Wararka - Ka-hortagga kansarka: kansarka caalamiga ah oo keliya calaamadaha

MINI DIB U EEGID

Xarunta ka-hortagga kansarka: kansarka caalamiga ah oo keliya calaamadaha

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

1Shanghai Epiprobe Biotechnology Co., Ltd, Shanghai 200233, Shiinaha;2 Qaybta Qalliinka Guud, Cusbitaalka ugu horreeya ee ku xidhan Jaamacadda Caafimaadka ee Harbin, Harbin 150001, Shiinaha;3Shandong Epiprobe Laboratory Medical Co., Ltd, Heze 274108, Shiinaha;4 Isbitaalka Dadka ee Gobolka Ningxia Hui, Jaamacadda Caafimaadka ee Ningxia, Yinchuan 750002, Shiinaha;5Shanghai Public Health Clinical Center & Department of General Surgery, Huashan Hospital & Kansarka Metastasis Institute & Shaybaadhka RNA Epigenetics, Machadyada Sayniska Biomedical, Shanghai Medical College, Fudan University, Shanghai 200032, Shiinaha

MAQAN

Kansarku waa sababta ugu badan ee dhimashada adduunka oo dhan.Ogaanshaha hore ee kansarku wuxuu hoos u dhigi karaa dhimashada dhammaan noocyada kansarka;si kastaba ha ahaatee, biomarkers hore ee wax ku ool ah ayaa ka maqan inta badan noocyada kansarka.Methylation DNA had iyo jeer waxay ahayd bartilmaameed weyn oo xiiso leh sababtoo ah methyl DNA-da waxay badanaa dhacdaa ka hor isbeddelada kale ee hidde-raaca ee la ogaan karo.Iyadoo la baarayo astaamaha caanka ah ee kansarka iyadoo la adeegsanayo hage cusub oo meelaynta isku xigxiga DNA methylation, taxane kansar caalami ah oo keliya (UCOMs) ayaa u soo baxay musharraxiin xooggan oo loogu talagalay ogaanshaha hore ee saxda ah ee saxda ah ee kansarka.Iyadoo qiimaha kiliinikada ee biomarkers kansarka hadda uu hoos u dhaco dareenka hoose iyo / ama gaar ahaan hoose, sifooyinka gaarka ah ee UCOM-yadu waxay xaqiijinayaan natiijooyinka caafimaad ahaan.Xaqiijinta kartida bukaan-socodka ee UCOM-yada sambabada, ilmo-galeenka, endometrial, iyo kansarka urothelial waxay sii taageertaa codsiga UCOM-yada noocyo badan oo kansar ah iyo xaalado caafimaad oo kala duwan.Dhab ahaantii, codsiyada UCOM-yada ayaa hadda ku socda baaritaan firfircoon oo leh qiimeyn dheeraad ah oo lagu ogaanayo hore ee kansarka, ogaanshaha kaaliyaha, waxtarka daaweynta, iyo kormeerka soo noqoshada.Hababka molecular ee ay UCOM-yadu ku ogaadaan kansarrada ayaa ah mawduucyada muhiimka ah ee soo socda ee la baarayo.Codsiga UCOM-yada ee xaaladaha-dhabta ah waxay sidoo kale u baahan tahay hirgelinta iyo hagaajinta.

ERAYADA MUHIIMKA AH

Ogaanshaha kansarka;baaritaanka kansarka;Methylation DNA;kansarka epigenetics;biomarkers kansarka

Waa maxay sababta aan degdeg ugu baahanahay cusub biomarkers?

