TS'EKOA MONYANE
Sebaka se khahlano le mofets'e: matšoao a kankere ea bokahohleng feela
Chengchen Qian1, Xiaolong Zou2, Wei Li1,3, Yinshan Li4, Wenqiang Yu5
1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, Chaena;2 Lefapha la Kakaretso ea Karo, Sepetlele sa Pele se Kopanetsoeng sa Univesithi ea Bongaka ea Harbin, Harbin 150001, Chaena;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, Chaena;Sepetlele sa Batho ba 4 sa Setereke se ikemetseng sa Ningxia Hui, Univesithi ea Bongaka ea Ningxia, Yinchuan 750002, Chaena;5Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Laboratory ea RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, Chaena
TS'ELISO
Kankere ke sesosa se ka sehloohong sa lefu lefatšeng ka bophara.Ho lemoha mofetše kapele ho ka fokotsa ho shoa ha mefuta eohle ea mofetše;leha ho le joalo, li-biomarker tse sebetsang tsa ho lemoha kapele li haella bakeng sa mefuta e mengata ea mofets'e.DNA methylation esale e le sepheo se seholo sa thahasello hobane DNA methylation hangata e etsahala pele ho liphetoho tse ling tse bonoang tsa lefutso.Ha ho ntse ho etsoa lipatlisiso ka likarolo tse tloaelehileng tsa mofets'e ho sebelisoa bukana ea tataiso ea tatellano ea maemo bakeng sa DNA methylation, letoto la matšoao a mofetše feela (UCOMs) a hlahile e le likhetho tse matla bakeng sa tlhahlobo e nepahetseng le e nepahetseng ea mofets'e.Le ha boleng ba kliniki ba li-biomarker tsa mofets'e tsa morao-rao bo fokotsehile ke kutlo e tlase le / kapa boits'oaro bo tlase, litšoaneleho tse ikhethang tsa li-UCOM li netefatsa liphetho tse nang le moelelo oa bongaka.Netefatso ea bokhoni ba bongaka ba UCOM ka mofets'e oa matšoafo, molomo oa popelo, endometrial le urothelial e ts'ehetsa ts'ebeliso ea li-UCOM mefuteng e mengata ea mofetše le maemong a fapaneng a bongaka.Ebile, ts'ebeliso ea li-UCOM ha joale e ntse e le tlas'a lipatlisiso tse sebetsang ka tlhahlobo e tsoelang pele mabapi le tlhahlobo ea pele ea mofets'e, tlhahlobo e thusang, katleho ea kalafo, le ho lekola ho khutla hape.Mekhoa ea limolek'hule eo li-UCOM li bonang mofetše ke lihlooho tse latelang tsa bohlokoa tse lokelang ho hlahlojoa.Ts'ebeliso ea li-UCOM maemong a nnete a lefats'e le eona e hloka ts'ebetsong le ntlafatso.
MANTSOE SEHLOOHO
Ho fumanoa ha kankere;ho hlahlojoa ha kankere;DNA methylation;kankere ea epigenetics;li-biomarker tsa kankere
Hobaneng re hloka tse ncha ka potlako li-biomarker?
Ka mor'a ho loantša kankere ka lilemo tse fetang lekholo, kankere e ntse e le tšokelo e bolaeang ka ho fetisisa ea likokoana-hloko molokong oa batho.Kankere e ntse e le taba ea bophelo bo botle ba lefats'e ka linyeoe tse ncha tse limilione tse 19.3 le mafu a ka bang limilione tse 10 a hakanyetsoang ka 20201. Ka 2020 ho ile ha fumanoa linyeoe tse ncha tsa mofets'e tse limilione tse 4.6 naheng ea China, e leng karolo ea 23.7% ea linyeoe tse ncha lefatšeng ka bophara ho latela GLOBOCAN1.Ho feta moo, mafu a ka bang limilione tse 3 a bakiloe ke mofetše naheng ea China ka 2020, e leng 30% ea mafu a amanang le mofetše lefatšeng ka bophara.Lipalo-palo tsena li bonts'itse hore China e maemong a pele ka sekhahla sa liketsahalo le ho shoa ha mofetše.Ho feta moo, tekanyo ea ho phela ha kankere ea lilemo tse 5 ke 40.5%, e leng ka makhetlo a 1.5 ho feta tekanyo ea ho phela ha lilemo tse 5 United States2,3.Palo e tlase haholo ea ho pholoha le ho shoa ha batho Chaena ho feta linaheng tse nang le li-index tse phahameng tsa nts'etsopele ea batho li fana ka maikutlo a hore mokhoa o sebetsang oa ho thibela mofetše le mokhoa oa ho lebela o hlokahala ka potlako.Ho lemoha mofetše kapele ke e 'ngoe ea lintlha tsa bohlokoahali tsamaisong ea bophelo bo botle.Ho lemoha mofetše pele ho nako ho ka ntlafatsa tsoelo-pele le ho phela maemong a pele hoo e batlang e le mefuta eohle ea mofetše4.Mekhoa e atlehileng ea tlhahlobo e lebisitse ho fokotseha ho hoholo ha sekhahla le sekhahla sa lefu la mofetše oa popelo, matsoele, colorectal le tšoelesa ea senya.
