Amakuru - The outpost kurwanya kanseri: ibimenyetso bya kanseri yisi yose

MINI ISUBIZO

The outpost kurwanya kanseri: ibimenyetso bya kanseri yisi yose

Chengchen Qian1, Xiaolong Zou2, Wei Li1,3, Yinshan Li4, Wenqiang Yu5

1Shanghai Epiprobe Biotechnology Co, Ltd, Shanghai 200233, Ubushinwa;Ishami ry’ubuvuzi rusange, ibitaro bya mbere bishamikiye kuri kaminuza y’ubuvuzi ya Harbin, Harbin 150001, Ubushinwa;3Shandong Epiprobe Medical Laboratory Co., Ltd, Heze 274108, Ubushinwa;Ibitaro byabaturage byakarere ka Ningxia Hui byigenga, kaminuza yubuvuzi ya Ningxia, Yinchuan 750002, Ubushinwa;5Shanghai Health Health Clinical Centre & Ishami ry’Ubuvuzi Rusange, Ibitaro bya Huashan & Kanseri Metastasis Institute & Laboratoire ya RNA Epigenetics, Ibigo by’ubumenyi bw’ibinyabuzima, Ishuri Rikuru ry’Ubuvuzi rya Shanghai, Kaminuza ya Fudan, Shanghai 200032, Ubushinwa

AMASOKO

Kanseri niyo itera impfu nyinshi ku isi.Kumenya hakiri kare kanseri birashobora kugabanya impfu z'ubwoko bwose bwa kanseri;icyakora, biomarkers ikora neza irabura kubwoko bwa kanseri.Methylation ya ADN yamye ari intego nyamukuru yinyungu kuko methylation ya ADN ikunze kubaho mbere yizindi mpinduka zigaragara.Mu gihe hakorwa iperereza ku bintu bisanzwe biranga kanseri ukoresheje uburyo bushya bwo kuyobora urutonde rwa methylation ya ADN, urutonde rwa kanseri ku isi hose (UCOMs) rwagaragaye nk'abakandida bakomeye kugira ngo bamenye neza kanseri hakiri kare kandi neza.Mugihe agaciro kamavuriro ya biomarkers ya kanseri igabanutse kubera sensibilité nkeya na / cyangwa umwihariko muke, ibiranga umwihariko wa UCOMs bitanga ibisubizo bifatika mubuvuzi.Kwemeza ubushobozi bwa kliniki ya UCOMs mu bihaha, inkondo y'umura, endometrale, na kanseri ya urothelia irashigikira kandi ikoreshwa rya UCOM mu bwoko bwa kanseri zitandukanye ndetse no mu mavuriro atandukanye.Mubyukuri, ikoreshwa rya UCOMs kuri ubu ririmo gukorwaho iperereza rikomeye hamwe n’isuzuma ryakozwe mu kumenya hakiri kare kanseri, gusuzuma indwara zifasha, kuvura neza, no gukurikirana inshuro nyinshi.Uburyo bwa molekuline UCOMs itahura kanseri nizo ngingo zikurikira zigomba gukurikiranwa.Ikoreshwa rya UCOMs mubyukuri-isi nayo isaba gushyira mubikorwa no kunonosorwa.

IJAMBO RY'INGENZI

Kumenya kanseri;gusuzuma kanseri;Methylation ya ADN;indwara ya kanseri;kanseri biomarkers

Kuki dukeneye byihutirwa biomarkers?

Nyuma yo kurwanya kanseri mu binyejana birenga ijana, kanseri iracyahungabanya ubuzima bw’ibinyabuzima ku bantu.Kanseri ikomeje guhangayikishwa n'ubuzima ku isi hose hamwe na miliyoni 19.3 n’abantu bashya bangana na miliyoni 10 bapfuye mu 20201. Mu 2020, mu Bushinwa hagaragaye miliyoni 4,6 z’abanduye kanseri, bangana na 23.7% by'abanduye kanseri nshya ku isi nk'uko GLOBOCAN1 ibivuga.Byongeye kandi, impfu zigera kuri miliyoni 3 zatewe na kanseri mu Bushinwa mu 2020, zikaba 30% by'impfu ziterwa na kanseri ku isi1.Iyi mibare yerekanaga ko Ubushinwa buza ku mwanya wa mbere mu kwandura no guhitanwa na kanseri.Byongeye kandi, imyaka 5 yo kubaho kwa kanseri ni 40.5%, ibyo bikaba bikubye inshuro 1.5 ugereranije n’imyaka 5 yo kubaho muri Amerika2,3.Ugereranije ugereranije no kubaho no guhitanwa n’impfu nyinshi mu Bushinwa kuruta mu bihugu bifite ibipimo by’iterambere ry’abantu byerekana ko hakenewe byihutirwa gahunda yo gukumira no kugenzura kanseri ikora neza kandi ihendutse.Kumenya hakiri kare kanseri nikimwe mubintu byingenzi muri sisitemu yubuzima.Kumenya hakiri kare kanseri birashobora kunoza imenyekanisha no kubaho hakiri kare mubwoko bwose bwa kanseri4.Ingamba zo gusuzuma neza zatumye igabanuka rikabije ry’impfu n’impfu za kanseri y'inkondo y'umura, amabere, amabara, na prostate.