Ka dib markii la dagaalantay kansarka muddo ka badan qarni, kansarku wali waa halista bayooloji ee ugu halista badan aadanaha.Kansarka ayaa weli ah walaac caafimaad oo caalami ah iyadoo 19.3 milyan oo xaaladood oo cusub ah iyo ku dhawaad 10 milyan oo dhimasho lagu qiyaasay 20201. 2020 ayaa lagu qiyaasay 4.6 milyan oo xaaladood oo cusub oo kansar ah ayaa laga helay Shiinaha, taasoo ka dhigan 23.7% kiisaska cusub ee kansarka adduunka sida ay sheegtay GLOBOCAN1.Intaa waxaa dheer, ku dhawaad 3 milyan oo dhimasho ah ayaa loo aaneeyay kansarka Shiinaha sanadka 2020, kuwaas oo ahaa 30% dhimashada la xiriirta kansarka adduunka1.Tirakoobyadani waxay muujiyeen in Shiinuhu uu kaalinta koowaad kaga jiro dhacdooyinka iyo heerka dhimashada kansarka.Waxaa intaa dheer, heerka badbaadada kansarka ee 5-ta sano waa 40.5%, taas oo 1.5 jeer ka hooseysa heerka badbaadada 5-sano ee Mareykanka2,3.Isbarbardhigga badbaadada hooseeya iyo heerka dhimashada sare ee Shiinaha marka loo eego waddamada leh tusmooyinka horumarka bini'aadamka ee sarreeya waxay soo jeedinayaan in nidaam wax ku ool ah oo wax ku ool ah oo ka hortagga iyo ilaalinta kansarka loo baahan yahay si degdeg ah.Ogaanshaha hore ee kansarku waa mid ka mid ah walxaha ugu muhiimsan ee nidaamka daryeelka caafimaadka.Ogaanshaha hore ee kansarku wuxuu wanaajin karaa saadaasha iyo badbaadada marxaladda hore ee ku dhawaad dhammaan noocyada kansarka4.Xeeladaha baarista ee lagu guuleystay ayaa horseeday hoos u dhac weyn oo ku yimid heerka dhacdooyinka iyo dhimashada ee kansarka ilmo-galeenka, naaska, mindhicirka, iyo qanjirka 'prostate'.

Si loo gaaro ogaanshaha hore ee kansarka, si kastaba ha ahaatee, ma aha hawl fudud.Baarista bayoolajiga iyo saadaasha kansarka hore, ogaanshaha iyo xaqiijinta astaameeyayaasha hore ee ogaanshaha noole ee la isku halayn karo, iyo horumarinta tignoolajiyada goor hore ee la heli karo oo sax ah ayaa had iyo jeer ahaa caqabadaha ugu waaweyn ee geedi socodka4.Ogaanshaha saxda ah ee kansarku wuxuu kala saari karaa benign iyo nabarrada xun xun, taas oo ka caawinaysa in laga fogaado hababka aan loo baahnayn oo fududeeya maaraynta cudurrada dheeraadka ah.Xeeladaha ogaanshaha hore ee hadda jira waxaa ka mid ah biopsies ku salaysan endoscope, sawir-caafimaad, cytology, immunoassays, iyo tijaabooyinka biomarker5-7.Ahaanshaha faragelin iyo kharash badan, ka-qaadista endoscope-ku-salaysan waxay xambaarsan tahay culays dabiici ah oo culus sida habraac caafimaad oo weyn oo ku tiirsan shaqaale xirfad leh.Sida cytology, labada hababka baadhistu waxay ku xidhan yihiin xirfadlayaasha caafimaadka waxayna ku salaysan yihiin go'aan shakhsiyeed oo leh waxqabad ka fog qaab-dhismeedka8.Taas bedelkeeda, immunoassays-yada ayaa ah kuwo aan sax ahayn, marka loo eego heerarka sare ee been-abuurka ah.Sawir-qaadista caafimaadka, sida xeeladda baarista, waxay u baahan tahay qalab qaali ah iyo farsamoyaqaanno takhasus leh.Sidaa awgeed, sawirka caafimaadku aad buu u xaddidan yahay helitaanka oo hooseeya awgeed.Sababahaan oo dhan dartood, biomarkers waxay u muuqdaan inay yihiin ikhtiyaarka kaxaynta hore ee ogaanshaha kansarka.

Xidhiidhka: Yinshan Li iyo Wenqiang Yu

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

Aqoonsiga ORCID: https://orcid.org/0009-0005-3340-6802 iyo

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

La helay Ogosto 22, 2023;la aqbalay Oktoobar 12, 2023;

waxaa lagu daabacay onlayn November 28, 2023.