Leha ho le joalo, ho fumana mofetše kapele, ha se mosebetsi o bonolo.Ho etsa lipatlisiso ka baeloji le boits'oaro ba mofets'e oa pele, ho hlwaya le ho netefatsa matšoao a ts'eptjoang a ho lemoha kapele, le ho nts'etsapele mahlale a fihlellehang le a nepahetseng a ho lemoha esale pele esale e le litšitiso tse kholo ts'ebetsong4.Ho lemoha ka nepo mofetše ho ka khetholla ho se be kotsi ho tsoa ho maqeba a kotsi, e thusang ho qoba lits'ebetso tse sa hlokahaleng le ho nolofatsa taolo e eketsehileng ea mafu.Mekhoa ea hona joale ea ho lemoha kapele e kenyelletsa li-biopsies tse thehiloeng ho endoscope, litšoantšo tsa bongaka, cytology, immunoassays, le liteko tsa biomarker5-7.Kaha lia ferekanngoa ebile li bitsa chelete e ngata, li-biopsies tse thehiloeng ho endoscope li jara moroalo o boima ka tlhaho e le mokhoa o moholo oa bongaka o itšetlehileng ka basebetsi ba litsebi.Joalo ka cytology, mekhoa e 'meli ea tlhahlobo e itšetlehile ka litsebi tsa bongaka mme e ipapisitse le kahlolo ea motho ka ts'ebetso e hole haholo8.Ka lehlakoreng le leng, litlhahlobo tsa immunoassay ha li nepahale haholo, ha ho nahanoa ka litekanyetso tse phahameng tsa bohata.Litšoantšo tsa bongaka, joalo ka leqheka la ho hlahloba, li hloka lisebelisoa tse theko e boima le litsebi tse khethehileng.Kahoo, litšoantšo tsa bongaka li fokola haholo ka lebaka la ho fumaneha habonolo.Bakeng sa mabaka ana kaofela, li-biomarker li bonahala e le khetho e ntle bakeng sa ho lemoha mofetše kapele.
Ngollano le: Yinshan Li le Wenqiang Yu
Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn
ORCID ID: https://orcid.org/0009-0005-3340-6802 le
https://orcid.org/0000-0001-9920-1133
E amohetse Phato 22, 2023;e amohetse Mphalane 12, 2023;
e phatlalalitsoe inthaneteng ka la 28 Pulungoana 2023.
E fumaneha ho www.cancerbiomed.org
©2023 Cancer Biology & Medicine.Creative Commons
Attribution-NonCommerce License ea Machaba ea 4.0
Li-biomarker hajoale li arotsoe e le liprotheine, matšoao a phetoho ea DNA, matšoao a epigenetic, ho se tloaelehe ha chromosomal, matšoao a RNA a nkiloeng ka kotloloho ho tsoa lihlahala, kapa likhechana tsa hlahala tse fumanoeng ka tsela e sa tobang marong a 'mele.Matšoao a protheine ke li-biomarker tse sebelisoang haholo tlhahlobong le tlhahlobong ea mofetše.Li-protein biomarker, e le li-biomarker tse hlahlobang, li lekanyelitsoe ke tšekamelo ea ho angoa ke liso tse kotsi, tse lebisang ho hlahlobisiseng le ho phekoloa ka ho feteletseng, joalokaha ho tlalehiloe ka α-fetoprotein le prostate-specific antigen (PSA)9,10.Matšoao a RNA a kenyelletsa mekhoa ea ho hlahisa liphatsa tsa lefutso le matšoao a mang a RNA a sa ngolisoeng. Motsoako oa liphatsa tsa lefutso tsa RNA li ka bonoa ho sebelisoa lisampole tsa moroto, kutloisiso ea eona e neng e le hole le ho khotsofala (60%) bakeng sa lihlahala tsa mantlha, le ho fumanoa ha tsona angoa ke tšenyeho e bonolo ea RNA tikolohong e tloaelehileng11.Matšoao a liphatsa tsa lefutso le epigenetic ka bobeli a tobane le bothata ba ho ata ha lihlahala le meeli ea mefuta ea mofetše.
DNA methylation e 'nile ea e-ba mokhethoa ea matla e le moemeli oa pele oa ho lemoha mofets'e ho tloha ha a qala ho amahanngoa le mofets'e ke Feinberg ka 198312. DNA methylation aberrations e hlokomeloa ka mekhahlelo eohle ea mofets'e, pele ho nako ea precancerous.Aberrant DNA hypermethylation hangata e etsahala lihlekehlekeng tsa CpG ho bahlahisi ba liphatsa tsa lefutso ho loantša li-tumor suppressors13,14.Liphuputso li boetse li bontšitse hore DNA hypermethylation e sa tloaelehang e kenya letsoho taolong ea li-regulator tsa nts'etsopele15.Phula ea DNA methylation, e atisang ho amahanngoa le batsamaisi ba nts'etsopele le kankere ea hypermethylated, e ka 'na ea fetola mokhoa oa ho hlahisa liphatsa tsa lefutso ho mokhoa o tsitsitseng oa DNA methylation-e itšetlehileng ka eona le ho fokotsa khokahanyo ho methylated histone H3K27me3 le liprotheine tse amanang le polycomb16,17.
Har'a palo e kholo ea li-marker tsa DNA methylation tse hatisitsoeng, tse 'maloa li atlehile ho qala 'marakeng;Leha ho le joalo, li-marker tsa morao-rao tsa DNA methylation le liphanele tsa tlhahlobo ha li e-s'o bule ka botlalo monyetla oa ho lemoha mofetše kapele ka mabaka a mangata18.Leha boholo ba bona bo bonts'a ts'ebetso e amohelehang ho sebelisoa tlhaiso-leseling ea polokelo, li-biomarker tsena hangata ha li sebetse hantle lefatšeng la 'nete ka lebaka la hore lisampole tsa lefats'e la nnete hangata li rarahane ebile ha li emele joalo ka tse khethiloeng litsing tsa polokelo ea litaba.Ho fumanoa ha methylation ea mofets'e oa mofets'e o latelang ho bonts'itsoe hore o na le maikutlo a 16.8% le 40.4% mokhahlelong oa I le oa II, ka ho latellana19.Liteko tsa ho lemoha kapele li hloka botsitso bo boholo le li-biomarker tse nepahetseng haholoanyane.
