Nlele Obere
Ebe nchekwa megide ọrịa kansa: naanị ihe nrịbama ọrịa kansa zuru ụwa ọnụ
Chengchen Qian1, Xiaolong Zou2, Wei Li1,3, Yinshan Li4, Wenqiang Yu5
1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, China;2 Department of General Surgery, Ụlọ Ọgwụ Njikọ Mbụ nke Harbin Medical University, Harbin 150001, China;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, China;4 Ụlọ ọgwụ ndị mmadụ nke Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan 750002, China;5Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute & Laboratory of RNA Epigenetics, Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China
ABSTRACT
Ọrịa cancer bụ ihe kacha ebute ọnwụ n'ụwa niile.Nchọpụta ọrịa kansa n'oge nwere ike belata ọnwụ nke ụdị ọrịa kansa ọ bụla;Otú ọ dị, ndị na-achọpụta ihe ndị na-emepụta ihe n'oge dị irè adịghị maka ọtụtụ ụdị ọrịa cancer.Methylation DNA bụ ihe bụ isi ebumnuche maka mmasị n'ihi na DNA methylation na-emekarị tupu mgbanwe mkpụrụ ndụ ihe nketa ndị ọzọ achọpụtara.Mgbe ị na-enyocha njirimara ọrịa kansa na-eji usoro ntuziaka na-edobe usoro maka DNA methylation, usoro nke ọrịa cancer zuru ụwa ọnụ naanị akara (UCOMs) apụtala dị ka ndị na-agba ọsọ siri ike maka nchọpụta mbụ nke ọrịa cancer.Ọ bụ ezie na uru ụlọ ọgwụ nke ndị na-ahụ maka ọrịa kansa ugbu a na-ebelata site na mmetụta dị ala na / ma ọ bụ nkọwa dị ala, njirimara pụrụ iche nke UCOM na-eme ka ọ pụta ìhè n'ụlọ ọgwụ.Nkwenye nke ike ụlọ ọgwụ nke UCOM na ngụgụ, cervical, endometrial, na urothelial cancer na-akwado ngwa nke UCOM n'ọtụtụ ụdị ọrịa cancer na ọnọdụ ahụike dị iche iche.N'ezie, ngwa nke UCOM dị ugbu a na nyocha na-arụsi ọrụ ike na nyocha ọzọ na nchọpụta mmalite nke ọrịa cancer, nchọpụta enyemaka, ịdị irè ọgwụgwọ, na nleba anya nlọghachi.Usoro molekụla nke UCOM ji achọpụta ọrịa kansa bụ isiokwu ndị ọzọ dị mkpa a ga-enyocha.Ngwa nke UCOM n'ọnọdụ ọnọdụ ụwa na-achọkwa mmejuputa na mmezi.
OKWU
Nchọpụta ọrịa cancer;nyocha ọrịa kansa;DNA methylation;epigenetics nke ọrịa cancer;ọrịa cancer biomarkers
Ihe mere anyị ji chọọ ọhụrụ ngwa ngwa biomarkers?
Ka a lụsochara ọrịa cancer ọgụ ihe karịrị otu narị afọ, ọrịa cancer ka bụ ihe iyi egwu kacha egbu ụmụ mmadụ.Ọrịa cancer ka bụ nchegbu ahụike zuru ụwa ọnụ na nde 19.3 ọhụrụ na ihe fọrọ nke nta ka ọ bụrụ nde 10 na-eme atụmatụ na 20201. N'afọ 2020, a chọpụtara na ọrịa cancer ọhụrụ dị nde 4.6 na China, na-aza 23.7% nke ọrịa cancer ọhụrụ n'ụwa nile dịka GLOBOCAN1 si kwuo.Ọzọkwa, ihe dị ka nde mmadụ 3 nwụrụ n'ihi ọrịa kansa na China na 2020, nke bụ 30% nke ọnwụ metụtara ọrịa kansa zuru ụwa ọnụ.Ndekọ ọnụ ọgụgụ ndị a gosiri na China nọ n'ọkwa mbụ na ọnụọgụ ọrịa kansa na-anwụ.Ọzọkwa, ọnụ ọgụgụ nlanarị ọrịa cancer afọ 5 bụ 40.5%, nke bụ 1.5 ugboro dị ala karịa afọ ndụ ndụ afọ 5 na United States2,3.Ọnụnọ ndụ dị ala na ọnụ ọgụgụ ọnwụ dị elu na China karịa na mba ndị nwere akara mmepe mmadụ dị elu na-atụ aro na usoro mgbochi ọrịa cancer na-akwụ ụgwọ nke ọma na nke dị ọnụ ala dị mkpa ngwa ngwa.Nchọpụta mbụ nke ọrịa cancer bụ otu n'ime ihe kachasị mkpa na usoro nlekọta ahụike.Nchọpụta ọrịa kansa n'oge nwere ike imeziwanye amụma na ịlanarị n'oge mmalite n'ihe fọrọ nke nta ka ọ bụrụ ụdị ọrịa cancer niile4.Usoro nyocha nke ọma emela ka mbelata dị ukwuu n'ọkwa na ọnụọgụ ọnwụ nke cervical, ara, colorectal, na prostate cancer.
Otú ọ dị, iji nweta nchọpụta mbụ nke ọrịa cancer abụghị ọrụ dị mfe.Inyocha bayolọji na amụma gbasara ọrịa kansa mbụ, ịchọpụta na imezi ihe ndị na-achọpụta ihe nrịba ama n'oge a pụrụ ịdabere na ya, na imepe teknụzụ ịchọpụta mmalite nke nwere ike ịnweta na nke ziri ezi bụbu ihe mgbochi kachasị na usoro a.Nchọpụta kpọmkwem nke ọrịa cancer nwere ike ịmata ọdịiche dị njọ na ọnya ọjọọ, nke na-enyere aka izere usoro ndị na-adịghị mkpa ma na-eme ka nlekọta ọrịa dịkwuo mfe.Usoro nchọpụta mmalite dị ugbu a gụnyere biopsies dabere na endoscope, onyonyo ahụike, cytology, immunoassays, na nyocha biomarker5-7.N'ịbụ ndị na-etinye aka na nke dị oke ọnụ, biopsies dabeere na endoscope na-ebu ibu dị arọ dị ka isi usoro ahụike na-adabere na ndị ọrụ ọkachamara.Dị ka cytology, ụzọ nyocha abụọ ahụ dabere na ndị ọkachamara ahụike ma dabere na mkpebi onwe onye yana arụmọrụ na-adịghị mma8.N'ụzọ dị iche, immunoassays bụ nke ukwuu ezighi ezi, n'ihi na ọnụ ọgụgụ dị elu ụgha dị elu.Onyonyo ahụike, dị ka usoro nyocha, chọrọ akụrụngwa dị oke ọnụ na ndị ọkachamara pụrụ iche.N'ihi ya, onyonyo ahụike nwere oke oke n'ihi nnweta dị ala.N'ihi ihe ndị a niile, ndị na-ahụ maka biomarkers yiri ka ọ bụ nhọrọ kacha mma maka nchọpụta mmalite nke ọrịa kansa.
Mmekọrịta na: Yinshan Li na Wenqiang Yu
Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn
ORCID ID: https://orcid.org/0009-0005-3340-6802 na
https://orcid.org/0000-0001-9920-1133
natara Ọgọst 22, 2023;nabatara Ọktoba 12, 2023;
E bipụtara na Nọvemba 28, 2023 na ntanetị.