Waxaa laga heli karaa www.cancerbiomed.org

Sifo-Shatiga Caalamiga ah ee Aan Ganacsiga ahayn 4.0

Biomarkers waxa hadda loo kala saaraa borotiino, calaamade beddelka DNA, calaamadaha epigenetic, cilladaha koromosoomyada, calaamadaha RNA oo si toos ah uga soo jeeda burooyinka, ama jajabyo burooyinka si aan toos ahayn looga helay dheecaannada jidhka.Calaamadaha borotiinka ayaa ah kuwa ugu badan ee lagu dabaqo biomarkers ee baaritaanka kansarka iyo ogaanshaha.Barootiinka biomarkers, sida shaybaarayaasha baarista noolaha, waxaa xaddidaya u janjeera in ay saameeyaan nabarrada aan fiicneyn, taas oo keeneysa baaritaan dheeri ah iyo daaweyn dheeraad ah, sida lagu soo warramey α-fetoprotein iyo antigen-specific prostate (PSA) 9,10.Calaamadaha RNA waxaa ka mid ah qaababka muujinta hidde-sidaha iyo calaamadaha kale ee RNA ee aan codeeyn. Isku-darka muujinta hidde-sideyaasha RNA ayaa lagu ogaan karaa iyadoo la adeegsanayo muunado kaadida, dareenka taas oo ka fogayd mid lagu qanco (60%) ee burooyinka asaasiga ah, iyo ogaanshaha kuwaas oo kara waxaa saameeya dabeecadda nabaad guurka fudud ee RNA ee deegaanka caadiga ah11.Calaamadaha hidda-socodka iyo epigenetic labaduba waxay la kulmaan dhibaatada baahsanaanta burooyinka iyo xaddididda noocyada kansarka.

Methylation-ka DNA-da waxa uu ahaa musharrax xooggan oo ah ogaanshaha hore ee biomarker tan iyo markii ugu horreysay ee Feinberg lala xiriiriyay kansarka 198312. Methylation DNA ayaa lagu arkay dhammaan heerarka kansarka, horraantii marxaladda hore ee kansarka.Aberrant DNA hypermethylation waxay badanaa ka dhacdaa jasiiradaha CpG ee dhiirrigeliyeyaasha hidda-wadaha si looga hortago burooyinka.13,14.Daraasaduhu waxay sidoo kale soo jeediyeen in DNA-da hypermethylation aan caadi ahayn ay ku lug leedahay kor u qaadista nidaamiyeyaasha horumarinta15.Dooxada methylation DNA, oo sida caadiga ah lala xiriiriyo maamulayaasha korriinka iyo kansarka hypermethylated, ayaa laga yaabaa inay u beddelaan habka muujinta hidda-wadaha qaab-ku-tiirsanaan DNA-da oo xasilloon oo hoos u dhigaya xidhiidhka methylated histone H3K27me3 iyo borotiinnada polycomb ee la xidhiidha16,17.

Ka mid ah tirada badan ee calaamadaha methylation DNA ee la daabacay, dhowr ayaa si guul leh uga dooday suuqa;si kastaba ha ahaatee, calaamadaha methylation DNA ee hadda la baayac-mushtareeyay iyo qaybaha ogaanshaha ayaa weli si buuxda u furin suurtagalnimada in hore loo ogaado kansarka sababo badan dartood18.Iyadoo inta badan ay muujinayaan waxqabadka la aqbali karo iyadoo la adeegsanayo macluumaadka xogta, kuwan biomarkers waxay caadi ahaan u qabtaan si ka yar adduunka dhabta ah sababtoo ah shaybaarada dhabta ah ee adduunka ayaa badanaa aad u adag oo aan wakiil ka ahayn kuwa lagu doortay kaydka.Jiilka soo socda-ku-saleysan-ku-saleysan-ku-saleysan-ku-saleysan methylation-ka kansar-kala-duwan ee hore ayaa la muujiyey inuu leeyahay 16.8% kaliya iyo 40.4% dareenka marxaladda I iyo II kansarrada, siday u kala horreeyaan19.Tijaabooyinka ogaanshaha hore waxay u baahan yihiin xasillooni weyn iyo calaamado-soo-saarayaal sax ah.