Ho sibolloa ha mofetše oa Universal feela (UCOM) ho sebelisa tatellano ea boemo ba tataiso (GPS)
Ho sa tsotellehe lilemo tse mashome tsa lipatlisiso tsa kankere, thibelo le phekolo e khotsofatsang ha e e-s'o fihleloe.Ho hlokahala mekhoa e mecha ho thusa bafuputsi ho hlahloba mofetše ka botlalo.Lilemong tse 23 tse fetileng, matšoao a 6 a mofetše, joalo ka ho qoba apoptosis, tlhaselo ea lisele le metastasis, joalo-joalo, a eketsehile ho fihla ho 14 ka ho kenyelletsa likarolo tse kang nonmutational epigenetic reprogramming le polymorphic microbiomes20,21.Ha lintlha tse ling tse amanang le mofets'e li ntse li senoloa, maikutlo a eketsehileng a hlahisoa lipatlisisong tsa mofetše.Patlisiso ea mofets'e e se e fetohile e ncha butle-butle ka litsela tse peli (tloaelo le botho).Ka nts'etsopele ea oncology e nepahetseng lilemong tsa morao tjena, sepheo sa lipatlisiso tsa mofets'e se itšetlehile ka kalafo e lebisitsoeng ho motho ka mong le ho fapana ha mofets'e22.Kahoo, li-biomarker tsa mofets'e tse sa tsoa fumanoa li tsepamisitse maikutlo haholo mefuteng e itseng ea mofetše, joalo ka PAX6 forcervical cancer23 le BMP3 bakeng sa colorectal cancer24.Ts'ebetso ea li-biomarker tsena tse ikhethileng mefuteng ea mofets'e ea fapana, empa ho ntse ho sa khonehe hore batho ba kotsing ea ho etsa tlhahlobo ea mofetše ka nako e le 'ngoe ka lebaka la khaello ea ho fumana sampole ea tlhaho le litšenyehelo tse phahameng.E ka ba hantle ha re ka tsebahatsa "biomarker" e le 'ngoe e matla e sebetsang bakeng sa mefuta eohle ea mofetše haufinyane.
Ho fihlela sepheo se setle joalo, ho tlameha ho khethoa mokhethoa ea betere oa biomarker lethathamong la mefuta e ka bang teng ea biomarker.DNA methylation aberrations, har'a litlaleho tsohle tsa lefutso le epigenetic, li tsejoa li amana le mofetše 'me ke tse ling tsa pele, haeba e se tsa pele, tse sa tloaelehang tse amanang le mofetše ho etsahala ka tatellano ea liketsahalo.Patlisiso ea DNA methylation e qalile kapele, empa e sitisitsoe ke khaello ea mekhoa ea lipatlisiso.Har'a libaka tse limilione tse 28 tse ka bang teng tsa methylated CpG ho genome, palo e laolehang e tlameha ho bonoa le ho hokahanngoa le genome ho utloisisa tumorigenesis hamolemo.Whole genome bisulfite sequencing (WGBS), e nkoang e le tekanyetso ea khauta ea DNA methylation sequencing, e ka koahela feela 50% ea Cs liseleng tsa mofetše ka lebaka la mofuta oa kalafo ea bisulfite e pshatlang likhechana tsa DNA le ho theola ho rarahana ha liphatsa tsa lefutso nakong. phetoho ea Cs-to-Ts25.Mekhoa e meng, joalo ka 450k chips, e koahela feela 1.6% ea genome methylation.Ho ipapisitsoe le data ea 450k, DNA methylation detection panel e na le 35.4% sensitivity bakeng sa mefuta e 6 ea mofets'e oa sethala sa I26.Mefokolo ea mefuta ea mofetše, ts'ebetso e mpe, le lerata le hlahisoang ke mekhoa ea ho lemoha ts'ebetsong ea tlhahlobo e fetohile litšitiso tse kholo bakeng sa liphanele tsa ho lemoha mofetše.
Ho batlisisa hamolemo mekhoa ea epigenetic ea lisele nakong ea tumorigenesis le metastasis, re thehile GPS e ikhethang bakeng sa tlhahlobo ea genome-wide DNA methylation, e koahelang ho fihla ho 96% ea libaka tsa CpG ho 0.4 limilione tse likete tse 25.GPS ke mokhoa oa tatellano oa tatellano o sebelisang karolo ea 3 ′ ea sekhechana sa DNA ea methyl-cytosine e sa fetoheng kamora kalafo ea bisulfite e tataisang ho lokisoa ha DNA methylation calculation ea pheletso ea 5 ka tatellano ea li-pair-end (Setšoantšo sa 1)25.Khoele e tataisang ea methyl-cytosine, e sebetsang e le khoele ea template, e thusa ho hokahanya sebaka se phahameng sa GC se khutlisetsang datha e lahliloeng ka ho fetesisa ho WGBS ea setso.Karolo e phahameng ea GPS e fana ka tlhaiso-leseling e ngata haholo ea DNA methylation, e re lumellang ho hlahloba lintlha tsa mofetše tsa methylation ka qeto e phahameng haholo libakeng tseo pele ho neng ho sa etsoa lipatlisiso.
GPS e re fa sesebelisoa se matla sa ho batlisisa homogeneity ea mofets'e, e ka nolofatsang lipatlisiso tsa mofets'e haholo le ho fumana tlhaloso e akaretsang ea tum- genesis le metastasis.Ha ho ntse ho hlahlojoa lintlha tsa GPS tsa lisele tsa mofetše, ho ne ho etsahala ntho e ikhethang khafetsa.Ho na le libaka tse 'maloa tse neng li bonahala li na le hypermethylated ka mokhoa o sa tloaelehang mefuteng e mengata ea lisampole tsa mofetše.Sephetho sena se neng se sa lebelloa hamorao se ile sa netefatsoa hore se sebetse joalo ka li-UCOM.Ho hlahlobiloe lisampole tse fetang 7,000 tse tsoang mefuteng e 17 ea mofets'e sebakeng sa database sa The Cancer Genome Atlas (TCGA), moo re khethileng UCOM ea pele, HIST1H4F, mofuta o amanang le histone o nang le hypermethylated mefuteng eohle ea mofets'e27.Ka mor'a moo ho ile ha fumanoa letoto la li-UCOM 'me tsa netefatsoa polokelong ea TCGA, database ea Gene Expression Omnibus (GEO), le lisampole tsa kliniki tsa lefats'e la nnete.Ho tloha hajoale, HIST1H4F, PCDHGB7, le SIX6 li se li fumanoe 'me li netefalitsoe e le li-UCOM.Ho sibolloa ho sa lebelloang ha li-UCOM ho fana ka karabo e matla tlhokahalong ea ho lemoha mofetše kapele.Li-UCOM li fana ka tharollo bakeng sa ho fumana letšoao le le leng la mofets'e o mongata.