Dị na www.cancerbiomed.org
©2023 Ọrịa Cancer Biology & Ọgwụ.Creative Commons
Nkwanye-Ikikere Mba Nile Na-abụghị Azụmaahịa 4.0
A na-ahazi ihe ndị na-emepụta ihe ugbu a dị ka protein, ihe nrịbama DNA mutation, ihe nrịbama epigenetic, chromosomal abnormalities, ihe nrịbama RNA nke enwetara ozugbo site na etuto ahụ, ma ọ bụ iberibe etuto enwetara na-apụtaghị ìhè site na mmiri nke anụ ahụ.Ihe nrịbama protein bụ ihe nrịbama biomarkers kachasị etinyere na nyocha ọrịa kansa na nyocha.Ndị na-ahụ maka protein biomarkers, dị ka ndị na-enyocha bio-markers, na-ejedebe site na ọdịdị nke ọnya na-adịghị mma na-emetụta ya, nke na-eduga n'ịchọpụta nrịanrịa na ọgwụgwọ, dị ka a kọrọ maka α-fetoprotein na prostate-specific antigen (PSA) 9,10.Ihe nrịbama RNA na-agụnye usoro okwu mkpụrụ ndụ ihe nketa na ihe nrịbama RNA ndị ọzọ na-abụghị koodu. Enwere ike ịhụ nchikota nke mkpụrụ ndụ ihe nketa RNA site na iji ihe nrịbama mmamịrị, nke uche ya adịghị mma (60%) maka etuto isi, na nchọpụta nke nwere ike ịchọta ya. na-emetụta ọdịdị nbibi dị mfe nke RNA na gburugburu ebe obibi11.Ihe nrịbama mkpụrụ ndụ ihe nketa na epigenetic abụọ na-eche nsogbu nke ukwuu na etuto ahụ na njedebe na ụdị ọrịa kansa.
DNA methylation abụrụla onye ndoro-ndoro siri ike dị ka onye na-achọpụta biomarker nke mbụ kemgbe Feinberg jikọtara ya na ọrịa kansa na 198312. A na-ahụta DNA methylation aberrations n'oge niile nke ọrịa cancer, dịka mmalite nke ọkwa mbụ.Aberrant DNA hypermethylation na-emekarị na agwaetiti CpG na ndị na-akwalite mkpụrụ ndụ ihe nketa iji gbochie ndị na-egbochi tumor13,14.Nnyocha egosiwokwa na DNA hypermethylation na-adịghị mma na-etinye aka na nhazi nke ndị na-ahụ maka mmepe15.Ndagwurugwu DNA methylation, nke a na-ejikọkarị ya na ndị na-ahụ maka mmepe na ọrịa hypermethylated, nwere ike ịgbanwe usoro okwu mkpụrụ ndụ ka ọ bụrụ ọnọdụ DNA methylation kwụsiri ike ma belata njikọ methylated histone H3K27me3 na proteins polycomb jikọtara ya16,17.
N'ime ọnụ ọgụgụ buru ibu nke DNA methylation markers, ọtụtụ ejirila nke ọma debuted na ahịa;Otú ọ dị, ihe nrịbama DNA methylation nke a na-ere ahịa ugbu a na akụkụ nchọpụta achọpụtabeghị nke ọma n'ụzọ zuru ezu ike ịchọta ọrịa cancer n'oge n'ihi ọtụtụ ihe.Ọ bụ ezie na-egosipụtakarị arụmọrụ anabatara site na iji ozi nchekwa data, ndị biomarkers na-arụkarị ọrụ na-adịchaghị mma na ụwa n'ezie n'ihi n'eziokwu na ihe nlele ụwa na-adịkarị mgbagwoju anya ma ọ bụghị dị ka onye nnọchiteanya dịka ndị ahọpụtara na ọdụ data.Nchọpụta mmalite nke ọtụtụ ọrịa cancer nke ọgbọ na-abịa egosila na ọ nwere naanị 16.8% na 40.4% n'ime ọrịa cancer ogbo I na II, n'otu n'otu.Nnwale nchọpụta mmalite chọrọ nkwụsi ike ka ukwuu yana ndị na-ahụ maka biomarkers ziri ezi.
Naanị ihe nrịbama ọrịa cancer zuru ụwa ọnụ (UCOM) site na iji usoro nhazi ntuziaka (GPS)
N'agbanyeghị ọtụtụ iri afọ nke nchọpụta ọrịa cancer, a chọpụtabeghị mgbochi na ọgwụgwọ na-eju afọ.A chọrọ usoro ọhụrụ iji mee ka ndị nchọpụta nwee ike nyochaa ọrịa kansa nke ọma.N'ime afọ 23 gara aga, akara ngosi ọrịa kansa 6, dị ka ịgbanahụ apoptosis, mbuso agha anụ ahụ & metastasis, wdg, agbasawanyela ruo 14 site n'itinye njiri mara dị ka mmegharị epi-genetic reprogramming nonmutational na polymorphic microbiomes20,21.Ka ekpughere nkọwa ndị ọzọ metụtara ọrịa kansa, a na-ewebata echiche ndị ọzọ na nyocha ọrịa kansa.Nnyocha ọrịa cancer ejirila nke nta nke nta bata n'ọhụụ n'akụkụ abụọ (mmekọrịta na onye ọ bụla).Site na mmepe nke oncology ziri ezi n'afọ ndị na-adịbeghị anya, ihe nyocha nke ọrịa cancer na-elekwasị anya na-adabere na ọgwụgwọ ezubere iche nke onwe ya na ụdị ọrịa cancer22.Ya mere, ndị na-ahụ maka ọrịa kansa achọpụtala n'oge na-adịbeghị anya lekwasịrị anya na ụdị ọrịa kansa a kapịrị ọnụ, dị ka PAX6 forcervical cancer23 na BMP3 maka cancer colorectal24.Arụmọrụ nke biomarkers ndị a kpọmkwem maka ụdị ọrịa kansa dịgasị iche iche, mana ọ ka na-agaghị ekwe omume maka ndị nwere ike ịme nyocha maka ọrịa cancer niile n'otu oge n'ihi mmachi nke nnweta sample ndu na ọnụ ahịa dị elu.Ọ ga-adị mma ma ọ bụrụ na anyị nwere ike ịchọpụta otu, nke siri ike biomarker nke dị irè maka ụdị ọrịa kansa ọ bụla n'oge dị nso.
Iji nweta ezigbo ebumnobi dị otú ahụ, a ga-ahọpụtarịrị onye na-achọ biomarker ka mma n'ime ndepụta nke ụdị biomarker nwere ike ime.DNA methylation aberrations, n'etiti mkpụrụ ndụ ihe nketa niile na profaịlụ epigenetic, ka amara na ọ metụtara ọrịa kansa ma bụrụ ụfọdụ n'ime ihe mbụ, ma ọ bụrụ na ọ bụghị nke mbụ, ọrịa kansa metụtara ọrịa na-eme n'usoro oge.Nnyocha nke DNA methylation malitere n'isi ụtụtụ, mana enweghi ụzọ nyocha egbochila ya.N'ime nde 28 nwere ike methylated CpG saịtị na genome, a ga-achọpụta ọnụọgụ nwere ike ijikwa ma kwekọọ na genome iji ghọta nke ọma tumorigenesis.Sequencing dum genome bisulfite (WGBS), nke a na-ewere dị ka ụkpụrụ ọla edo nke usoro DNA methylation, nwere ike kpuchie 50% nke Cs na mkpụrụ ndụ kansa n'ihi ọdịdị nke ọgwụgwọ bisulfite nke na-agbaji iberibe DNA ma na-ebelata mgbagwoju anya genome n'oge. mgbanwe nke Cs-to-Ts25.Ụzọ ndị ọzọ, dị ka ibe 450k, na-ekpuchi naanị 1.6% nke genome methylation.Dabere na data 450k, otu DNA methylation detection panel nwere mmetụta 35.4% maka ụdị 6 nke ọrịa cancer nke m26.Mmachi nke ụdị ọrịa kansa, arụmọrụ adịghị mma, na mkpọtụ sitere na ụzọ nchọpụta n'ime usoro nyocha abụrụla ihe mgbochi kachasị ukwuu maka ogwe nchọpụta pan-cancer.