Helitaanka kansarka caalamiga ah oo kaliya (UCOM) iyadoo la isticmaalayo meelaynta hagaha (GPS)

In kasta oo tobannaan sano oo cilmi-baaris kansar ah, ka-hortagga iyo daawaynta lagu qanco aan la xaqiijin.Habab cusub ayaa loo baahan yahay si ay cilmi-baarayaashu awood ugu yeeshaan inay si fiican u qiimeeyaan kansarka.23kii sano ee la soo dhaafay, 6 astaamood oo kansar ah, sida apoptosis ka baxsiga, duulaanka unugyada & metastasis, iwm., ayaa la balaariyay ilaa 14 iyada oo ay ku jiraan astaamo ay ka mid yihiin dib-u-habeeynta hidde-sidaha epi-genetic non-mutational iyo polymorphic microbiomes20,21.Marka tafaasiil dheeraad ah oo ku saabsan kansarka la soo bandhigo, aragtiyo badan ayaa lagu soo bandhigay cilmi-baarista kansarka.Cilmi-baarista kansarku waxay si tartiib tartiib ah u soo gashay jiho cusub oo laba jiho ah (mid guud iyo shakhsi ahaan).Iyada oo la horumarinayo kansarka saxda ah sannadihii u dambeeyay, diiradda cilmi-baarista kansarku waxay u janjeertaa daawaynta gaarka ah ee la beegsanayo iyo kala duwanaanta kansarka22.Markaa, biomarkers-ka kansarka ee dhawaan la aqoonsaday ayaa inta badan diiradda saaray noocyada kansarka gaarka ah, sida PAX6 kansarka qasabka ah23 iyo BMP3 ee kansarka mindhicirka24.Waxtarka biomarkers-ka gaarka ah ee noocyada kansarku way kala duwan yihiin, laakiin weli suurtogal uma aha in shakhsiyaadka u nugul inay isku mar isku mar sameeyaan baadhista dhammaan kansarka sababtoo ah xaddidnaanta helitaanka muunadda noolaha iyo qiimaha sarreeya.Way fiicnaan lahayd haddii aan aqoonsan karno hal, biomarker adag oo waxtar u leh dhammaan noocyada kansarka marxaladda dhow.

Si loo gaaro yoolka saxda ah, musharax biomarker ka wanaagsan waa in laga soo dhex xulaa liiska noocyada biomarker-ka ee suurtagalka ah.DNA methylation aberrations, oo ka mid ah dhammaan hidde-sideyaasha iyo astaamaha epigenetic, waxaa loo yaqaanaa inay la xiriiraan kansarka waana qaar ka mid ah kuwa ugu horreeya, haddii aysan ahayn marka hore, cilladaha kansarka la xiriira ee u dhaca si taariikhi ah.Baaritaanka methylation DNA wuxuu bilowday goor hore, laakiin waxaa caqabad ku noqday la'aanta hababka cilmi-baarista.Ka mid ah 28 milyan oo ka mid ah goobaha methylated CpG ee genome-ka, tiro la maarayn karo waa in la helaa oo la waafajiyaa genome-ka si loo fahmo tumorigenesis.Isku soo wada duuboo genome bisulfite (WGBS), kaas oo loo arko inuu yahay heerka dahabka ee taxanaha DNA methylation, wuxuu dabooli karaa kaliya 50% Cs ee unugyada kansarka sababtoo ah dabeecadda daaweynta bisulfite ee jebisa jajabyada DNA-da oo hoos u dhigta kakanaanta genome inta lagu jiro isbeddelka Cs-to-Ts25.Hababka kale, sida 450k chips, kaliya waxay daboolaan 1.6% ee genome methylation.Iyadoo lagu salaynayo xogta 450k, guddiga ogaanshaha methylation DNA wuxuu leeyahay 35.4% dareenka 6 nooc ee kansarka marxaladda I26.Xaddidaadda noocyada kansarka, waxqabadka liita, iyo buuqa ka dhasha hababka ogaanshaha ee habka falanqaynta ayaa noqday caqabadaha ugu waaweyn ee qaybaha ogaanshaha kansarka sanbabada.