Litšobotsi tsa UCOM
Ha ho netefatsoa, li-UCOM li bonts'itsoe ho bonts'a litšobotsi tse 'ne tse kholo tse nolofalletsang li-UCOM ho feta matla a li-biomarker tsa hajoale (Setšoantšo sa 2).
E ikgethang ho bokgopo
Li-UCOM li ikhetha ka liso tsa mofetše kapa tsa pele ho mofetše 'me ha li amehe ke liphetoho tse tloaelehileng tsa physiologic.A mang a matšoao a hajoale a amanang le mofets'e a sebelisitsoeng haholo tlhahlobong ea pele le/kapa tlhahlobo a lebisitse ho hlahlobisiso e feteletseng.Maemo a phahameng a PSA, sesebelisoa sa tlhahlobo se ngolisitsoeng ka molao, se boetse se bonoa maemong a bobebe, joalo ka prostate hyperplasia le prostatitis10.Ho hlahlojoa ho feteletseng le ho phekoloa ho feteletseng ho lebisang ho fokotsehileng bophelo ba bophelo ka lebaka la mala, moroto le mathata a thobalano28.Li-biomarker tse ling tse thehiloeng ho protheine le tse sebelisoang haholo maemong a kliniki, joalo ka CA-125, ha lia fana ka melemo e mengata ha li ntse li baka tlhahlobo e feteletseng le kalafo e feteletseng29.Bophahamo bo phahameng ba li-UCOM bakeng sa bofokoli bo qoba mefokolo ena.UCOM, PCDHGB7, e khetholla ka katleho liso tse phahameng tsa squamous intraepithelial (HSILs) le mofets'e oa popelo ho tsoa ho lisampole tse tloaelehileng le lisosa tse tlase tsa squamous intraepithelial (LSILs), athe boholo ba li-biomarker tse ling li ka khetholla feela mofetše oa popelo ho lisampole tse tloaelehileng30.Le hoja PCDHGB7 e sa bone phapang e khōlō pakeng tsa endometrium e tloaelehileng le endometrial hyperplasia, ho na le phapang e khōlō pakeng tsa endometrium e tloaelehileng le hyperplasia e sa tloaelehang, 'me ho na le phapang e kholo pakeng tsa endometrium e tloaelehileng le kankere ea endometrial (EC) e thehiloeng ho PCDHGB731.Li-UCOM li ikhethile ka lebaka la liso tse mpe tse fumanehang ho database le lisampole tsa bongaka.Ho ea ka pono ea mokuli, li-UCOM tse ikhethang li fokotsa moeli oa ho utloisisa matšoao a fapaneng a sa sebetseng hantle a sa sebetseng hantle le matšoenyeho a ts'oanang nakong ea tlhahlobo.Ho ea ka pono ea lingaka, li-UCOM tse ikhethang li khetholla mafu a kotsi ho tsoa ho maqeba a kotsi, a thusang ho hlahloba bakuli le ho fokotsa mekhoa ea bongaka e sa hlokahaleng le phekolo e feteletseng.Ka hona, li-UCOM tse ikhethang li fokotsa ho fokotsoa ha tsamaiso ea bongaka, li imolla khatello ea kelello, 'me li etsa hore ho be le lisebelisoa tse eketsehileng tsa bongaka ho ba hlokang.
Setšoantšo sa 1 Schematic of GPS workflow for DNA methylation discovery25.Mola o moputsoa: tatellano ea DNA ea ho kenya;mola o mofubelu: DNA e tšoaroang ka T4 DNA polymerase, ho nkela cytosine sebaka ka 5'-methylcytosine qetellong ea 3' ea ho kenya letsoho;blue C with Me: methylated cytosine;blue C: unmethylated cytosine;mosehla T: thymine25.
Tsohle kapa ha ho letho
Li-UCOM li fumaneha feela liseleng tsa mofetše 'me li fumanoa li tiile hoo e batlang e le liseleng tsohle tsa mofetše.HIST1H4F e netefalitsoe ho ba hypermethylated hoo e batlang e le mefuta eohle ea hlahala empa eseng ka lisampole tse tloaelehileng27.Ka mokhoa o ts'oanang, PCDHGB7 le SIX6 le tsona li bontšitsoe hore li na le hypermethylated ka lisampole tsohle tsa tumor empa eseng ka lisampole tse tloaelehileng30-32.Tšobotsi ena e ikhethang e ntlafatsa haholo ts'ebetso ea li-UCOM mabapi le moeli oa ho lemoha le kutloisiso.Hoo e ka bang 2% ea lisele tsa mofetše li ka aroloa ka lisampole, e leng se etsang hore li-UCOM e be li-biomarker tse hlokolosi haholo ho feta li-biomarker tse ngata tse teng30. Joalo ka biomarker e sebelisetsoang ho lemoha mofetše oa colorectal, liphetoho tsa KRAS li teng hoo e ka bang 36% ea linyeoe tsa mofetše oa mala. ho fana ka maikutlo a matla a fokolang a tlhahlobo33.Ho ata ho tlase ha liphetoho tsa KRAS ho mofetše oa colorectal ho fokotsa KRAS hammoho le li-biomarker tse ling.Ebile, motsoako oa li-biomarker o kanna oa bonahala o ts'episa qalong, empa ha se kamehla o hlahisang sephetho se khotsofatsang ha o ntse o bonts'a lerata le leholo haholo tlhahlobong ea tlhahlobo mme hangata o kenyelletsa mekhoa e rarahaneng ea liteko.Ka lehlakoreng le leng, PCDHGB7 le li-UCOM tse ling li teng mefuteng eohle ea mofetše.Li-UCOM li lemoha likarolo tse nang le mofetše mefuteng e fapaneng ea lisampole tsa mofets'e ka mokhoa o nepahetseng haholo ha li ntse li felisa lits'ebetso tse rarahaneng tsa tlhahlobo ea ho hlakola lerata.Ha ho thata ho bona mofets'e ka sampole e ngata, empa ho thata haholo ho bona mofetše ka sampole e nyane.Li-UCOM li khona ho bona palo e nyane ea mofetše.