Kugirango ugaragaze hakiri kare kanseri, ariko, ntabwo ari ibintu byoroshye.Gukora iperereza ku binyabuzima no guhanura kanseri hakiri kare, kumenya no kwemeza ibinyabuzima byizewe hakiri kare, no guteza imbere ikoranabuhanga ryoroshye kandi ryihuse ryamenyekanye buri gihe byabaye inzitizi zikomeye muri gahunda.Kumenya neza kanseri birashobora gutandukanya ibyiza nibikomere bibi, bifasha kwirinda inzira zidakenewe kandi byorohereza gucunga indwara.Muri iki gihe ingamba zo gutahura hakiri kare zirimo biopies ishingiye kuri endoscope, amashusho yubuvuzi, cytologiya, immunoassays, hamwe nibizamini bya biomarker5-7.Kuba byinjira kandi bihenze, biopies ishingiye kuri endoskopi itwara umutwaro uremereye nkuburyo bukomeye bwubuvuzi bushingiye kubakozi babigize umwuga.Kimwe na cytologiya, uburyo bwombi bwo gusuzuma buterwa ninzobere mubuvuzi kandi bushingiye kubitekerezo byawe bwite hamwe nibikorwa bitari byiza8.Ibinyuranye, immunoassays ntabwo ari yo rwose, urebye ibipimo biri hejuru-byiza.Kwerekana amashusho yubuvuzi, nkuburyo bwo gusuzuma, bisaba ibikoresho bihenze hamwe nabatekinisiye kabuhariwe.Kubwibyo, amashusho yubuvuzi ni make cyane kubera kuboneka bike.Kubera izo mpamvu zose, biomarkers isa nkaho ari uburyo bwiza bwo kumenya kanseri hakiri kare.

Abandikirana: Yinshan Li na Wenqiang Yu

Email: liyinshan@nxrmyy.com and wenqiangyu@fudan.edu.cn

ID ID ORCID: https://orcid.org/0009-0005-3340-6802 na

https://orcid.org/0000-0001-9920-1133

Yakiriwe ku ya 22 Kanama 2023;byemewe ku ya 12 Ukwakira 2023;

byatangajwe ku ya 28 Ugushyingo 2023.

Ushobora kuboneka kuri www.cancerbiomed.org

Inshingano-Ntabwo ari ubucuruzi 4.0 Uruhushya mpuzamahanga

Kugeza ubu ibinyabuzima byashyizwe mu byiciro nka poroteyine, ibimenyetso bya mutation ya ADN, ibimenyetso bya epigenetike, imiterere ya chromosomal, ibimenyetso bya RNA bikomoka ku bibyimba, cyangwa ibice by’ibibyimba byabonetse mu buryo butaziguye biva mu mazi.Ibimenyetso bya poroteyine nibyo biomarkers ikoreshwa cyane mugupima kanseri no gusuzuma.Intungamubiri za poroteyine, nk'isuzuma rya bio- marike, zigarukira ku kuba umuntu ashobora kwibasirwa n'ibikomere byiza, biganisha ku gusuzuma no gukabya gukabije, nk'uko byagaragaye kuri α-fetoproteine na antigen yihariye ya prostate (PSA) 9,10.Ibimenyetso bya RNA birimo imiterere yimiterere yandi moko hamwe nibindi bimenyetso bidafite ibimenyetso bya RNA.Ikomatanyirizo ryerekana imiterere ya genetike Ibimenyetso bya RNA birashobora kumenyekana ukoresheje ingero zinkari, ibyiyumvo byayo bikaba bitari bishimishije (60%) kubyimba byibanze, no kubimenya bishobora bigira ingaruka kumiterere yoroshye yo kwangirika kwa RNA mubidukikije11.Ibimenyetso bya genetike na epigenetike byombi bihura nikibazo cyo kwandura ibibyimba no kugarukira ku bwoko bwa kanseri.

Methylation ya ADN yabaye umukandida ukomeye nka biomarker hakiri kare kuva yatangira gukoreshwa na kanseri na Feinberg mu 198312. Gukuramo methylation ya ADN bigaragara mu byiciro byose bya kanseri, hakiri kare.Aberrant ADN hypermethylation mubisanzwe ibera kubirwa bya CpG mubateza imbere gene kugirango barwanye ibibyimba 13,14.Ubushakashatsi bwerekanye kandi ko hypermethylation ya ADN idasanzwe igira uruhare mu kugenzura ibiyobora iterambere15.Ikibaya cya methylation ya ADN, gikunze guhuzwa nubugenzuzi bwiterambere hamwe na kanseri ya hypermethylated, birashobora guhindura uburyo bwo kwerekana imiterere ya gene muburyo butajegajega bwa ADN methylation kandi bikagabanya guhuza na methylated histone H3K27me3 hamwe na poroteyine za polycomb16,17.

Mu mubare munini wa ADN methylation marike yatangajwe, benshi bagaragaye neza ku isoko;nigute, ibimenyetso bya ADN ya methylation yubucuruzi hamwe nibisuzumwa byo gupima ntibirakingura byimazeyo ubushobozi bwo kumenya kanseri hakiri kare kubwimpamvu nyinshi18.Mugihe ahanini cyerekana imikorere yemewe ukoresheje amakuru yububiko, aba biomarkers mubisanzwe ntibakora neza muburyo busanzwe bitewe nuburyo ibyitegererezo nyabyo bikunze kuba bigoye kandi ntabwo bihagarariwe nkibyatoranijwe mububiko.Ibihe bizakurikiraho-bishingiye kuri kanseri nyinshi methylation yamenyekanye hakiri kare byagaragaye ko bifite 16.8% na 40.4% gusa muri kanseri yo mu cyiciro cya I na II.Ibizamini byo gutahura hakiri kare bisaba gutuza cyane hamwe na biomarkers neza.