Si loo baaro qaababka epigenetic ee unugyada inta lagu jiro burooyinka iyo metastasis-ka, waxaan sameynay GPS gaar ah oo loogu talagalay ogaanshaha DNA-da ee genome-ballaaran, kaas oo daboolaya ilaa 96% goobaha CpG ee 0.4 bilyan akhrinta25.GPS waa habka isku xigxiga ee bilateral iyadoo la adeegsanayo 3′ dhamaadka jajabka DNA-ga ee methyl-cytosines aan la bedeli karin ka dib daawaynta bisulfit ee haga isku toosinta xisaabinta methyl DNA ee 5′ dhamaadka iyadoo loo marayo isku xigxiga labada-dhamaadka ah (Jaantuska 1)25.Xarig hagaha methyl-cytosine, oo u dhaqmaysa sidii jaantus qaabaysan, waxa uu caawiyaa isku xidhka gobolka-GC-sare ee soo celiya xogta isku xigxiga ee aadka looga tagey ee WGBS dhaqameed.Muuqaalka sare ee daboolida GPS-ku wuxuu bixiyaa macluumaad aad u badan oo DNA-da methylation ah, kaas oo noo ogolaanaya inaan baarno astaamaha methylation-ka kansarka oo leh xallin aad u sareysa gobollada hore ee aan baaritaanku ku jirin.

GPS-ku waxa uu na siinayaa qalab awood leh oo lagu baadho isku midnimada kansarka, kaas oo si weyn u fududayn kara cilmi-baadhista kansarka oo suurtogal ah in la helo sharraxaad caalami ah oo ku saabsan tum-origenesis iyo metastasis.Iyadoo la falanqeynayo xogta GPS ee khadadka unugyada kansarka, dhacdo gaar ah ayaa marar badan la kulmay.Waxaa jiray tiro gobollo ah oo u muuqday inay si aan caadi ahayn u hypermethylated noocyo badan oo muunado kansar ah.Helitaankan lama filaanka ah ayaa markii dambe la ansixiyay si loogu adeego sidii UCOMs.In ka badan 7,000 oo muunado ah oo laga soo qaaday 17 nooc oo kansar ah oo ku jira kaydka Kansarka Genome Atlas (TCGA) ayaa la falanqeeyay, kuwaas oo aan aqoonsannay UCOM-gii ugu horreeyay, HIST1H4F, hiddo-wade laxiriira histone kaas oo ah hypermethylated dhammaan noocyada kansarka27.Taxane UCOM-yo ah ayaa markaa laga helay oo lagu ansixiyay xogta TCGA, xogta Gene Expression Omnibus (GEO), iyo muunado caafimaad oo caalami ah.Ilaa hadda, HIST1H4F, PCDHGB7, iyo SIX6 waa la helay oo loo ansixiyay sidii UCOMs.Helitaanka lama filaanka ah ee UCOMs waxay bixisaa jawaab xoog leh baahida loo qabo ogaanshaha hore ee kansarka.UCOM-yadu waxay bixiyaan xal lagu ogaanayo hal calaamad oo kansar oo badan.

Astaamaha UCOM-yada

Marka la ansixiyo, UCOM-yada waxaa la tusay inay soo bandhigaan afar astaamood oo waaweyn kuwaas oo awood u siinaya UCOM-yada inay dhaafaan waxtarka biomarkers hadda (Jaantuska 2).