Setšoantšo sa 2 Litšobotsi tsa UCOM.
Ho fumanoa ha mofets'e pele ho liphetoho tsa pathological
Li-UCOM li ka bonoa sethaleng sa pele ho mofetše pele ho liphetoho tsa pathological.Joaloka li-biomarker tsa epigenetic, lintho tse sa tloaelehang tsa UCOM li etsahala nakong ea pele ho feta tse sa tloaelehang tsa phenotypic 'me li ka bonoa ho pholletsa le tumorigenesis, tsoelo-pele, le metastasis34,35.Kutloelo-bohloko ea UCOM ha nako e ntse e feta e ntlafatsa ts'ebetso ea UCOM ho lemoha mofetše oa pele le liso tsa pele ho mofetše.Ho lemoha mofetše oa pele o thehiloeng ho li-biopsies le cytology ho ka ba thata ho esita le litsebi tsa mafu a nang le phihlelo.Biopsy e le 'ngoe e fumanoeng ka colposcopy e tlalehiloe e le ntle ho 60.6% ea lisampole tsa HSIL+.Li-biopsies tse eketsehileng lia hlokahala bakeng sa liso tse ngata ho eketsa kutlo36.Ka lehlakoreng le leng, UCOM, PCDHGB7, e na le kutlo ea 82% bakeng sa lisampole tsa HSIL+, e fetang kutloisiso ea li-biopsies le li-biomarker tse ngata30.Letšoao la methylation, FAM19A4, le na le kutloisiso ea 69% bakeng sa CIN2 +, e tšoanang le cytology, empa e ke ke ea khetholla CIN1 ho tloha lisampole tse tloaelehileng37.Li-UCOM li bontšitsoe e le "biomarker" e hlokolosi haholoanyane ea ho lemoha kapele.Ha ho bapisoa le lingaka tse ipapisitseng le boiphihlelo, li-UCOM li na le kutlo e phahameng ea ho lemoha bakeng sa mofets'e oa methati ea pele, e leng eona e tlatsetsang ho ntlafatseng prognoza ea mofets'e le ho phela30.Ho feta moo, li-UCOM li fana ka sethala sa ho lemoha se fumanehang libakeng tse se nang litsebi tse nang le boiphihlelo 'me se ntlafatsa haholo ts'ebetso ea ho lemoha.Ka mekhoa e ts'oanang ea lisampole le mekhoa ea ho lemoha, ho fumanoa ha UCOM ho fana ka liphetho tse tsitsitseng le tse bonolo ho toloka tse lumellanang hantle le protocol ea tlhahlobo e hlokang basebetsi ba fokolang ba litsebi le lisebelisoa tsa bongaka.
Ho bonolo ho lemoha
Mekhoa ea hajoale ea ho lemoha methylation ea DNA e rarahane ebile e nka nako.Boholo ba mekhoa e hloka phetoho ea bisulfite, e bakang tahlehelo ea boleng ba sampuli mme mohlomong e hlahisa liphello tse sa tsitsang le tse sa nepahalang.Ho fokola ha ho ikatisa ho bakoang ke phekolo ea bisulfite ho ka 'na ha lebisa pherekano ho lingaka le bakuli le ho kena-kenana le ho feta le mekhoa ea ho latela le / kapa ea phekolo.Ka hona, re ile ra boela ra fetola mokhoa oa ho lemoha UCOM ho qoba kalafo e nang le bothata ea bisulfite ea lisampole, ho amohela litlhoko tsa kopo ea tleliniki, le ho ntlafatsa phihlello.Re thehile mokhoa o mocha oa ho sebelisa li-enzyme tsa thibelo ea methylation tse kopantsoeng le PCR (Me-qPCR) ea nako ea nnete ea fluorescent ho lekanya boemo ba methylation ba UCOM nakong ea 3 h ho sebelisa mekhoa e bonolo ea ho sebetsana le eona (Setšoantšo sa 3).Me-qPCR e ka amohela mefuta e mengata ea lisampole, joalo ka pokello ea mafu a 'mele le lisampole tsa moroto tse iketselitseng.Lisampole tse bokelletsoeng tsa kliniki li ka sebetsoa, tsa bolokoa, 'me tsa tsoela pele habonolo ho fumanoa ho sebelisoa mokhoa o tloaelehileng oa ho ntša DNA.DNA e nkiloeng e ka sebelisoa ka ho toba sethaleng sa Me-qPCR bakeng sa karabelo ea pitsa e le 'ngoe le liphello tsa palo ea lihlahisoa.Kamora tlhahlobo e bonolo ea sephetho ho sebelisa mefuta ea tlhahlobo e kentsoeng le ho netefatsoa ho mefuta e itseng ea mofets'e, qeto ea ho qetela ea liphetho tsa tlhahlobo ea UCOM e hlalosoa mme e hlahisoa e le boleng ba halofo ea palo.Sethala sa Me-qPCR se feta mokhoa o tloaelehileng oa bisulfite-pyrosequencing ho UCOM ha o ntse o boloka 3 h ea phetoho ea bisulfite, ho latela protocol ea EZ DNA Methylation-Gold kit.Sethala sa boqapi sa methylation se etsa hore tlhahlobo ea UCOM e tsitse, e nepahale haholoanyane, 'me e fihlellehe haholoanyane30.