Iji nyochaa nke ọma usoro epigenetic nke mkpụrụ ndụ n'oge tumorigenesis na metastasis, anyị mepụtara GPS pụrụ iche maka nchọpụta DNA methylation genome, nke na-ekpuchi ihe ruru 96% nke saịtị CpG na 0.4 ijeri na-agụ25.GPS bụ usoro nke usoro bilateral na-eji 3′ njedebe DNA nke methyl-cytosines na-adịghị agbanwe agbanwe mgbe ọgwụgwọ bisulfite gachara nke na-eduzi nhazi nke ngụkọta DNA methylation nke njedebe 5′ site na usoro njedebe ụzọ abụọ (Njirimara 1)25.Strand methyl-cytosine na-eduzi, na-eme dị ka eriri ndebiri, na-enyere aka na nhazi mpaghara GC dị elu nke na-eweghachite data nsonye kachasị agbahapụ na WGBS omenala.Akụkụ dị elu nke GPS na-enye ozi methylation DNA buru ibu, nke na-enye anyị ohere inyocha profaịlụ methylation nke ọrịa kansa na mkpebi dị elu nke ukwuu na mpaghara ndị a nyochabeghị mbụ.
GPS na-enye anyị ngwá ọrụ dị ike iji nyochaa ịdị n'otu nke ọrịa cancer, nke nwere ike ime ka nchọpụta ọrịa dị mfe ma nwee ike ịchọta nkọwa zuru ụwa ọnụ maka tum-origenesis na metastasis.Mgbe ị na-enyocha data GPS nke ahịrị mkpụrụ ndụ kansa, a na-ezutekarị ihe pụrụ iche.Enwere ọtụtụ mpaghara ndị yiri ka hypermethylated na-adịchaghị mma n'ọtụtụ ụdị ụdị ọrịa kansa.Emechara kwado nchọta a na-atụghị anya ya ka ọ bụrụ UCOM.Ihe karịrị 7,000 samples sitere na ụdị ọrịa kansa 17 dị na nchekwa data Cancer Genome Atlas (TCGA) ka enyochala, n'ime nke anyị chọpụtara UCOM mbụ, HIST1H4F, mkpụrụ ndụ metụtara histone nke hypermethylated na ụdị ọrịa cancer niile27.A chọtara usoro UCOM wee kwado ya na nchekwa data TCGA, nchekwa data Gene Expression Omnibus (GEO), na ihe nlele ụlọ ọgwụ n'ezie.Ka ọ dị ugbu a, HIST1H4F, PCDHGB7, na SIX6 ka ahụrụla ma kwado ya dị ka UCOM.Nchọpụta a na-atụghị anya ya nke UCOM na-enye azịza siri ike maka mkpa nchọpụta mbụ nke ọrịa cancer.UCOM na-enye ihe ngwọta maka nchọpụta otu akara nke ọtụtụ ọrịa cancer.
Njirimara nke UCOM
Na nkwado, egosiri UCOM iji gosipụta njirimara anọ dị mkpa na-enyere ndị UCOM aka karịa ịdị irè nke ndị na-ahụ maka biomarkers ugbu a (Nyocha 2).
Pụrụ iche na malignancy
UCOMs pụrụ iche na ọnya ọrịa kansa ma ọ bụ tupu ọrịa kansa yana mgbanwe physiologic nkịtị anaghị emetụta ya.Ụfọdụ n'ime ihe nrịbama metụtara ọrịa cancer ugbu a bụ nke etinyere n'ọtụtụ ebe na nchọpụta mmalite na/ma ọ bụ nyocha ebutela nchọpụta nrịanrịa.A na-achọpụtakwa ọkwa PSA dị elu, ngwá ọrụ nyocha ụlọ ọgwụ kwadoro na ọnọdụ adịghị mma, dịka hyperplasia prostate na prostatitis10.Nchọpụta nrịanrịa na ọgwụgwọ oke nke na-ebute na-eduga n'ịdị mma ndụ mbelata n'ihi eriri afọ, urinary na nsogbu mmekọahụ28.Ndị ọzọ dabere na protein na biomarkers nke a na-ejikarị eme ihe na ọnọdụ ụlọ ọgwụ, dị ka CA-125, enyebeghị uru ọ bụla dị ịrịba ama mgbe ha na-ebute nyocha nrịanrịa na ọgwụgwọ29.Nkọwa dị elu nke UCOMs maka ajọ njọ na-ezere mkpirisi ndị a.UCOM, PCDHGB7, na-akọwa nke ọma ọdịiche dị elu nke squamous intraepithelial ọnya (HSILs) na ọrịa cancer cervical site na nlele nkịtị na ọnya squamous intraepithelial (LSILs), ebe ọtụtụ ihe nrịbama ndị ọzọ nwere ike ịmata ọdịiche dị n'ọrịa cancer cervical na sample30.Ọ bụ ezie na PCDHGB7 achọpụtaghị nnukwu ọdịiche dị n'etiti endometrium nkịtị na hyperplasia endometrial, a na-achọpụta ọdịiche dị ukwuu n'etiti endometrium nkịtị na hyperplasia atypical, na ọbụnadị ndịiche ka ukwuu na-achọpụta n'etiti endometrium nkịtị na ọrịa cancer endometrial (EC) dabere na PCDHGB731.UCOM pụrụ iche na ọnya ọjọọ na ọdụ data yana ihe nlele ụlọ ọgwụ.Site n'echiche onye ọrịa, UCOM pụrụ iche na-ebelata ọnụ ụzọ maka ịghọta mgbagwoju anya nrịbama nke ụdị biomarkers dị iche iche na-adịghị mma na nchekasị kwekọrọ n'oge usoro nyocha.Site n'echiche onye dọkịta, UCOM pụrụ iche na-ekewa ọrịa ọjọọ na ọnya na-adịghị mma, nke na-enyere aka n'ichepụta ndị ọrịa ma na-ebelata usoro ahụike na-enweghị isi na ọgwụgwọ.Ya mere, UCOM pụrụ iche na-ebelata nkwụghachi ụgwọ sistemu ahụike, na-ebelata nsogbu sistemu, ma na-enye ndị nọ na mkpa ohere ọgwụ karịa.
Ọgụgụ 1 Atụmatụ usoro ọrụ GPS maka nchọpụta DNA methylation25.Ahịrị isi awọ: ndenye usoro DNA;ahịrị uhie: DNA mesoro T4 DNA polymerase, dochie cytosine na 5′-methylcytosine na njedebe 3′ nke ntinye;acha anụnụ anụnụ C na M: cytosine methylated;acha anụnụ anụnụ C: cytosine unmethylated;odo T: thymine25.