Kanseri yisi yose yerekana gusa (UCOM) kuvumbura ukoresheje icyerekezo gikurikirana (GPS)

Nubwo hashize imyaka ibarirwa muri za mirongo ubushakashatsi bwa kanseri, kwirinda no kuvura bishimishije ntibyagerwaho.Uburyo bushya burakenewe kugirango abashakashatsi basuzume neza kanseri.Mu myaka 23 ishize, ibimenyetso 6 bya kanseri, nko kwirinda apoptose, gutera tissue & metastasis, nibindi, byaraguwe bigera kuri 14 hashyizwemo ibintu nka porogaramu zidasanzwe za porogaramu zidasanzwe hamwe na mikorobe ya polymorphique20,21.Mugihe amakuru arambuye yerekeye kanseri ashyizwe ahagaragara, abantu benshi binjira mu bushakashatsi bwa kanseri.Ubushakashatsi bwa kanseri bwagiye buhoro buhoro muri newera mu byerekezo bibiri (guhuza no kugiti cye).Hamwe n’iterambere rya onkolojiya yuzuye mu myaka yashize, ubushakashatsi bwibanze kuri kanseri bushingiye ku buvuzi bwihariye bwihariye hamwe na kanseri itandukanye.Niyo mpamvu, ibimenyetso bya kanseri biherutse kumenyekana byibanze cyane cyane ku bwoko bwa kanseri, nka kanseri y’indwara ya PAX6 na BMP3 kuri kanseri yibara 24.Imikorere yibi biyomarki yihariye ubwoko bwa kanseri iratandukanye, ariko biracyashoboka ko abantu banduye bashobora kwipimisha kanseri icyarimwe icyarimwe kubera kugabanuka kwicyitegererezo cyibinyabuzima hamwe nigiciro kinini.Byaba byiza turamutse tumenye biomarker imwe, ikomeye ikora kanseri yubwoko bwose mugihe cyambere.

Kugirango ugere ku ntego nziza, umukandida mwiza wa biomarker agomba gutoranywa kurutonde rwubwoko bwa biomarker.Gukuramo methylation ya ADN, mubisobanuro byose byerekeranye na genetique na epige- netic, bizwi ko bifitanye isano na kanseri kandi ni bimwe mubya mbere, niba atari ubwa mbere, ibintu bidasanzwe biterwa na kanseri bibaho bikurikiranye.Iperereza rya methylation ya ADN ryatangiye hakiri kare, ariko ryabujijwe no kubura uburyo bwubushakashatsi.Muri miliyoni 28 zishobora gukoreshwa methylated CpG muri genome, umubare ushobora gucungwa ugomba gutahurwa ugahuzwa na genome kugirango wumve neza tumorigenez.Gukurikirana genome bisulfite yose (WGBS), ifatwa nkigipimo cyizahabu cya methylation ya ADN ikurikirana, irashobora gukwirakwiza 50% ya Cs mungirangingo ya kanseri bitewe nuburyo bwo kuvura bisulfite buvuna ibice bya ADN kandi bikagabanya ingirabuzimafatizo za genome mugihe guhinduka kwa Cs-kuri-Ts25.Ubundi buryo, nka chipi 450k, bikubiyemo gusa 1,6% ya methylation ya genome.Ukurikije amakuru ya 450k, akanama gashinzwe kumenya methylation ya ADN gafite 35.4% ibyiyumvo byubwoko 6 bwa kanseri ya kanseri26.Imipaka yubwoko bwa kanseri, imikorere mibi, n urusaku biterwa nuburyo bwo gutahura mugikorwa cyo gusesengura byabaye inzitizi zikomeye kumpande zerekana kanseri.

Kugira ngo turusheho gukora iperereza ku buryo bwa epigenetike ya selile mugihe cya tumorigenez na metastasis, twashyizeho GPS idasanzwe yo kumenya ADN methylation ya genome yagutse, igera kuri 96% byimbuga za CpG muri miliyari 0.4 zasomwe25.GPS nuburyo bukurikirana muburyo bubiri ukoresheje 3 ′ iherezo rya ADN igice cya methyl-cytosine idahinduka nyuma yo kuvura bisulfite iyobora guhuza imibare ya methylation ya ADN ya 5 ′ iherezo ikoresheje ikurikiranwa ryombi (Ishusho 1) 25.Methyl-cytosine iyobora umurongo, ikora nk'icyitegererezo, ifasha mukarere ka GC ihuza cyane igarura amakuru yakurikiranwe cyane muri WGBS gakondo.Ikirangantego kinini cya GPS gitanga amakuru menshi ya methylation ya ADN, adufasha gusuzuma imyirondoro ya methylation ya kanseri hamwe n’ibisubizo bihanitse cyane mu turere twakorewe iperereza mbere.