Setšoantšo sa 3 Ts'ebetso ea ho fumana li-UCOM.Mefuta ea lisampole e kenyelletsa BALF e entsoeng ka profeshenale, borashe ba Pap, le/kapa moroto o ipokeletseng.Ts'ebetso ea ho ntša DNA e ka amoheloa ho mochine o ikemetseng, oo sehlahisoa sa oona se ka fumanoang ka ho toba ke qPCR.
Tšebeliso ea li-UCOM
Kankere ea matšoafo
Kankere ea matšoafo ke kankere ea bobeli e fumanoang hangata le e bolaeang ka ho fetisisa lefatšeng ka bophara, e ikarabellang bakeng sa 11.4% ea linyeoe tse ncha le 18.0% ea mafu a macha.Har'a litlhahlobo tsohle, 85% ke mofets'e o seng o monyane oa lisele tsa matšoafo (NSCLC) mme 15% ke mofetše o monyane oa lisele tsa matšoafo (SCLC), o nang le boemo bo phahameng ba malignancy38.Ho hlahlojoa ha tekanyo e tlaase ea computed tomography (LDCT) ke mokhoa o khothalletsoang hajoale oa ho hlahloba mofetše oa matšoafo 'me o bontšitsoe ho ntlafatsa ho lemoha kapele le ho fokotsa lefu6;leha ho le joalo, ka lebaka la maemo a tlase le phihlello e fokolang, LDCT ha e so sebetse joalo ka mokhoa o khotsofatsang oa tlhahlobo, joalo ka matšoao a mang a tloaelehileng a mofetše, joalo ka CEA39.Litšenyehelo le monyetla oa ho hlahlojoa le ho hlahlojoa hampe ha leano la tlhahlobo ea LDCT li sitisa tsoelopele ea tlhahlobo ea mofetše oa matšoafo40.HIST1H4F, UCOM, e na le monyetla o moholo oa ho tsebahatsa li-biomarker tsa pele ho lisampole tsa bronchoalveolar fluid (BALF)27.HIST1H4F e na le hypermethylated ka har'a lung adenocarcinoma le lung squamous cell carcinoma, e nang le boitsebiso bo khethehileng ba 96.7% le kutloisiso ea 87.0% (Setšoantšo sa 4A), le ts'ebetso e ikhethang bakeng sa mofets'e oa mohato oa I27.HIST1H4F e na le lintlha tse ikhethang tsa 96.5% le kutloisiso ea 85.4% bakeng sa NSCLC, le 96.5% le 95.7%, ka ho latellana, bakeng sa SCLC27.Ho feta moo, lisampole tsa mefuta e meng e robeli ea mofets'e, ho kenyeletsoa mofets'e oa pancreatic le colorectal, li netefalitse hore HIST1H4F ke hypermethylated mefuteng eohle e robeli27.
Kankere ea popelo
Kankere ea molomo oa popelo e bile sesosa sa bone sa lefu la mofetše ho basali ka 2020, e bakileng 3.1% ea linyeoe tse ncha le 3.4% ea mafu a amanang le mofetše lefatšeng ka bophara.Ho felisa mofetše oa molomo oa popelo ka 2030, joalo ka ha ho sisintsoe ke WHO, ho fumanoa pele mofetše oa popelo ke ntho e hlokahalang.Haeba e fumanoa qalong, sekhahla sa ho phela sa lilemo tse 5 se fihla ho 92% ka mofetše oa popelo o hlaselang41.Litaelo tsa Mokhatlo oa Kankere oa Amerika (ACS) li fana ka maikutlo a liteko tsa cytology ea cervical, liteko tsa mantlha tsa HPV, kapa liteko tsa tlhahlobo42.Cytology ea cervical e hlasela 'me e ka lemoha feela 63.5% ea CIN2+ case37.
PCDHGB7, ka lehlakoreng le leng, e sebelitse betere haholo ka ho sebelisa Pap smear le ho tsoa ka botšehaling, 'me e ka khona ho khetholla hantle HSIL ho LSIL nakong ea pele-pele.PCDHGB7 feela e na le kutloisiso ea 100.0% le e khethehileng ea 88.7% bakeng sa mofetše oa popelo (Setšoantšo sa 4B), le kutloisiso ea 82.1% le 88.7% e khethehileng bakeng sa lisampole tsa HSIL+30.PCDHGB7 e boetse e na le kutlo ea 90.9% le 90.4% e ikhethang lisampoleng tsa botšehali bakeng sa mofetše oa molomo oa popelo, tseo ho leng bonolo ho li bokella30.Ha e kopantsoe le teko e phahameng ea kotsi (hr) HPV kapa Thinprep Cytology Test (TCT), PCDHGB7 e na le kutloisiso e eketsehileng ea 95.7% le e khethehileng ea 96.2%, e fetang haholo ea tlhahlobo ea hrHPV (20.3%), TCT (51.2% ), 'me tse peli li kopantsoe (57.8%) bakeng sa mofetše oa popelo30.PCDHGB7 e boetse e bontšitsoe hore e na le hypermethylated mefuteng ea 17 ea kankere ho tloha ho database ea TCGA, e bontšang ho tšoaneleha ha eona ho UCOM family30.
Setšoantšo sa 4 UCOMs se netefalitsoe mefuteng e mene ea mofetše lithutong tse kholo tsa bongaka.A. Ts'ebetso ea HIST1H4F, UCOM, ho lemoha kankere ea matšoafo ea 508 sampuli.B. Ts'ebetso ea PCDHGB7, UCOM, ho lemoha mofetše oa mokokotlo oa li-sampuli tsa 844.C. Ts'ebetso ea PCDHGB7, UCOM, ho lemoha kankere ea endometrial ea 577 endometrial Pap le Tao brush samples.D. Ts'ebetso ea SIX6, UCOM, ho lemoha kankere ea urothelial ea 177 sampuli.