U gaar ah xumaanta

UCOM-yadu waxay gaar u yihiin nabarrada kansarka ama kansarka ka horreeya mana saameeyaan isbeddellada jireed ee caadiga ah.Qaar ka mid ah calaamadaha kansarka la xiriira ee si weyn loogu dabaqay ogaanshaha hore iyo/ama baaritaanka ayaa horseeday ogaanshaha dheeraadka ah.Heerarka PSA ee sarreeya, qalab baaritaan caafimaad oo la aqoonsan yahay, ayaa sidoo kale lagu ogaadaa xaalado aan fiicneyn, sida hyperplasia qanjirka 'prostate' iyo prostatitis10.Baadhitaanka xad-dhaafka ah iyo daawaynta xad-dhaafka ah ee ka dhalatay waxay keentaa inay hoos u dhacdo tayada nolosha sababtoo ah saxarada, kaadida, iyo dhibaatooyinka galmada28.biomarkers kale oo borotiin ku saleysan oo si weyn loo isticmaalo goobta kiliinikada, sida CA-125, ma aysan dhalin faa'iidooyin la taaban karo iyada oo ay ku jiraan ogaanshaha xad dhaafka ah iyo daaweynta xad dhaafka ah29.Tilmaamaha sare ee UCOM-yada ee malignancies waxay ka fogaataa kuwan soo socda.UCOM, PCDHGB7, waxay si hufan u kala saartaa nabarrada squamous intraepithelial intraepithelial (HSILs) iyo kansarka makaanka afkiisa laga soo qaado muunadaha caadiga ah iyo nabarada hoose ee squamous intraepithelial lesions (LSILs), halka inta badan bio-calaamadaha kale ay ka sooci karaan kansarka ilmo-galeenka iyo kan caadiga ah30.Inkasta oo PCDHGB7 aysan ogaanin faraqa weyn oo u dhexeeya endometrium caadiga ah iyo hyperplasia endometrial, farqi weyn ayaa lagu ogaadaa inta u dhaxaysa endometrium caadiga ah iyo hyperplasia atypical, iyo xitaa kala duwanaansho weyn ayaa la ogaadaa inta u dhaxaysa endometrium caadiga ah iyo kansarka endometrial (EC) ee ku salaysan PCDHGB731.UCOM-yadu waxay gaar u yihiin nabarrada xun-xun ee xog-ururinta iyo muunadaha bukaan-socodka.Marka loo eego aragtida bukaanka, UCOM-yada gaarka ah waxay yareeyaan marinka fahamka calaamadaha kakan ee kala duwan ee hawl-qabad liita ee biomarkers iyo walaaca u dhigma inta lagu jiro habka qiimaynta.Marka loo eego aragtida dhakhtarka, UCOM-yada gaarka ah waxay ka soocaan malignancies iyo nabarrada aan fiicneyn, kuwaas oo ka caawiya kala soocidda bukaannada waxayna yareeyaan hababka caafimaad ee aan loo baahnayn iyo daaweynta dheeraadka ah.Sidaa darteed, UCOM-yada gaarka ah waxay yareeyaan dib-u-celinta nidaamka caafimaadka, waxay yareeyaan dhibaatada nidaamka, waxayna u diyaariyaan ilo caafimaad oo dheeraad ah kuwa u baahan.

Jaantuska 1 Habka socodka shaqada GPS ee ogaanshaha methylation DNA25.Khadka cawliga: galitaanka taxanaha DNA;khad cas: DNA oo lagu daweeyay T4 DNA polymerase, oo lagu beddelayo cytosine 5′-methylcytosine ee 3′ dhamaadka gelinta;buluug C oo aniga leh: cytosine methylated;buluug C: cytosine aan methylated;jaalaha T: thymine25.

Dhammaan ama waxba

UCOM-yadu waxay ku jiraan unugyada kansarka oo kaliya waxaana laga helaa ku dhawaad dhammaan unugyada kansarka.HIST1H4F waxaa loo ansaxiyay in lagu buufiyo ku dhawaad dhammaan noocyada burooyinka laakiin aan ahayn muunado caadi ah27.Sidoo kale, PCDHGB7 iyo SIX6 ayaa sidoo kale lagu muujiyay inay yihiin hypermethylated dhammaan shaybaarada burooyinka laakiin aan ahayn muunado caadi ah30-32.Sifadan gaarka ah waxay si weyn u wanaajisaa waxqabadka UCOM-yada marka loo eego xadka ogaanshaha iyo dareenka.In ka yar 2% unugyada kansarka ayaa lagu kala sooci karaa shaybaarada, taasoo ka dhigaysa UCOMs biomarker aad uga xasaasisan marka loo eego inta badan biomarkers30. Sida biomarker-ka loo isticmaalo ogaanshaha kansarka mindhicirka, isbeddellada KRAS waxay kaliya ku jiraan qiyaastii 36% kiisaska kansarka mindhicirka. soo jeedinaya karti-xumo ogaanshaha 33.Baahsanaanta hoose ee isbeddellada KRAS ee kansarka mindhicirka ayaa xaddidaya KRAS marka lagu daro biomarkers kale.Dhab ahaantii, isku-darka biomarkers ayaa laga yaabaa inay bilowga hore u muuqdaan kuwo rajo leh, laakiin had iyo jeer ma keenaan natiijo lagu qanco iyadoo muujinaya buuq aad u weyn oo ku saabsan falanqaynta ogaanshaha waxayna badanaa ku lug leedahay habab tijaabo ah oo aad u adag.Taas bedelkeeda, PCDHGB7 iyo UCOM-yada kale waxay ku jiraan dhammaan kansarrada.UCOM-yadu waxay ogaadaan qaybaha kansarka ee noocyada kala duwan ee shaybaarada kansarka iyagoo si sax ah u ciribtiraya hababka falanqaynta ee joojinta buuqa.Ma adka in kansar lagu ogaado muunad faro badan, laakiin aad bay u dhib badan tahay in kansarka lagu ogaado muunad yar.UCOM-yadu waxay awood u leeyihiin inay ogaadaan xaddi yar oo kansar ah.

