyin sa ido kan ƙwayoyin cuta.Genome
Res.2019;29: 270-80.
26. Gao Q, LinYP, Li BS, Wang GQ, Dong LQ, Shen BY, et al.Ganewar ciwon daji da yawa mara ƙima ta hanyar kewaya DNA methylation sequencing (THUNDER): haɓakawa da nazarin tabbatarwa mai zaman kansa.Ann Oncol.2023;34: 486-95.
27. Dong S, Li W, Wang L, Hu J, Song Y, Zhang B, et al.Kwayoyin da ke da alaƙa da Histone suna hypermethylated a cikin ciwon huhu da kuma hypermethylated
HIST1H4F na iya ba da alamar cutar daji ta asa pan-cancer.Ciwon daji Res.2019;79: 6101-12.
28. HeijnsdijkEA, Wever EM, AuvinenA, Hugosson J, Ciatto S, Nelen V, et al.Tasirin ingancin rayuwa na takamaiman antigen prostate.N EnglJ Med.2012;367: 595-605.
29. Luzaka, Schneh-Inshagrst P, Bün S, Mayer-Zitarosa A, Siebert U. Clinical tasiri na ciwon daji gwajineded a matsayin hidimar kiwon lafiya: bita tsari.Eur J Lafiyar Jama'a.2016;26: 498-505.
30. Dong S, Lu Q,Xu P, Chen L, Duan X, Mao Z, et al.
Hypermethylated PCDHGB7 azaman cutar kansa kawai ta duniya da aikace-aikacen sa a farkon gwajin cutar kansar mahaifa.Clin Transl Med.2021;11: e457.
31. Yuan J, Mao Z, Lu Q,Xu P, Wang C, Xu X, et al.PCDHGB7 Hypermethylated a matsayin mai alamar biomarker don ganowa da wuri na ciwon daji na endometrial a samfuran goga na endometrial da gogewar mahaifa.Gaban Mol Biosci.2022;8: 774215.
32. Dong S, Yang Z,Xu P, Zheng W, Zhang B, Fu F, da dai sauransu.Juna
gyare-gyare na musamman na epigenetic akan SIX6 tare da hypermethylation don matakin precancer da gano bayyanar metastasis.Canjin Siginar Target Ther.2022;7:208 .
33. Huang L, Guo Z, Wang F, Fu L. KRAS maye gurbi: daga marasa lafiya zuwa magunguna a cikin ciwon daji.Canjin Siginar Target Ther.2021;6:386.
34. Belinsky SA, Nikula KJ, PalmisanoWA, MichelsR, SaccomannoG, GabrielsonE, et al.Aberrant methylation na p16 (INK4a) abu ne mai kusantar faruwa a cikin ciwon huhu na huhu da kuma yuwuwar biomarker don ganewar asali.Proc Natl Acad Sci U SA.1998;95: 11891-6.
35. Robertson KD.DNA methylation da cutar mutum.Na Rev Genet.2005;6: 597-610.
36. WentzensenN, Walker JL, Gold MA, Smith KM, ZunaRE,
Mathews C, et al.Biopsies da yawa da gano abubuwan da suka faru na kansar mahaifa a colposcopy.J Clin Oncol.2015;33: 83-9.
37. De Strooper LM, Meijer CJ, Berkhof J, Hesselink AT, Snijders
PJ, Steenbergen RD, et al.Binciken Methylation na FAM19A4
Halittar kwayoyin halittar mahaifa a cikin guntun mahaifa yana da inganci sosai wajen gano mahaifa
carcinomas da ci-gaba CIN2/3 raunuka.Ciwon daji Prev Res (Phila).2014;7: 1251-7.
38. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS.Ciwon daji na huhu.Lancet.2021;398: 535-54.
39. Grunnet M, Sorensen JB.Carcinoembryonic antigen (CEA) azaman alamar ƙari a cikin ciwon huhu.Ciwon huhu.2012;76: 138-43.