Ihe niile ma ọ bụ ihe ọ bụla
UCOM dị naanị na mkpụrụ ndụ kansa ma chọpụta ya nke ọma n'ihe fọrọ nke nta ka ọ bụrụ mkpụrụ ndụ kansa niile.HIST1H4F kwadoro ka ọ bụrụ hypermethylated n'ihe fọrọ nke nta ka ọ bụrụ ụdị tumor niile mana ọ bụghị na nlele nkịtị27.N'otu aka ahụ, PCDHGB7 na SIX6 egosikwara na ha nwere hypermethylated na ụdị tumor niile mana ọ bụghị na nlele nkịtị30-32.Àgwà ọma a pụrụ iche na-eme ka arụmọrụ nke UCOM dịkwuo mma n'ihe gbasara oke nchọpụta na nghọta.Dị ka 2% nke mkpụrụ ndụ kansa nwere ike ịdị iche na nlele, na-eme ka UCOM bụrụ ihe na-ahụ maka biomarker karịa ọtụtụ ndị na-ahụ maka biomarkers30. Dị ka biomarker eji achọpụta ọrịa cancer colorectal, mgbanwe KRAS dị naanị na ihe dịka 36% nke ọrịa cancer colorectal. na-atụ aro ike ịchọpụta ọrịa adịghị mma33.Mmụba dị ala nke mmụgharị KRAS na ọrịa cancer colorectal na-amachi KRAS yana njikọ ndị ọzọ na-ahụ maka biomarkers.N'ezie, nchikota nke biomarkers nwere ike iyi ihe na-ekwe nkwa na mbụ, ma ọ bụghị mgbe niile na-emepụta ihe na-eju afọ mgbe ọ na-egosipụta mkpọtụ ka ukwuu na nyocha nchọpụta ma na-agụnyekarị usoro nyocha siri ike karị.N'ụzọ dị iche, PCDHGB7 na UCOM ndị ọzọ dị na ọrịa cancer niile.Ndị UCOM na-achọpụta ihe ndị na-akpata ọrịa kansa n'ụdị ụdị ọrịa kansa dị iche iche na nkenke zuru oke ebe ha na-ekpochapụ usoro nyocha mkpọtụ mkpọtụ siri ike.Ọ naghị esiri ike ịchọpụta ọrịa kansa n'ọtụtụ nlele, mana ọ na-esiri ike ịchọpụta ọrịa kansa na obere nlele.UCOM nwere ike ịchọpụta obere ọrịa kansa.
Ọgụgụ 2 Njirimara UCOM.
Nchọpụta ọrịa kansa na-ebute ụzọ mgbanwe pathological
Enwere ike ịhụ UCOM n'ọkwa tupu ọrịa kansa tupu mgbanwe ọrịa.Dị ka epigenetic biomarkers, UCOM abnormalities na-eme na mbụ ogbo karịa phenotypic abnormalities na a na-achọpụta na n'oge tumorigenesis, ọganihu, na metastasis34,35.Mmetụta uche nke UCOM ka oge na-aga na-eme ka arụmọrụ UCOM dịkwuo elu n'ịchọpụta ọrịa kansa na mmalite nke ọrịa cancer.Nchọpụta ọrịa kansa mbụ dabere na biopsies na cytology nwere ike isiri ọbụna ndị ọkachamara n'ihe gbasara ọrịa ike.Otu biopsy enwetara site na colposcopy ka akọpụtala dị ka ihe dị mma na 60.6% nke nlele HSIL+.Achọrọ biopsies agbakwunyere maka ọtụtụ ọnya iji mụbaa uche36.N'ụzọ dị iche, UCOM, PCDHGB7, nwere mmetụta nke 82% maka ihe atụ HSIL +, karịrị mmetụta nke biopsies na ọtụtụ biomarkers30.Ihe nrịbama methylation, FAM19A4, nwere mmetụta nke 69% maka CIN2+, nke yiri cytology, mana enweghị ike ikewapụ CIN1 na ihe nlele nkịtị37.Egosiputara UCOM ka ọ bụrụ ihe na-achọpụta biomarker n'oge karịa.Tụnyere ndị ọkachamara n'ọrịa gbasara ahụmihe, UCOM nwere nhụta dị elu maka ọrịa kansa mmalite, nke n'aka nke ya na-enye aka kwalite amụma ọrịa kansa na nlanarị30.Na mgbakwunye, UCOM na-enye ikpo okwu nchọpụta nke enwere ike ịnweta mpaghara enweghị ndị ọkachamara n'ihe gbasara ọrịa ma na-emeziwanye arụmọrụ nchọpụta.Site na nleba anya na usoro nchọpụta otu, nchọpụta UCOM na-arụpụta nsonaazụ kwụsiri ike ma dị mfe ịkọwa nke dabara adaba na usoro nyocha nke chọrọ ndị ọrụ ọkachamara na akụrụngwa ahụike ole na ole.
Ọ dị mfe ịchọpụta
Ụzọ ndị dị ugbu a maka nchọpụta DNA methylation na-agbagwoju anya ma na-ewe oge.Ọtụtụ n'ime ụzọ ndị a chọrọ mgbanwe bisulfite, nke na-ebute mfu na ogo nlele na ikekwe na-arụpụta nsonaazụ na-akwụghị ọtọ na ezighi ezi.Mmụgharị na-adịghị mma nke ọgwụgwọ bisulfite kpatara nwere ike iduga mgbagwoju anya maka ndị dọkịta na ndị ọrịa ma na-etinyekwu aka na nsonye na / ma ọ bụ usoro ọgwụgwọ.Ya mere, anyị gbanwekwara usoro nchọpụta UCOM iji zere ọgwụgwọ bisulfite nwere nsogbu nke ihe nlele ahụ, nabata ihe ngwa ụlọ ọgwụ chọrọ, ma kwalite nnweta.Anyị mepụtara usoro ọhụrụ site na iji methylation-sensitive restriction enzymes jikọtara ya na ezigbo oge fluorescent quantitative PCR (Me-qPCR) iji chọpụta ọkwa methylation nke UCOM n'ime 3 h na-eji usoro njikwa dị mfe (Nyocha 3).Me-qPCR nwere ike ịnabata ụdị nlele dị iche iche, dị ka nchịkọta ahụike nke nsị anụ ahụ yana nlele mmamịrị chịkọtara onwe ya.Enwere ike ịhazi ihe nlele ụlọ ọgwụ anakọtara, chekwaa ma gaa n'ihu n'ụzọ dị mfe site na iji mmịpụta DNA ahaziri ahazi yana akpaaka.Enwere ike itinye DNA ahụ ewepụtara ozugbo n'elu ikpo okwu Me-qPCR maka mmeghachi omume otu ite na nsonaazụ nhapụta.Mgbe nyochachara nsonaazụ dị mfe site na iji ụdị diagnostic dabara adaba ma kwado ya na ụdị ọrịa kansa akọwapụtara, a na-atụgharị ma gosipụta mkpebi ikpeazụ nke nsonaazụ UCOM dị ka uru ọkara.Ikpo okwu Me-qPCR na-eme ka omenala bisulfite-pyrosequencing dị na nchọpụta UCOM ka ọ na-echekwa 3 h ofbisulfite mgbanwe, dị ka EZ DNA Methylation-Gold kit protocol.Usoro nchọpụta methylation ọhụrụ na-eme ka nchọpụta UCOM kwụsie ike, zie ezi, yana ịnweta30.
Ọgụgụ 3 Usoro nchọpụta nke UCOM.Ụdị nlele gụnyere BALF, ahịhịa pap, na/ma ọ bụ mmamịrị chịkọtara onwe ya.Enwere ike ịnabata usoro mmịpụta DNA na onye nrụpụta akpaka, nke qPCR nwere ike ịchọpụta ngwaahịa ya ozugbo.