GPS iduha igikoresho gikomeye cyo gukora ubushakashatsi kuri homogeneite ya kanseri, ishobora koroshya cyane ubushakashatsi bwa kanseri kandi ikaba ishobora kubona ibisobanuro rusange kuri tum- origenezi na metastasis.Mugihe cyo gusesengura amakuru ya GPS yumurongo wa kanseri, ibintu bidasanzwe byakunze kugaragara.Hariho uturere twinshi twasaga nkaho hypermethylated idasanzwe muburyo butandukanye bwa kanseri.Ubu bushakashatsi butunguranye bwaje kwemezwa gukora nka UCOMs.Hasesenguwe ingero zirenga 7,000 ziva mu bwoko 17 bwa kanseri ziri mu bubiko bwa Kanseri Genome Atlas (TCGA), muri zo twerekanye UCOM ya mbere, HIST1H4F, gene ijyanye na histone ikaba hypermethylée mu bwoko bwose bwa kanseri27.Urukurikirane rwa UCOM rwabonetse hanyuma rwemezwa mububiko bwa TCGA, ububiko bwa Gene Expression Omnibus (GEO), hamwe nubuvuzi bwukuri bwisi.Kugeza ubu, HIST1H4F, PCDHGB7, na SIX6 zabonetse kandi zemewe nka UCOM.Ubuvumbuzi butunguranye bwa UCOM butanga igisubizo gikomeye kubikenewe kumenya kanseri hakiri kare.UCOMs itanga igisubizo kubimenyetso bimwe byerekana kanseri nyinshi.

Ibiranga UCOM

Bimaze kwemezwa, UCOMs yerekanwe kwerekana ibintu bine byingenzi biranga UCOM kurenga ku mikorere y’ibinyabuzima biriho ubu (Ishusho 2).

Umwihariko mubi

UCOMs yihariye ibisebe bya kanseri cyangwa mbere ya kanseri kandi ntabwo bigira ingaruka kumihindagurikire isanzwe.Bimwe mubimenyetso byerekeranye na kanseri byubu byakoreshejwe cyane mugutahura hakiri kare no / cyangwa kwipimisha byatumye habaho kwisuzumisha birenze.Urwego rwo hejuru rwa PSA, igikoresho cyo gusuzuma cyemewe na clinique, nacyo kigaragara mubihe byiza, nka prostate hyperplasia na prostatite10.Kwipimisha birenze urugero no kuvurwa birenze urugero bituma ubuzima bugabanuka bitewe ninda, inkari, nibibazo byimibonano mpuzabitsina28.Ibindi bishingiye kuri poroteyine kandi bikoreshwa cyane na biomarkers mu mavuriro, nka CA-125, nta nyungu nini byatanze mu gihe cyo kwisuzumisha birenze urugero no gukabya 29.Umwihariko wo hejuru wa UCOM kuri malignancies wirinda izi ngufi.UCOM, PCDHGB7, itandukanya neza ibikomere byo mu rwego rwo hejuru byo mu nda (HSILs) na kanseri y'inkondo y'umura biturutse ku ngero zisanzwe hamwe no mu cyiciro cyo hasi cyo mu bwoko bwa squa- mous intraepithelial lesion (LSILs), mu gihe ibindi bimenyetso byinshi bishobora gutandukanya kanseri y'inkondo y'umura n'ibisanzwe bisanzwe30.Nubwo PCDHGB7 itagaragaza itandukaniro rinini hagati ya endometrium isanzwe na hyperplasia ya endometrale, itandukaniro rikomeye rigaragara hagati ya endometrium ya nor- mal na hyperplasia idasanzwe, ndetse n’itandukaniro rinini rigaragara hagati ya endometrium isanzwe na kanseri ya endometrale (EC) ishingiye kuri PCDHGB731.UCOMs yihariye ibikomere bibi mububiko no mubitaro byubuvuzi.Ukurikije uko umurwayi abibona, UCOM idasanzwe igabanya urwego rwo gusobanukirwa ibimenyetso byerekana ibimenyetso bitandukanye byerekana imikorere mibi ya biomarkers idahwitse hamwe nimpungenge zijyanye nigihe cyo gusuzuma.Dukurikije uko clinique ibibona, UCOM idasanzwe itandukanya indwara mbi n’indwara zangiza, zifasha mu cyiciro cy’abarwayi kandi bikagabanya uburyo bwo kwivuza bitari ngombwa no gukabya.Kubwibyo, UCOM idasanzwe igabanya sisitemu yubuvuzi, kugabanya ibibazo bya sisitemu, no gutanga ibikoresho byinshi byubuvuzi kubakeneye.

Igishushanyo 1 Igishushanyo mbonera cya GPS yo gukora ADN methylation detection25.Umurongo wijimye: kwinjiza ADN ikurikiranye;umurongo utukura: ADN ivurwa na T4 ADN polymerase, isimbuza cytosine na 5′-methylcytosine kuri 3 ′ iherezo ryinjiza;ubururu C hamwe nanjye: methylated cytosine;ubururu C: cytosine idafite methylated;umuhondo T: thymine25.