EC
EC ke e 'ngoe ea mefuta e atileng haholo ea mofets'e oa tsamaiso ea ho ba le bana lefatšeng ka bophara, 'me ho hakanngoa hore ho na le batho ba bacha ba limilione tse 4.2 le 1% ea mafu a bakoang ke mofets'e selemo le selemo.Ka tlhahlobo e atlehileng ea tlhahlobo haufinyane, EC ea phekoleha 'me e na le sekhahla sa ho phela sa lilemo tse 5 sa 95% bakeng sa mofetše oa Mokhahlelo oa I.Bakuli ba nang le matšoao, joalo ka ho tsoa mali ka mokhoa o sa tloaelehang oa popelo, ba fumana tlhahlobo ea bongaka ea nako le nako 'me ba etsoa mekhoa e hlaselang le e bohloko ea biopsy, ho sa tsotellehe hore ke 5% -10% feela e qetellang e hlahisa EC43.Transvaginal ultra-sound, e le mokhoa o tloaelehileng oa ho lemoha, ha o tšepahale haholo ka lebaka la ho se khone ho khetholla ho tsoa ho liphetoho tse mpe tsa endometrical le tekanyo e phahameng ea bohata-e ntle44.
Papiso e ts'oanang ea serum CA-125, e leng EC biomarker e sebelisitsoeng hohle, le PCDHGB7.Serum CA-125 e ne e na le kutloisiso ea 24.8%, e fanang ka maikutlo a hore CA-125 ke letšoao le sa lekaneng bakeng sa EC ho sa tsotellehe ho khetheha ha 92.3%31.Ho fumanoa ha PCDHGB7 ho sebelisa lisampole tsa Pap brush ho hlahisitse kutlo ea 80.65% le ho khetheha ea 82.81% bakeng sa mekhahlelo ea ECatall, ha borashe ba Tao bo ne bo e-na le kutlo ea 61.29% le ho khetheha ha 95.31% 31.PCDHGB7 ea tlhahlobo ea tlhahlobo, e thehiloeng ho Me-qPCR, e fane ka kutloisiso ea 98.61%, e khethehileng ea 60.5%, le ho nepahala ka kakaretso ea 85.5%, ho sebelisa Pap le Tao brush samples (Figure 4C)31.
Kankere ea urothelial
Kankere ea urothelial, e nang le senya, renal pelvis, le mofets'e oa ureter, e bile mofetše oa bosupa o fumanoeng khafetsa ka 2020 lefatšeng ka bophara, o bakile 5.2% ea linyeoe tse ncha le 3.9% ea mafu1.Lik'hemik'hale tsa Urothelial, tse fetang 50% ea tsona ke mofetše oa senya, e ne e le mofetše oa bone o fumanoeng khafetsa United States ka 2022, e leng karolo ea 11.6% ea linyeoe tse sa tsoa fumanoa tse3.Hoo e ka bang karolo ea 75 lekholong ea kankere ea senya e khetholloa e le kankere ea senya e sa amaneng le mesifa e lekanyelitsoeng feela mucosa kapa submucosa45.cystoscopy biopsy ke tekanyetso ea khauta ea ho hlahloba mofetše oa urothelial o kentsoeng ke fluorescence in situ hybridization (FISH) le liteko tsa cytology.LIHLAPI le cytology li na le ts'ebetso e mpe ea ho hlahloba, 'me cystoscopy e ts'oarella ebile e na le kotsi e ka sehloohong ea ho lahleheloa ke li-microlesion, ho hlalosa liso ka tsela e fosahetseng,' me e ka 'nang ea baka ho ata kapa ho khutlela mokhoeng oa kankere46.UCOM e netefalitsoeng, PCDHGB7, e boetse e bonts'itsoe e le hypermethylated ka mofetše oa urothelial, e nang le sebaka se ka tlase ho 0.86, e fanang ka maikutlo a hore ho na le bokhoni ba ho hlahloba30.Ho tsoela pele ho netefatsa li-UCOM tse ngata le ho amohela mefuta e mengata ea sampole, SIX6, buka e ncha ea UCOM, e ile ea hlahlojoa 'me ea bonts'a bokhoni bo botle ba tlhahlobo ea tlhahlobo ea pele ea mofetše oa urothelial o sebelisa lisampole tsa moroto sethaleng sa Me-qPCR.Ho fumanwa ha SIX6 ho sebedisa disampole tsa moroto ho bontshitse kutlwisiso ya tlhodisano ya 86.7% le makgetheng a 90.8% (Setshwantsho sa 4D), ha e sa hlaselehe mme ho le bonolo ho e fumana32.Monyetla oa SIX6 oa tlhahlobo ea metastasis le tlhahlobo ea katleho ea kalafo hajoale o ntse o etsoa lipatlisiso.
Bokamoso le mathata
Li-UCOM li na le ts'ebetso e matla molemong oa tlhahlobo ea mafu a mangata a mofetše, empa ho na le mosebetsi o mongata o lokelang ho etsoa.Re ntse re atolosa lenane la li-UCOM mme re ntse re netefatsa li-UCOM mefuteng e mengata ea mofetše, ho kenyelletsa le tseo ka tloaelo ho leng thata ho li lemoha.Liphetho tsa netefatso ho tsoa litsing tsa polokelo tsa TCGA li netefalitse ts'ebeliso ea li-UCOM mefuteng e mengata ea mofetše le maemong a mangata.Phuputsong ea pele, li-UCOM li bontšitsoe hore li na le bokhoni bo matla ba ho hlahloba li-cholangiocarcinomas le pancreatic adenocarcinomas, tseo hoo e batlang e le ho ke keng ha khoneha ho li hlahloba ka nako e khutšoanyane ka mekhoa ea hona joale ea ho hlahloba32,47.Bokhoni ba ho bona mofets'e o sa tloaelehang ka li-UCOM bo ka sebelisoa ka tumor e potolohang ea DNA (ctDNA) ke sethala se ntlafalitsoeng sa biopsy sa mokelikeli48.Boithuto bo amanang le phanele ea ho lemoha mofetše oa plasma ea DNA e hlahisitse kutloisiso ea 57.9%49.Ho sa tsotellehe maemo a phahameng, ts'ebetso e akaretsang e senola hore ho ntse ho e-na le sebaka sa ntlafatso.