Ngwa nke UCOM
Ọrịa cancer akpa ume
Ọrịa cancer akpa ume bụ nke abụọ a na-achọpụtakarị na ọrịa kansa na-egbu egbu n'ụwa niile, na-akpata 11.4% nke ọrịa ọhụrụ yana 18.0% nke ọnwụ ọhụrụ1.N'ime nchọpụta niile, 85% bụ ọrịa cancer akpa ume na-abụghị obere cell (NSCLC) na 15% bụ ọrịa cancer akpa ume obere cell (SCLC), nke nwere ọkwa dị elu nke malignancy38.Nleba anya na-agbakọ obere dose (LDCT) bụ usoro nyocha nke akwadoro ugbu a maka ọrịa cancer akpa ume na egosiri na ọ ga-eme ka nchọpụta mmalite na belata ọnwụ6;Otú ọ dị, n'ihi obere nkọwapụta na ohere adịghị mma, LDCT ka na-eje ozi dị ka usoro nyocha nke na-eju afọ, dịka ihe nrịbama ọrịa cancer ndị ọzọ na-emekarị, dị ka CEA39.Ọnụ ego na ikike nke nyocha na-efunahụ na nyocha nke atụmatụ nyocha LDCT na-egbochi ọganihu nke nyocha ọrịa kansa akpa ume40.HIST1H4F, UCOM, nwere nnukwu ikike dị ka ihe nchọpụta mmalite nke biomarker na bronchoalveolar fluid (BALF) sample27.HIST1H4F bụ hypermethylated na nku ume adenocarcinoma na akpa ume squamous cell carcinoma, na-achọpụta kpọmkwem 96.7% na uche nke 87.0% (Onyonyo 4A), na pụrụ iche arụmọrụ maka ogbo I cancer27.HIST1H4F nwere nkọwapụta nke 96.5% yana uche nke 85.4% maka NSCLC, yana 96.5% na 95.7%, n'otu n'otu, maka SCLC27.Na mgbakwunye, ihe nlele nke ụdị ọrịa kansa asatọ ndị ọzọ, gụnyere pancretic na cancer colorectal, akwadola na HIST1H4F bụ hypermethylated na ụdị asatọ niile27.
Ọrịa cervical
Ọrịa kansa cervical bụ nke anọ a na-achọpụtakarị ọrịa kansa yana nke anọ na-ebute ọnwụ kansa na ụmụ nwanyị na 2020, na-aza 3.1% nke ikpe ọhụrụ yana 3.4% nke ọnwụ metụtara ọrịa kansa n'ụwa niile1.Iji kpochapụ ọrịa cancer cervical n'afọ 2030, dị ka WHO tụpụtara, nchọpụta mmalite nke ọrịa cancer cervical bụ ihe dị mkpa.Ọ bụrụ na achọpụtara ya n'oge mmalite, ọnụọgụ ndụ nke afọ ise na-erute 92% na ọrịa kansa cervical invasive41.Ntuziaka American Cancer Society (ACS) na-atụ aro ule cytology cervical, ule HPV bụ isi, ma ọ bụ cotests maka nyocha42.Cytology cervical na-akpa ike ma nwee ike ịchọpụta naanị 63.5% nke ikpe CIN2+37.
PCDHGB7, n'ụzọ dị iche, arụla ọrụ nke ọma nke ọma site na iji Pap smears na nzuzo nzuzo, ma nwee ike ịmata ọdịiche dị na HSIL na LSIL nke ọma n'oge mmalite mmalite.PCDHGB7 naanị nwere uche nke 100.0% yana nkọwapụta nke 88.7% maka ọrịa kansa cervical (Onyonyo 4B), yana mmetụta 82.1% na 88.7% nkọwapụta maka HSIL+ samples30.PCDHGB7 nwekwara 90.9% uche na 90.4% nkọwapụta na ikpu secretion sample maka cervical cancer, nke dị mfe ịnakọta30.Mgbe ejikọtara ya na ule dị elu (hr) HPV ma ọ bụ Thinprep Cytology Test (TCT), PCDHGB7 nwere mmụba nke 95.7% na nkọwapụta nke 96.2%, karịa nke ule hrHPV (20.3%), TCT (51.2%). ), na abụọ jikọtara (57.8%) maka cervical cancer30.E gosikwara PCDHGB7 ka ọ bụrụ hypermethylated na ụdị ọrịa kansa iri na asaa sitere na nchekwa data TCGA, na-egosi na ọ dabara na ezinụlọ UCOM30.
Ọnụọgụ 4 UCOM ka akwadoro n'ụdị ọrịa kansa anọ na nnukwu ọmụmụ ụlọ ọgwụ.A. Ịrụ ọrụ nke HIST1H4F, UCOM, na nchọpụta ọrịa cancer akpa ume nke ihe nlele 508.B. Arụmọrụ PCDHGB7, UCOM, na nchọpụta ọrịa kansa cervical nke ihe atụ 844.C. Ịrụ PCDHGB7, UCOM, na nchọpụta ọrịa cancer endometrial nke 577 endometrial Pap na Tao brush samples.D. Ịrụ ọrụ nke SIX6, UCOM, na nchọpụta ọrịa cancer urothelial nke ihe atụ 177.
EC
EC bụ otu n'ime ọrịa kansa usoro ọmụmụ ụmụ nwanyị a na-ahụkarị n'ụwa niile, yana ihe dị ka nde mmadụ 4.2 ọhụrụ na 1% nke ọnwụ metụtara ọrịa kansa kwa afọ1.Site na nchoputa na-aga nke ọma n'oge dị nso, EC nwere ike ịgwọta ma nwee ọnụọgụ ndụ afọ 5 nke 95% maka ọrịa cancer ogbo I.Ndị ọrịa nwere mgbaàmà, dị ka ọbara ọgbụgba uterine na-adịghị mma, na-enweta nyocha ụlọ ọgwụ oge ụfọdụ ma na-eme usoro biopsy na-egbu mgbu na nke na-egbu mgbu, n'agbanyeghị na 5%-10% na-emecha mepụta EC43.Ụda ụda transvaginal, dị ka usoro nchọpụta a na-ahụkarị, enweghị ntụkwasị obi nke ukwuu n'ihi enweghị ike ikewapụta ọdịiche dị mma na mgbanwe endometric dị njọ yana ọnụego ụgha dị elu44.
Ntule yiri nke serum CA-125, EC biomarker nke etinyere n'ọtụtụ ebe, yana PCDHGB7 ka emere.Serum CA-125 nwere uche nke 24.8%, nke na-egosi na CA-125 bụ akara na-ezughị ezu maka EC n'agbanyeghị kpọmkwem 92.3% 31.Nchọpụta PCDHGB7 site na iji ihe nlere ahịhịa Pap rụpụtara 80.65% na nkọwapụta nke 82.81% maka ọkwa ECatall, ebe ahịhịa Tao nwere mmetụta nke 61.29% yana nkọwa nke 95.31%31.Ụdị nchọpụta nchọpụta PCDHGB7, dabere na Me-qPCR, wepụtara nghọta nke 98.61%, nkọwapụta nke 60.5%, yana nkwekọ zuru oke nke 85.5%, na-eji Pap na Tao brush samples (Nyocha 4C)31.