Byose cyangwa ntacyo

UCOM iboneka gusa mu ngirabuzimafatizo za kanseri kandi igaragara neza mu ngirabuzimafatizo hafi ya zose.HIST1H4F yemejwe kuba hypermethylated hafi yubwoko bwose bwibibyimba ariko ntabwo biri mubitegererezo bisanzwe27.Mu buryo nk'ubwo, PCDHGB7 na SIX6 nazo zagaragaye ko ari hypermethylated mu byitegererezo byose by’ibibyimba ariko bitari mu ngero zisanzwe30-32.Ibi bidasanzwe biranga kunoza imikorere ya UCOMs kubijyanye nimipaka yo gutahura no kumva.Nka 2% by'utugingo ngengabuzima twa kanseri dushobora gutandukanywa mu ngero, bigatuma UCOMs iba biomarker yunvikana cyane kuruta biomarkers iriho30.Nkuko biomarker ikoreshwa mugutahura kanseri yibara, ihinduka rya KRAS ribaho gusa hafi 36% byabanduye kanseri yibara, gutanga ibitekerezo byubushobozi buke bwo gusuzuma33.Umubare muke wa mutation ya KRAS muri kanseri yibara igabanya KRAS hamwe nibindi binyabuzima.Mubyukuri, guhuza biomarkers birasa nkibyiringiro muburyo bwambere, ariko ntabwo buri gihe bitanga umusaruro ushimishije mugihe werekana urusaku rwinshi mugusesengura gutahura kandi mubisanzwe bikubiyemo uburyo bugoye bwo kugerageza.Ibinyuranye, PCDHGB7 nizindi UCOM zibaho muri kanseri zose.UCOMs igaragaza ibice bya kanseri muburyo butandukanye bwa kanseri yerekana neza neza mugihe ikuraho inzira zisesengura urusaku.Ntabwo bigoye kumenya kanseri murugero rwinshi, ariko biragoye cyane kumenya kanseri murugero ruto.UCOMs irashobora kumenya kanseri nkeya.

Igishushanyo 2 Ibiranga UCOM.

Kumenya kanseri ibanziriza impinduka zindwara

UCOMs irashobora kugaragara mugice kibanziriza kanseri mbere yimpinduka zindwara.Nka epigenetike biomarkers, UCOM idasanzwe ibaho mugihe cyambere kuruta fenotipiki idasanzwe kandi irashobora kugaragara muri tumorigenez, gutera imbere, na metastasis 34,35.Ubukangurambaga bwa UCOM mugihe cyongera imikorere ya UCOM mugutahura kanseri yo hambere hamwe nibisebe mbere ya kanseri.Kumenya kanseri hakiri kare ishingiye kuri biopsies na cytologiya birashobora kugorana naba psychologue babimenyereye.Biopsy imwe yabonetse hakoreshejwe colposcopi yavuzwe ko ari nziza muri 60,6% by'icyitegererezo cya HSIL +.Biopsies yinyongera irakenewe kugirango ibikomere byinshi byongere sensibilité36.Ibinyuranye, UCOM, PCDHGB7, ifite sensibilité ya 82% kuburugero rwa HSIL +, irenze ibyiyumvo bya biopsies na biomarkers30.Ikimenyetso cya methylation, FAM19A4, gifite sensibilité ya 69% kuri CIN2 +, isa na cytologiya, ariko ntishobora gutandukanya CIN1 nicyitegererezo gisanzwe37.UCOMs yerekanwe kuba yunvikana cyane biomarker.Ugereranije n’abahanga mu bumenyi bw'indwara zishingiye ku bumenyi, UCOM zifite ubushobozi bwo kumenya neza kanseri yo hambere, ari nazo zigira uruhare mu kumenyekanisha kanseri no kubaho30.Byongeye kandi, UCOMs itanga urubuga rwo gutahura rushobora kugera kubice bidafite abahanga mu bumenyi bw'indwara kandi bitezimbere cyane.Hamwe nuburyo bumwe bwo gutoranya no gutahura, gutahura UCOM bitanga ibisubizo bihamye kandi byoroshye-gusobanura ibisubizo bihuye neza na protocole yo gusuzuma isaba abakozi babigize umwuga hamwe nubuvuzi.

Kumenya byoroshye

Uburyo bugezweho bwo kumenya methylation ya ADN buragoye kandi butwara igihe.Byinshi muburyo busaba guhinduka kwa bisulfite, bitera igihombo mubwiza bw'icyitegererezo kandi birashoboka ko bitanga ibisubizo bitajegajega kandi bidahwitse.Imyororokere mibi iterwa no kuvura bisulfite irashobora gutera urujijo kubaganga n’abarwayi kandi bikabangamira ingamba zo gukurikirana no / cyangwa kuvura.Kubwibyo, twongeye guhindura uburyo bwo kumenya UCOM kugirango twirinde kuvura bisulfite iteye ibibazo byintangarugero, byujuje ibisabwa kwa muganga, kandi tunoze uburyo bworoshye.Twateje imbere uburyo bushya dukoresheje imisemburo ya methylation-itabuza guhuza imisemburo ifatanije nigihe nyacyo cya fluorescent PCR (Me-qPCR) kugirango tumenye methylation ya UCOMs mugihe cya 3 h dukoresheje uburyo bworoshye bwo gukora (Ishusho 3).Me-qPCR irashobora kwakira ubwoko butandukanye bw'icyitegererezo, nk'ikusanyirizo ry'amavuriro y'ibicurane by'umubiri hamwe n'inkari zegeranijwe.Ingero zamavuriro zegeranijwe zirashobora gutunganywa, kubikwa, kandi byoroshye gutahura hakoreshejwe gukuramo ADN isanzwe kandi yikora.ADN yakuweho irashobora gukoreshwa muburyo butaziguye kuri Me-qPCR kugirango habeho inkono imwe hamwe nibisubizo byatanzwe.Nyuma yisesengura ryibisubizo byoroshye ukoresheje uburyo bwo gusuzuma bwashyizweho kandi bwemejwe kubwoko bwa kanseri bwihariye, icyemezo cya nyuma cyibisubizo bya UCOM cyasobanuwe kandi gitangwa nkigiciro cyinshi.Ihuriro rya Me-qPCR rirenze bisulfite-pyrosequensiya gakondo mu gutahura UCOM mu gihe uzigama 3 h ya bisulfite, nk'uko bivugwa na EZ ADN Methylation-Gold kit protocole.Uburyo bushya bwa methylation detection butuma UCOM itahura neza, neza, kandi ikaboneka30.