40. Wood DE, KazerooniEA, Baum SL, EapenGA, EttingerDS, Hou L, et al.Binciken Ciwon Huhu, Siffar 3.2018, NCCN Dokokin Ayyuka na Clinical a Kan Oncology.J Natl Compr Canc Netw.2018;16: 412-41.
41. American Cancer Society.Bayanan cutar daji & adadi.Atlanta, GA, Amurka: Ƙungiyar Ciwon Kankara ta Amirka;2023 [an sabunta 2023 Maris 1;aka buga 2023 Agusta 22].
42. FonthamETH, Wolf AMD, Church TR, EtzioniR, Flowers CR,
Herzig A, et al.Binciken kansar mahaifa ga mutane a matsakaicin haɗari: 2020 sabuntawar jagora daga Ƙungiyar Ciwon daji ta Amurka.CA Cancer J Clin.2020;70: 321-46.
43. Clarke Ma, Del Mar, Arbyn M Morilloa, Arbyn M Morilloa, Bakkumar M Morilloa, Bakkumar N. Kungiyar Hadarin N.JAMA Intern Med.2018;178: 1210-22.
44. Jacobs I, Gentry-Maharaja, Burnell M, ManchandaR, Singh N,
Sharma A, et al.Hankali na gwajin duban dan tayi na transvaginal
don ciwon daji na endometrial a cikin matan postmenopausal: nazarin kula da shari'a a cikin ƙungiyar UKCTOCS.Lancet Oncol.2011;12: 38-48.
45. BabjukM, Burger M, CompératEM, Gontero P, MostafidAH,
PalouJ, et al.Ƙungiyar Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararru (TaT1 da Carcinoma A Situ) -
Sabunta 2019.Yuro.2019;76: 639-57.
46. Aragon-Ching JB.Kalubale da ci gaba a cikin ganewar asali, ilmin halitta, da kuma kula da urothelial babba da kuma mafitsara carcinomas.Urol Oncol.2017;35: 462-4.
47. Rizvi S, KhanSA, Hallemeier CL, Kelley RK, Gores GJ.
Cholangiocarcinoma - ra'ayoyi masu tasowa da dabarun warkewa.Nat Rev Clin Oncol.2018;15: 95-111.
48. Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy in hepatocellular
carcinoma: kwayoyin tumor da ke zagayawa da kwayar cutar kwayar cutar DNA.Mol Cancer.2019;18:114.
49. Zhang Y, Yao Y, Xu Y, Li L, Gong Y, Zhang K, et al.Pan-ciwon daji
Gano kwayar cutar DNA da ke yawo a cikin sama da marasa lafiya 10,000 na kasar Sin.Na Komun.2021;12:11 .
50. Eisenhauer EA, Therasse P, BogaertsJ, Schwartz LH, Sargent D, Ford R, et al.Sabbin ka'idodin kimantawa na amsawa a cikin ƙaƙƙarfan ciwace-ciwace: jagororin RECIST da aka sake dubawa (Sigar 1.1).Eur J Cancer.2009;45: 228-47.
51. LitièreS, Collette S, de Vries EG, Seymour L, BogaertsJ.RECIST - koyo daga baya don gina gaba.Nat Rev Clin Oncol.
2017;14: 187-92.
52. Seymour L, BogaertsJ, Perrone A, FordR, Schwartz LH, Mandrekar S, et al.iRECIST: jagororin don ma'aunin amsa don amfani a gwaji
gwajin immunotherapeutics.Lancet Oncol.2017;18: e143-52.
53. PantelK, Alix-Panabières C. Liquid biopsy da ƙananan cututtuka na saura - sababbin ci gaba da abubuwan da ke haifar da magani.Nat Rev Clin Oncol.2019;16: 409-24.
A buga wannan labarin kamar: Qian C, Zou X, Li W, Li Y, Yu W. Mafarin yaƙi da cutar kansa: alamomin cutar kansa kawai.Ciwon daji Biol Med.2023;20: 806-815.
doi: 10.20892/j.issn.2095-3941.2023.0313
Lokacin aikawa: Mayu-07-2024