Urothelial cancer
Ọrịa cancer urothelial, nke gụnyere eriri afo, pelvis na urethra, bụ ọrịa kansa nke asaa a na-achọpụtakarị na 2020 n'ụwa niile, na-akpata 5.2% nke ọrịa ọhụrụ yana 3.9% nke ọnwụ1.Ọrịa cancer urothelial, nke karịrị pasenti 50 nke bụ ọrịa kansa eriri afọ, bụ nke anọ a na-achọpụtakarị ọrịa kansa na United States na 2022, na-aza 11.6% nke ọrịa achọpụtara ọhụrụ3.Ihe dị ka 75% nke ọrịa cancer eriri afọ bụ nkewa dị ka ọrịa kansa eriri afọ na-adịghị emetụta akwara amachibidoro na mucosa ma ọ bụ submucosa45.A cystoscopy biopsy bụ ọkọlọtọ ọla edo maka ịchọpụta ọrịa kansa urothelial nke fluorescence in situ hybridization (FISH) na nyocha cytology mebere.Azụ na cytology na-arụ ọrụ nyocha adịghị mma, na cystoscopy bụ intrusive ma nwee ihe ize ndụ nke na-efunahụ microlesions, na-akọwahie ọnya, na nwere ike ịkpata mgbasa ma ọ bụ nlọghachi nke ọrịa cancer46.UCOM kwadoro na mbụ, PCDHGB7, ka egosiri na ọ bụ hypermethylated na ọrịa cancer urothelial, yana mpaghara dị n'okpuru usoro 0.86, na-atụ aro ikike nyocha30.Iji nwetakwuo UCOMs ma nweta ụdị ụdị nlele ọzọ, SIX6, akwụkwọ akụkọ UCOM, nyochara wee gosipụta ikike nchọpụta dị mma na mmalite nchọpụta nke ọrịa kansa urothelial site na iji urine urine n'elu ikpo okwu Me-qPCR.Nchọpụta SIX6 site na iji ihe nlele mmamịrị gosipụtara mmetụta asọmpi nke 86.7% na nkọwapụta nke 90.8% (Ọnyocha 4D), ebe ọ bụ onye na-adịghị emerụ ahụ ma dị mfe inweta32.A na-enyocha ikike nke SIX6 na nyocha metastasis na nyocha ịdị irè ọgwụgwọ ugbu a.
Ọdịnihu na ihe ịma aka
UCOM na-arụ ọrụ siri ike na enwere ike ịchọpụta ọrịa cancer dị iche iche, mana enwere ọtụtụ ọrụ fọdụrụ ime.Anyị na-agbasawanye ndepụta nke UCOM ma na-arụsi ọrụ ike na UCOM n'ụdị ọrịa kansa ndị ọzọ, gụnyere ndị siri ike ịchọpụta.Nsonaazụ nkwado sitere na ọdụ data TCGA akwadola ngwa nke UCOM n'ụdị ọrịa kansa na ọnọdụ ndị ọzọ.N'ime nyocha nke mbụ, egosiri na UCOM nwere ikike nyocha siri ike maka cholangiocarcinomas na pancreatic adenocarcinomas, nke ọ fọrọ nke nta ka ọ bụrụ ihe na-agaghị ekwe omume ịchọpụta n'oge dị nso na ụzọ nyocha ugbu a32,47.Enwere ike iji ikike ịchọpụta ọrịa cancer na-adịghị ahụkebe na UCOM na DNA tumor na-ekesa (ctDNA) site na ikpo okwu biopsy mmiri dị mma48.Ọmụmụ ihe metụtara kọmiti nchọpụta pan-cancer nke DNA dabere na plasma nyere nghọta nke 57.9%49.N'agbanyeghị ọkwa dị elu, arụmọrụ n'ozuzu ya na-egosi na a ka nwere ohere maka mmelite.
Àgwà pụrụ iche nke UCOM akwadowokwa nyocha nke UCOM nwere ike na nleba anya nleba anya ọgwụgwọ na nlọghachi azụ.Dị ka Ntụle Nzaghachi na Nyocha siri ike (RECIST), onyonyo ahụike bụ usoro akwadoro maka nleba anya ugboro ugboro na nyocha nrụpụta ọgwụgwọ, ebe a na-eji akara akara etuto naanị maka nyocha50.N'ezie, agbanyeghị, usoro onyonyo na-emetụta nke ukwuu site na ugboro na oge, ya mere na-ekpughere ndị ọrịa n'ihe egwu dị elu yana ọnụ ahịa51,52.A kwadoro SIX6 ka ọ bụrụ ihe atụ maka metastasis nke ọrịa ara ara32.Nleba anya ctDNA nke biopsy nke mmiri mmiri na-enyere aka nleba anya n'ezie n'ime ọnwa ole na ole ọrịa fọdụrụnụ tupu nchọpụta rediologic, na-egbu oge na igbochi nlọghachi ọrịa kansa metụtara nlọghachi azụ53.Nsonaazụ mbido na-egosi na UCOM na-egosipụta ọkwa nke hypermethylation cancer ozugbo ozugbo ịwachara ahụ na ọgwụgwọ32.Mmetụta uche dị elu nke UCOM gosipụtara yana ntinye n'ọtụtụ ụdị ihe nlere na-adịghị etinye aka na-enye ohere UCOM ka ọ bụrụ onye na-ahụ maka biomarker na-emegharịghachi anya ka ọ na-edobe nnabata ndị ọrịa dị elu.
N'otu oge ahụ, ịnweta ọha na eze na ule a bụ isi okwu ọzọ na-achọ mgbalị mgbakwunye.Ọ bụ ezie na anabatara mmekorita nchọpụta UCOM n'ụlọ ọgwụ ndị ọzọ na-atụ anya ịbara ọtụtụ ndị ọrịa uru, nchọpụta pro bono na nyocha emewo nke ọma na ime obodo China.UCOM chọrọ ohere ka emelitere iji tozuo dị ka ngwa nyocha enwere ike, ọkachasị maka mpaghara emepebeghị emepe.
Ọ bụ ezie na nsonaazụ ngwa UCOM na nchọpụta mmalite na-ekwe nkwa, ọtụtụ amaghị banyere UCOM dị.Site na nyocha na-arụsi ọrụ ike, a na-akwado nyocha ọzọ maka ihe kpatara UCOM ji nọrọ n'ụwa niile na ọrịa kansa.Usoro usoro iwu epigenetic dị n'okpuru UCOM kwesịrị ekwesị maka nyocha ọzọ, nke nwere ike kwado ụzọ ọhụrụ maka ọgwụgwọ ọrịa kansa.Nlaghachi na mkparịta ụka dị n'etiti etuto ahụ na ụdị dị iche iche, anyị nwere mmasị na ihe kpatara UCOM nwere ike bụrụ ihe dịpụrụ adịpụ na ọtụtụ ndị na-ahụ maka ọrịa kansa nke jikọtara ya na ụdị ọrịa kansa.Ọrụ nke UCOM-achọpụtara DNA methylation aberrations na tumorigenesis, ọganihu etuto, na metastasis ekpebibeghị na usoro nke ịla n'iyi na inwetaghachi njirimara cell ma na-achọ nyocha nke ọma.Mmasị ọzọ dị mkpa bụ n'ókè nke ntinye nke ụdị homogeneity nke UCOMs nwere akara anụ ahụ pụrụ iche na-enwe olileanya ịbịaru nso nchọta nke ọrịa kansa na njirimara nke sitere na anụ ahụ akpụ n'ụzọ ntụgharị.UCOM nwere ike ịbụ ngwá ọrụ dị mma iji gbochie ọrịa kansa, chọpụta ọrịa kansa, yana nwee ike ịgbachitere ma kpochapụ ọrịa cancer.
Nye nkwado
Ọrụ a kwadoro site na National Key R & D Program of China (Grant No. 2022BEG01003), National Natural Science Foundation of China (Grant Nos. 32270645 na 32000505), Onyinye sitere na Heilongjiang Provincial Health Commission (Grant No. 2020-111) , na onyinye sitere na Heze Science and Technology Institute (Nyere No. 2021KJPT07).