Litšobotsi tse ikhethang tsa li-UCOM li boetse li tšehetse lipatlisiso tsa bokhoni ba UCOM tlhahlobong ea katleho ea kalafo le ho lekola khafetsa.Ho ea ka Mekhahlelo ea Tlhahlobo ea Likarabo ho Lihlahala Tse Tiileng (RECIST), ho nahana ka bongaka ke mokhoa o khothaletsoang bakeng sa ho lekola khafetsa le ho hlahloba katleho ea kalafo, ha matšoao a tumor a sebelisoa a le mong bakeng sa tlhahlobo50.Ha e le hantle, leha ho le joalo, mekhoa ea litšoantšo e angoa haholo ke khafetsa le nako, 'me ka hona e pepesetsa bakuli kotsing le litšenyehelo tse phahameng51,52.SIX6 e netefalitsoe hore e sebetse e le selelekela sa metastasis ea mofetše oa matsoele32.Tlhokomelo ea ctDNA e thehiloeng ho Liquid biopsy e thusa ho beha leihlo ka nako ea 'nete ho feta likhoeli tse fokolang tse setseng pele ho tlhahlobo ea radiologic, ka nepo e liehang le ho thibela tsoelo-pele e amanang le mofetše53.Liphetho tsa pele li fana ka maikutlo a hore UCOM e bonts'a boemo ba hypermethylation ea mofets'e ka nako ea nnete hang kamora ho buuoa le kalafo32.Boikutlo bo phahameng bo bonts'itsoeng ke li-UCOM le ho sebetsa mefuteng e mengata ea lisampole tse sa tsitsang li lumella li-UCOM ho sebetsa e le mokhoa o nepahetseng oa ho lekola li-biomarker ha li ntse li boloka melao e phahameng ea bakuli.
Ka nako e ts'oanang, phihlello ea sechaba tekong ke taba e 'ngoe e kholo e hlokang boiteko bo eketsehileng.Le hoja litšebelisano tsa ho lemoha UCOM li amohetsoe lipetleleng tse ngata ka tšepo ea ho thusa bakuli ba bangata, ho hlahlojoa le ho hlahlojoa ha pro bono ho 'nile ha etsoa ka mafolofolo mahaeng a Chaena.Li-UCOM li hloka phihlello e ntlafalitsoeng hore li tšoanelehe ho ba sesebelisoa se ka khonehang sa tlhahlobo, haholo-holo libakeng tse sa tsoelang pele.
Le ha ts'ebeliso ea UCOM e etsa hore ho fumanoe kapele ho ts'episa, tse ngata tse sa tsejoeng ka UCOM li teng.Ka boithuto bo matla, lipatlisiso tse ling li netefalitsoe mabapi le hore na ke hobaneng ha li-UCOM li le teng ka har'a mofetše.Mekhoa ea taolo ea epigenetic e ka tlase ho UCOM e lokeloa ke lipatlisiso tse ling, e ka lokafatsang tataiso e ncha bakeng sa kalafo ea mofets'e.Ha re khutlela puisanong pakeng tsa tumor homogeneity le heterogeneity, re thahasella hore na ke hobane'ng ha UCOM e ka ba mokhelo ho bongata ba li-biomarker tsa mofetše tse amanang ka thata le mefuta e itseng ea mofetše.Karolo ea DNA methylation aberrations e khetholloang ke UCOM ho tumorigenesis, tsoelo-pele ea hlahala, le metastasis ha e e-s'o tsejoe nakong ea ho lahleheloa le ho fumana boitsebiso ba sele 'me ho hlokahala hore ho hlahlojoe ka botlalo.Thahasello e 'ngoe e kholo e mabapi le ho kenyeletsoa ha mokhoa oa homogeneity oa li-UCOM tse nang le matšoao a ikhethileng a lisele ka ts'epo ea ho atamela ho fumana matšoao a mofetše le ho tsebahatsa tšimoloho ea lisele tsa tumor ka tsela e fapaneng.Li-UCOM e ka ba sesebelisoa se nepahetseng sa ho thibela mofetše, ho lemoha mofetše, le ho sireletsa le ho felisa mofetše.
Fana ka tshehetso
Mosebetsi ona o ile oa tšehetsoa ke Lenane la Naha la Bohlokoa la R&D la Chaena (Thuso ea No. 2022BEG01003), Motheo oa Naha oa Saense ea Tlhaho oa Chaena (Grant Nos. 32270645 le 32000505), Thuso e tsoang ho Komisi ea Bophelo ea Profinse ea Heilongjiang (Thuso ea No. 2020-111) , le Thuso e tsoang ho Heze Science and Technology Institute (Grant No. 2021KJPT07).
Khohlano ea polelo ea thahasello
Wei Li ke Mookameli oa R&D oa Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu o sebeletsa Botong ea Keletso ea Saense ea Epiprobe.W. Yu le Epiprobe ba amohetse litokelo tsa molao tse ntseng li emetse tse amanang le mosebetsi ona.Bangoli ba bang kaofela ba phatlalatsa hore ha ho na lithahasello tse qothisanang lehlokoa.
Menehelo ea mongoli
E thehiloe le ho rala morero: Chengchen Qian le Wenqiang Yu.
O ngotse pampiri: Chengchen Qian.
E entse lipapiso: Chengchen Qian.
E hlahlobile le ho hlophisa buka e ngotsoeng ka letsoho: Xiaolong Zou, Wei Li, Yinshan Li le Wenqiang Yu.
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doi: 10.20892/j.issn.2095-3941.2023.0313
Nako ea poso: May-07-2024