Igishushanyo 3 Uburyo bwo kumenya UCOM.Ubwoko bw'icyitegererezo burimo ubuhanga bwa BALF, Pap brush, na / cyangwa inkari zegeranijwe.Uburyo bwo gukuramo ADN bushobora kwakirwa mu buryo bwikora, ibicuruzwa bishobora gutahurwa na qPCR.

Ikoreshwa rya UCOM

Kanseri y'ibihaha

Kanseri y'ibihaha ni kanseri ya kabiri ikunze kugaragara cyane kandi yica abantu benshi ku isi, bangana na 11.4% by'abanduye na 18.0% by'impfu nshya1.Mu kwisuzumisha byose, 85% ni kanseri y'ibihaha itari ntoya (NSCLC) naho 15% ni kanseri y'ibihaha ntoya (SCLC), ifite urwego rwo hejuru rwa malignance38.Gusikana ibipimo bike bya tomografiya (LDCT) ni uburyo busabwa bwo gusuzuma kanseri y'ibihaha kandi byagaragaye ko byanoza hakiri kare no kugabanya impfu6;icyakora, kubera umwihariko muke no kutagerwaho neza, LDCT itarakora nkuburyo bushimishije bwo gusuzuma, kimwe nibindi bimenyetso bya kanseri bisanzwe, nka CEA39.Ibiciro hamwe nibishoboka byo kwisuzumisha no gusuzuma nabi ingamba zo gusuzuma LDCT bibangamira iterambere rya kanseri y'ibihaha yo kuzamura40.HIST1H4F, UCOM, ifite imbaraga nini nka biomarker hakiri kare mumazi ya bronchoalveolar fluid (BALF) 27.HIST1H4F ni hypermethylated muri adenocar- cinoma no mu bihaha squamous selile carcinoma, ifite umwihariko wa 96.7% hamwe na sensibilité ya 87.0% (Ishusho 4A), kandi imikorere idasanzwe ya kanseri yo mu cyiciro cya 27.HIST1H4F ifite umwihariko wa 96.5% hamwe na sensibilité ya 85.4% kuri NSCLC, na 96.5% na 95.7%, kuri SCLC27.Byongeye kandi, ingero z’ubundi bwoko umunani bwa kanseri, harimo kanseri ya pancre- atic na kanseri yu mura, zemeje ko HIST1H4F ari hypermethylated mu bwoko umunani27.

Kanseri y'inkondo y'umura

Kanseri y'inkondo y'umura yari kanseri ya kane ikunze kugaragara cyane kandi ikaba iya kane mu bitera impfu za kanseri ku bagore mu 2020, bangana na 3.1% by'abanduye na 3,4% by'impfu ziterwa na kanseri ku isi1.Kurandura kanseri y'inkondo y'umura mu 2030, nk'uko byasabwe na OMS, ni ngombwa kumenya hakiri kare kanseri y'inkondo y'umura.Iyo bigaragaye hakiri kare, imyaka 5 yo kubaho igera kuri 92% hamwe na kanseri y'inkondo y'umura itera 41.Amabwiriza ya Sosiyete y'Abanyamerika ya Kanseri (ACS) yerekana ibizamini bya cytologiya y'inkondo y'umura, ibizamini bya HPV by'ibanze, cyangwa coteste yo gusuzuma42.Indwara ya nyababyeyi itera kandi irashobora kumenya 63.5% gusa ya CIN2 +.

PCDHGB7, bitandukanye, yakoze neza cyane ikoresheje Pap smears hamwe nudusabo twigitsina, kandi irashobora gutandukanya HSIL na LSIL muburyo bukabije.PCDHGB7 yonyine ifite sensibilité ya 100.0% kandi umwihariko wa 88.7% kuri kanseri y'inkondo y'umura (Igicapo 4B), hamwe na 82.1% ibyiyumvo na 88.7% byihariye kuri HSIL + ingero30.PCDHGB7 ifite kandi ibyiyumvo bya 90.9% hamwe na 90.4% byihariye mubisubizo by'inda ibyara kanseri y'inkondo y'umura, byoroshye gukusanya30.Iyo uhujwe n’ikizamini kinini (hr) HPV cyangwa Ikizamini cya Thinprep Cytology (TCT), PCDHGB7 yiyongereyeho sensibilité ya 95.7% kandi yihariye ya 96.2%, irenga cyane ikizamini cya hrHPV (20.3%), TCT (51.2%) ), hamwe byombi hamwe (57.8%) kuri kanseri y'inkondo y'umura30.PCDHGB7 yerekanwe kandi kuba hypermethylated mubwoko 17 bwa kanseri uhereye kububiko bwa TCGA, byerekana ko ikwiye mumuryango wa UCOM30.

Igicapo 4 UCOMs zemejwe muburyo bune bwa kanseri mubushakashatsi bunini bwamavuriro.A. Imikorere ya HIST1H4F, UCOM, mugutahura kanseri y'ibihaha ingero 508.B. Imikorere ya PCDHGB7, UCOM, mugutahura kanseri y'inkondo y'umura ingero 844.C. Imikorere ya PCDHGB7, UCOM, mugushakisha kanseri ya endometrale ya 577 Pap na Tao brush.D. Imikorere ya SIX6, UCOM, mugutahura kanseri ya urothelia ingero 177.