Nkwupụta esemokwu nke mmasị
Wei Li bụ onye ntụzi R&D maka Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu na-eje ozi na Board Advisory Sayensị nke Epiprobe.W. Yu na Epiprobe akwadola ikikere na-echere metụtara ọrụ a.Ndị ode akwụkwọ ndị ọzọ niile na-ekwupụta enweghị mmasị asọmpi.
Ntinye ndị odee
Chere ma chepụta ọrụ a: Chengchen Qian na Wenqiang Yu.
Dee akwụkwọ a: Chengchen Qian.
Emere ihe atụ ndị a: Chengchen Qian.
Nyochaa ma dezie ihe odide ahụ: Xiaolong Zou, Wei Li, Yinshan Li na Wenqiang Yu.
Ntụaka
1. Sung H, Ferlay J, Siegel RL, LaversanneM, Soerjomataram I, Jemal A, et al.Ọnụ ọgụgụ ọrịa kansa zuru ụwa ọnụ 2020: atụmatụ GLOBOCAN nke
ọnọdụ na ọnwụ n'ụwa niile maka ọrịa kansa 36 na mba 185.CA Cancer J Clin.2021;71: 209-49 .
2. Xia C, Dong X, Li H, Cao M, Sun D, He S, et al.Ọnụọgụ ọrịa kansa na China na United States, 2022: profaịlụ, ọnọdụ, na mkpebi.Chin MedJ (Engl).2022;135: 584-90 .
3. Siegel RL, Miller KD, WagleNS, JemalA.Ọnụọgụ ọrịa kansa, 2023. CA Ọrịa cancer J Clin.2023;73:17-48.
4. Crosby D, BhatiaS, Brindle KM, Coussens LM, Dive C, Emberton M, et al.Nchọpụta mbụ nke ọrịa kansa.Sayensị.2022;375: eeh9040.
5. Ladabaum U, Dominitz JA, KahiC, Schoen RE.Atụmatụ maka
nyocha ọrịa cancer colorectal.Gastroenterology.2020;158: 418-32 .
6. Tanoue LT, Tanner NT, Gould MK, Silvestri GA.Nyocha ọrịa cancer akpa ume.Am J Respira Crit Care Med.2015;191:19-33 .
7. Bouvard V, WentzensenN, Mackie A, Berkhof J, BrothertonJ, Giorgi-Rossi P, et al.Echiche IARC na nyocha ọrịa kansa cervical.N EnglJ Med.2021;385: 1908-18.
8. Xue P, Ng MTA, QiaoY.Ihe ịma aka nke colposcopy maka nyocha ọrịa kansa cervical na LMICs yana ngwọta site na ọgụgụ isi.BMC Med.2020;18:169 .
9. Johnson P, Zhou Q, Dao DY, Lo YMD.Na-ekesa biomarkers na nyocha na njikwa nke carcinoma hepatocellular.Nat Rev Gastroenterol Hepatol.2022;19: 670-81 .
10. Van PoppelH, Albreht T, Basu P, HogenhoutR, CollenS, Roobol M. Serum PSA dabeere na mmalite nchọpụta nke ọrịa prostate na Europe na n'ụwa nile: gara aga, ugbu a na ọdịnihu.Nat Rev Urol.2022;19:
562-72.
11. HolyoakeA, O'Sullivan P, Pollock R, Best T, Watanabe J, KajitaY,
et al.Mmepe nke ule urine multiplex RNA maka nchọpụta na stratification nke carcinoma cell mgbanwe nke eriri afo.Clin Cancer Res.2008;14: 742-9 .
12. Feinberg AP, Vogelstein B. Hypomethylation na-amata ọdịiche dị na mkpụrụ ndụ ihe nketa nke ụfọdụ ọrịa cancer mmadụ na ndị ibe ha.Ọdịdị.1983;301: 89-92.
13. Ng JM, Yu J. Onye na-akwalite hypermethylation nke mkpụrụ ndụ ihe nketa tumor dị ka ndị na-emepụta ihe na-emepụta ihe na-akpata ọrịa cancer colorectal.IntJ Mol Sci.2015;16: 2472-96 .
14. Esteller M. Ọrịa cancer epigenomics: DNA methylomes na map mgbanwe akụkọ ihe mere eme.Nat Rev Genet.2007;8: 286-98 .
15. Nishiyama A, Nakanishi M. Na-agagharị na DNA methylation odida obodo nke ọrịa cancer.Trends Genet.2021;37: 1012-27.
16. Xie W, Schultz MD, ListerR, Hou Z, Rajagopal N, Ray P, et al.Epigenomic analysis nke multilineage iche nke mmadụ embrayo stem cell.Cell.2013;153: 1134-48 .
17. Li Y, Zheng H, Wang Q, Zhou C, WeiL, Liu X, et al.Nyocha gbasara genome na-ekpughe ọrụ Polycomb na-akwalite hypomethylation nke ndagwurugwu methylation DNA.Genome Bio.2018;19:18 .
18. Koch A, JoostenSC, Feng Z, de Ruijter TC, DrahtMX, MelotteV,
et al.Nyocha nke DNA methylation na ọrịa kansa: ọnọdụ elegharịghachiri.Nat Rev Clin Oncol.2018;15: 459-66 .
19. KleinEA, Richards D, Cohn A, TummalaM, Lapham R, Cosgrove D, et al.Nnwale nchọpụta mmalite nke ọtụtụ ọrịa kansa dabere na methylation ezubere iche site na iji ntọala nkwado nọọrọ onwe ya.Ann Oncol.2021;32: 1167-77 .
20. Hanahan D, Weinberg RA.Ihe ịrịba ama nke ọrịa cancer.Cell.2000;100: 57-70.
21. Hanahan D. Ihe ngosi nke ọrịa cancer: akụkụ ọhụrụ.Ọrịa Cancer Discov.2022;12:31-46 .
22. Schwartzberg L, Kim ES, Liu D, Schrag D. Oncology nke ọma: onye, olee, gịnị, mgbe, na mgbe ọ bụghị?Am Soc Clin Oncol Educ Akwụkwọ.2017: 160-9.
23. Liu H, Meng X, Wang J. Realtime quantitative methylation
nchọpụta nke mkpụrụ ndụ PAX1 na nyocha ọrịa kansa cervical.IntJ Gynecol Cancer.2020;30: 1488-92.
24. Imperiale TF, RansohoffDF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al.Nnwale DNA Multitargetstool maka nyocha ọrịa cancer colorectal.N EnglJ Med.2014;370: 1287-97 .
25. Li J, Li Y, Li W, Luo H, Xi Y, Dong S, et al.Ndokwa nduzi
usoro na-achọpụta usoro methylation DNA na-adịghị mma nke na-agbanwe njirimara cell na netwọk onyunyo nke tumor-immune.Genome
Res.2019;29: 270-80 .
26. Gao Q, LinYP, Li BS, Wang GQ, Dong LQ, Shen BY, et al.Nchọpụta ọrịa cancer na-enweghị atụ site na ikesa usoro DNA methylation na-enweghị cell (THUNDER): mmepe na ọmụmụ nkwado onwe.Ann Oncol.2023;34: 486-95 .
27. Dong S, Li W, Wang L, Hu J, Song Y, Zhang B, et al.Mkpụrụ ndụ ihe nketa metụtara Histone bụ hypermethylated na ọrịa cancer akpa ume yana hypermethylated
HIST1H4F nwere ike ijere as pan-cancer biomarker.Ọrịa Cancer Res.2019;79: 6101-12.
28. HeijnsdijkEA, Wever EM,AuvinenA, Hugosson J, Ciatto S, Nelen V, et al.Mmetụta ndụ dị mma nke nyocha antigen akọwapụtara nke prostate.N EnglJ Med.2012;367: 595-605.
29. LuzakA, Schnell-Inderst P, Bühn S, Mayer-Zitarosa A, Siebert U. Clinical irè nke ọrịa cancer na-enyocha biomarker na-enye dị ka ọrụ ahụike na-akwụ ụgwọ onwe ya: nyochaa nhazi.Euro J Ahụike Ọha.2016;26: 498-505.
30. Dong S, Lu Q,Xu P, Chen L, Duan X, Mao Z, et al.
PCDHGB7 hypermethylated dị ka naanị ihe nrịbama ọrịa kansa zuru ụwa ọnụ yana ngwa ya na nyocha ọrịa kansa cervical n'oge.Clin Transl Med.2021;11: e457.
31. Yuan J, Mao Z, Lu Q,Xu P, Wang C, Xu X, et al.Hypermethylated PCDHGB7 dị ka ihe na-ahụ maka biomarker maka mmalite nchọpụta ọrịa kansa endometrial n'ụdị brush endometrial na scraping cervical.N'ihu Mol Biosci.2022;8: 774215 .
32. Dong S, Yang Z,Xu P, Zheng W, Zhang B, Fu F, et al.N'otu aka
Mgbanwe pụrụ iche epigenetic na SIX6 nwere hypermethylation maka ogbo precancerous na nchọta mpụta metastasis.Ebumnuche Ntugharị Mgbaama Ebe ahụ.2022;7:208.
33. Huang L, Guo Z, Wang F, Fu L. KRAS mutation: si undruggable ka druggable na cancer.Ebumnuche Ntugharị Mgbaama Ebe ahụ.2021;6:386 .
34. Belinsky SA, Nikula KJ, PalmisanoWA, MichelsR, SaccomannoG, GabrielsonE, et al.Aberrant methylation nke p16 (INK4a) bụ ihe omume dị nso na ọrịa cancer akpa ume yana ihe nwere ike ime biomarker maka nchọpụta mmalite.Ụgwọ nke ụlọ ọrụ Proc Natl Acad Sci U SA1998;95: 11891-6.
35. Robertson KD.DNA methylation na ọrịa mmadụ.Nat Rev Genet.2005;6: 597-610.
36. WentzensenN, Walker JL, Gold MA, Smith KM, ZunaRE,
Mathews C, et al.Ọtụtụ biopsies na nchọpụta nke ihe mmalite nke ọrịa cancer cervical na colposcopy.J Clin Oncol.2015;33:83-9.
37. De Strooper LM, Meijer CJ, Berkhof J, Hesselink AT, Snijders
PJ, Steenbergen RD, et al.Nyocha methylation nke FAM19A4
gene in cervical scrapes na-arụ ọrụ nke ọma n'ịchọpụta cervical
carcinomas na ọnya CIN2/3 dị elu.Ọrịa kansa Prev Res (Phila).2014;7: 1251-7 .
38. Thai AA, Solomon BJ, Sequist LV, Gainor JF, Heist RS.Ọrịa cancer akpa ume.Lancet.2021;398: 535-54 .
39. Grunnet M, Sorensen JB.Carcinoembryonic antigen (CEA) dị ka akara akpụ na ọrịa kansa akpa ume.Ọrịa cancer akpa ume.2012;76: 138-43 .
40. Osisi DE, KazerooniEA, Baum SL, EapenGA, EttingerDS, Hou L, et al.Nyochaa ọrịa cancer akpa ume, ụdị 3.2018, NCCN Clinical Practice Guidelines na Oncology.J Natl Compr Canc Netwọk.2018;16: 412-41 .
41. American Cancer Society.Akụkọ gbasara ọrịa kansa na ọnụọgụgụ.Atlanta, GA, USA: American Cancer Society;2023 [emelitere 2023 Maachị 1;zoro aka na 2023 Ọgọst 22].
42. FonthamETH, Wolf AMD, Ụka TR, EtzioniR, Okooko osisi CR,
Herzig A, et al.Nyochaa ọrịa kansa cervical maka ndị mmadụ n'otu n'otu na nkezi ihe egwu: mmelite ntuziaka 2020 sitere na American Cancer Society.CA Cancer J Clin.2020;70: 321-46 .
43. Clarke MA, Long BJ, Del Mar MorilloA, Arbyn M, Bakkum-Gamez JN, Wentzensen N. Association of endometrial cancer ize ndụ na postmenopausal ọbara ọgbụgba na ụmụ nwanyị: a usoro nyochaa na meta- analysis.JAMA Intern Med.2018;178: 1210-22 .
44. Jacobs I, Gentry-Maharaja, Burnell M, ManchandaR, Singh N,
Sharma A, et al.Mmetụta nke transvaginal ultrasound screening
maka ọrịa cancer endometrial na ụmụ nwanyị postmenopausal: ọmụmụ ihe na-achịkwa n'ime otu UKCTOCS.Lancet Oncol.2011;12:38-48 .
45. BabjukM, Burger M, CompératEM, Gontero P, MostafidAH,
PalouJ, et al.European Association of Urology Guidelines on non- muscle-invasive Bladder Bladder Cancer (TaT1 na Carcinoma In Situ) -
Mmelite 2019.Ọnụ ego euro.2019;76: 639-57 .
46. Aragon-Ching JB.Ihe ịma aka na ọganihu na nchoputa, bayoloji, na ọgwụgwọ nke urothelial elu tract na eriri afo carcinomas.Urol Oncol.2017;35: 462-4 .
47. Rizvi S, KhanSA, Hallemeier CL, Kelley RK, Gores GJ.
Cholangiocarcinoma - echiche na-agbanwe agbanwe na usoro ọgwụgwọ.Nat Rev Clin Oncol.2018;15:95-111.
48. Ye Q, Ling S, Zheng S, Xu X. Liquid biopsy in hepatocellular
carcinoma: mkpụrụ ndụ tumor na-ekesa na DNA tumor na-ekesa.Ọrịa cancer Mol.2019;18:114 .
49. Zhang Y, Yao Y, Xu Y, Li L, Gong Y, Zhang K, et al.Pan-cancer
Nchọpụta DNA tumor na-ekesa ihe karịrị ndị ọrịa China 10,000.Nat Commun.2021;12:11 .
50. Eisenhauer EA, Therasse P, BogaertsJ, Schwartz LH, Sargent D, Ford R, et al.Ntụle nyocha nzaghachi ọhụrụ na etuto siri ike: ntuziaka RECIST edegharịrị (ụdị 1.1).Ego J Cancer.2009;45: 228-47 .
51. LitièreS, Colllette S, de Vries EG, Seymour L, BogaertsJ.RECIST - ịmụta site n'oge gara aga iji wuo ọdịnihu.Nat Rev Clin Oncol.
2017;14: 187-92 .
52. Seymour L, BogaertsJ, Perrone A, FordR, Schwartz LH, Mandrekar S, et al.iRECIST: ntuziaka maka njirisi nzaghachi maka ojiji na nnwale
na-anwale immunotherapeutics.Lancet Oncol.2017;18: e143-52 .
53. PantelK, Alix-Panabières C. Liquid biopsy na obere ọrịa fọdụrụnụ - ọganihu ọhụrụ na ihe ọ pụtara maka ọgwụgwọ.Nat Rev Clin Oncol.2019;16: 409-24 .
Kpọtụrụ akụkọ a dị ka: Qian C, Zou X, Li W, Li Y, Yu W. The outpost megide cancer: eluigwe na ala cancer naanị akara.Ọrịa Cancer Biol Med.2023;20: 806-815.
doi: 10.20892/j.issn.2095-3941.2023.0313
Oge nzipu: Mee-07-2024