EC ni imwe mu kanseri y’imyororokere ikunze kugaragara ku isi, aho abantu bagera kuri miliyoni 4.2 banduye na 1% bapfa bazize kanseri buri mwaka1.Hamwe no kwisuzumisha neza mugihe cyambere, EC irakira kandi ifite imyaka 5 yo kubaho kwa 95% kuri kanseri yo mucyiciro cya mbere.Abarwayi bafite ibimenyetso, nko kuva amaraso munda adasanzwe, bahabwa isuzuma rya buri gihe kandi bagahabwa uburyo bwa biopsy butera kandi bubabaza, nubwo 5% - 10% gusa byaje gutera EC43.Transvaginal ultra- majwi, nkuburyo busanzwe bwo gutahura, ntabwo yizewe cyane kuberako idashobora gutandukanya ibyiza nimpinduka mbi ziterwa nimpinduka mbi hamwe nigipimo kinini cyibinyoma-byiza44.

Ikigereranyo kibangikanye na serumu CA-125, cyakozwe cyane na biomarker ya EC, na PCDHGB7.Serumu CA-125 yari ifite sensibilité ya 24.8%, ibyo bikaba byerekana ko CA-125 ari ikimenyetso kidahagije kuri EC nubwo cyihariye cya 92.3% 31.Gutahura PCDHGB7 ukoresheje icyitegererezo cya Pap brush byatanze umusemburo wa 80.65% kandi umwihariko wa 82.81% mubyiciro bya ECatall, mugihe icyuma cya Tao cyari gifite sensibilité ya 61.29% kandi cyihariye cya 95.31% 31.Icyitegererezo cyo gusuzuma PCDHGB7, gishingiye kuri Me-qPCR, cyatanze sensibilité ya 98.61%, umwihariko wa 60.5%, kandi muri rusange ni 85.5%, ukoresheje icyitegererezo cya Pap na Tao (Ishusho 4C) 31.

Kanseri ya Urothelia

Kanseri ya Urothelia, igizwe n'uruhago, impyiko, na kanseri ya ure-, ni yo kanseri ya karindwi ikunze kugaragara cyane mu mwaka wa 2020 ku isi, itera 5.2% by'abanduye na 3,9% by'impfu1.Kanseri ya Urothelia, irenga 50% muri yo ikaba ari kanseri y'uruhago, ni yo ya kane ya kanseri ikunze kugaragara muri Amerika mu 2022, ikaba 11,6% by'abanduye vuba3.Hafi ya 75% ya kanseri y'uruhago ishyirwa mu rwego rwa kanseri y'uruhago idatera imitsi igarukira kuri mucosa cyangwa subucosa45.Biopsy ya cystoskopi nigipimo cya zahabu mugupima kanseri ya urothelia ishyirwa mubikorwa na fluorescence mugihe cyo kuvanga (FISH) no gupima cytologiya.AMAFI na cytologiya bifite imikorere mibi yo kwisuzumisha, kandi cystoskopi irinjira kandi ifite ibyago byingenzi byo kubura mikorobe, gusobanura nabi ibikomere, kandi bishobora gutera kanseri ikwirakwizwa cyangwa ikongera.UCOM yemewe mbere, PCDHGB7, yerekanwe kandi kuba hypermethylated muri kanseri ya urothelia, ifite agace kari munsi ya 0.86, byerekana ko hashobora kubaho ubushobozi bwo kwisuzumisha30.Kugirango turusheho kwemeza UCOM nyinshi no kwakira neza ubwoko bwikitegererezo, SIX6, igitabo cyitwa UCOM, yarasuzumwe kandi yerekana ubushobozi bwiza bwo kwisuzumisha mugutahura hakiri kare kanseri yinkari ikoresheje urugero rwinkari kurubuga rwa Me-qPCR.Gutahura SIX6 ukoresheje ingero z'inkari byagaragaje ko irushanwa rya 86.7% kandi ryihariye rya 90.8% (Igicapo 4D), mugihe ridatera kandi ryoroshye kubona32.Ubushobozi bwa SIX6 mugukurikirana metastasis no gusuzuma imikorere yubuvuzi burimo gukorwaho iperereza.

Ejo hazaza n'ibibazo

UCOMs ifite imikorere ikomeye mugusuzuma kanseri nyinshi, ariko haracyari byinshi byo gukora.Twagiye twagura urutonde rwa UCOM kandi twakomeje kwemeza UCOM muburyo bwinshi bwa kanseri, harimo izisanzwe zigoye kuyimenya.Kwemeza ibisubizo bivuye mububiko bwa TCGA byongeye gushimangira ikoreshwa rya UCOMs muburyo bwinshi bwa kanseri nibindi bihe.Mu iperereza ryibanze, UCOMs zerekanye ko zifite ubushobozi bwo gusuzuma indwara ya cholangiocarcinoma na pancreatic adenocarcinoma, ibyo bikaba bidashoboka ko umuntu yipimisha mu cyiciro cya mbere hakoreshejwe uburyo bwo gusuzuma 32,47.Ubushobozi bwo kumenya kanseri idasanzwe hamwe na UCOMs burashobora gukoreshwa hamwe no kuzenguruka ibibyimba ADN (ctDNA) hamwe na platform ya biopsy yamazi meza.Ubushakashatsi bwakozwe na plasma ADN ishingiye kuri pan-kanseri yerekana kanseri byatanze sensibilité ya 57.9% 49.Nuburyo bwihariye, imikorere rusange irerekana ko hakiriho iterambere.

Ibiranga UCOMs byihariye kandi byashyigikiye iperereza ryubushobozi bwa UCOM mugusuzuma imikorere yubuvuzi no kugenzura inshuro nyinshi.Dukurikije ibipimo ngenderwaho bisubizwa mu bisubizo bikomeye (RECIST), amashusho y’ubuvuzi ni bwo buryo bwasabwe bwo kugenzura inshuro nyinshi no gusuzuma ingaruka zifatika, mu gihe ibimenyetso by’ibibyimba bikoreshwa byonyine kugira ngo bisuzumwe50.Mubyukuri, icyakora, uburyo bwo gufata amashusho bugira ingaruka cyane kubihe nigihe, bityo bigatuma abarwayi bagira ibyago byinshi nibiciro 51,52.SIX6 yemejwe kugirango ibe intandaro ya kanseri y'ibere metastasis32.Igenzura rya biopsy rishingiye kuri ctDNA ituma hakurikiranwa igihe nyacyo ku ndwara nkeya zisigaye mbere y’amezi mbere yo gutahura radiologique, bikaba byiza bidindiza kandi bikarinda kanseri iterwa no kongera kwiyongera53.Ibisubizo byibanze byerekana ko UCOMs igaragaza urwego rwa hypermethylation ya kanseri mugihe nyacyo nyuma yo kubagwa no kuvurwa32.Ubukangurambaga bukabije bwerekanwa na UCOMs hamwe nuburyo bukoreshwa muburyo butandukanye butabangamirwa butuma UCOM ikora nk'ibisubirwamo byerekana neza biomarker mugihe ikomeza kubahiriza abarwayi.

Mugihe kimwe, uburyo rusange bwo kugera kubizamini nikindi kibazo gikomeye gisaba imbaraga zinyongera.Mugihe ubufatanye bwa UCOM bwakiriwe mubitaro byinshi twizeye ko bizagirira akamaro abarwayi benshi, gutahura pro bono no kwipimisha byakorewe mubikorwa byicyaro mubushinwa.UCOMs isaba uburyo bworoshye bwo kwemererwa kwemererwa nkigikoresho gishoboka cyo gusuzuma, cyane cyane kubice bidateye imbere.

Mugihe porogaramu ya UCOM ibisubizo mugutahura hakiri kare iratanga ikizere, byinshi bitazwi kuri UCOM birahari.Hamwe nubushakashatsi bugaragara, ubushakashatsi bwiyongereye buremewe kubwimpamvu UCOM igaragara kwisi yose muri kanseri.Uburyo bukoreshwa na epigenetike igenga UCOMs bukwiye gukorwaho iperereza, rishobora kwerekana icyerekezo gishya cyo kuvura kanseri.Tugarutse ku mikoranire iri hagati y’ibibyimba biterwa no gutandukana, twishimiye impamvu UCOMs ishobora kuba idasanzwe kuri benshi mu bimenyetso bya kanseri bifitanye isano rya bugufi n'ubwoko bwa kanseri.Uruhare rwa UCOM rwagaragajwe na methylation ya ADN muri tumorigenez, gutera ibibyimba, na metastasis ntirwamenyekanye mugihe cyo gutakaza no kugarura indangamuntu kandi bisaba ko hakorwa igenzura ryimbitse.Iyindi nyungu nyamukuru iri murwego rwo kwinjiza imiterere yuburinganire bwa UCOMs hamwe nuduce twihariye twizeye ko tuzageraho tumenye neza ibimenyetso bya kanseri no kumenya inkomoko yibibyimba muburyo butandukanye.UCOM irashobora kuba igikoresho cyiza cyo gukumira kanseri, kumenya kanseri, no kurinda no gukuraho kanseri.

Tanga inkunga

Uyu murimo washyigikiwe na gahunda y’ingenzi y’igihugu R&D y’Ubushinwa (Impano No 2022BEG01003), Fondasiyo y’igihugu y’ubumenyi bw’ibinyabuzima mu Bushinwa (Impano nimero 32270645 na 32000505), Inkunga yatanzwe na komisiyo ishinzwe ubuzima mu ntara ya Heilongjiang (Impano No 2020-111) , n'inkunga yatanzwe na Heze Science and Technology Institute (Impano No 2021KJPT07).

Amakimbirane yinyungu

Wei Li ni Umuyobozi wa R&D muri Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu akora mu Nama Ngishwanama ya Siyanse ya Epiprobe.W. Yu na Epiprobe bemeje patenti zitegereje zijyanye n'iki gikorwa.Abandi banditsi bose batangaza ko nta nyungu zirushanwa.

Umusanzu w'abanditsi

Gutekereza no gutegura umushinga: Chengchen Qian na Wenqiang Yu.

Andika impapuro: Chengchen Qian.

Yakoze amashusho: Chengchen Qian.

Yasuzumye kandi ahindura inyandiko yandikishijwe intoki: Xiaolong Zou, Wei Li, Yinshan Li na Wenqiang Yu.

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doi: 10.20892 / j.issn.2095-3941.2023.0313

Igihe cyo kohereza: Gicurasi-07-2024