Jaantuska 2 Astaamaha UCOM-yada.

Ogaanshaha kansarka ee ka horreeya isbeddellada cudurrada

UCOM-yada waxaa lagu ogaan karaa marxaladda kansarka ka hor ka hor isbeddelada cudurada.Sida biomarkers epigenetic, cilladaha UCOM waxay ku dhacaan marxalad hore marka loo eego cilladaha phenotypic waxaana lagu ogaan karaa inta lagu jiro tumorigenesis, horumarka, iyo metastasis34,35.Dareenka UCOM waqti ka dib waxay wanaajisaa waxqabadka UCOM ee ogaanshaha kansarka marxaladda hore iyo nabarada kansarka ka hor.Ogaanshaha kansarka hore ee ku salaysan biopsies iyo cytology waxay ku adkaan kartaa xitaa dhakhaatiirta khibradda leh.Hal-biopsy oo lagu helay colposcopy ayaa lagu soo warramey inay togan tahay 60.6% ee HSIL+ muunadaha.Biopsyo dheeri ah ayaa loo baahan yahay nabaro badan si loo kordhiyo dareenka36.Taas bedelkeeda, UCOM, PCDHGB7, waxay leedahay dareenka 82% ee shaybaarada HSIL+, taas oo dhaaftay dareenka biopsies iyo inta badan biomarkers30.Astaanta methylation-ka, FAM19A4, waxay leedahay dareenka 69% ee CIN2+, kaas oo la mid ah cytology, laakiin kama sooci karo CIN1 muunadaha caadiga ah37.UCOM-yada ayaa la tusay inay yihiin kuwo aad u xasaasisan oo hore u ogaanaya biomarker.Marka la barbar dhigo cilmi-baarayaasha ku salaysan khibradda, UCOM-yadu waxay leeyihiin dareen- ogaansho heersare ah oo loogu talagalay kansarka marxaladda hore, taas oo iyaduna gacan ka geysata horumarinta saadaalinta kansarka iyo badbaadada30.Intaa waxaa dheer, UCOM-yadu waxay bixiyaan madal lagu ogaan karo oo la heli karo meelaha ay ka maqan yihiin dhakhaatiirta cudurada wadnaha oo si weyn u wanaajinaya hufnaanta ogaanshaha.Nidaamyada sahaminta lebbiska iyo ogaanshaha, ogaanshaha UCOM waxay soo saartaa natiijooyin deggan oo sahlan oo loo tarjumo taas oo ku habboon nidaamka baarista ee u baahan shaqaale xirfad leh iyo ilo caafimaad oo yar.

Fudud in la ogaado

Hababka hadda ee ogaanshaha methyl DNA waa kuwo dhib badan oo waqti badan qaata.Inta badan hababka waxay u baahan yihiin isbeddelka bisulfit, kaas oo keena lumitaanka tayada muunada oo laga yaabo inay soo saarto natiijooyin aan degganayn oo aan sax ahayn.Soo saarista liidata ee ay keento daawaynta bisulfit waxay suurtogal u tahay inay u horseeddo jahawareer dhakhaatiirta iyo bukaanka oo ay sii farageliyaan daba-galka iyo/ama xeeladaha daawaynta.Sidaa darteed, waxaan sii wax ka bedelnay habka ogaanshaha UCOM si aan uga fogaano daaweynta dhibka leh ee bisulfit ee shaybaarada, u dejiso shuruudaha codsiga kiliinikada, iyo kor u qaadista helitaanka.Waxaan soo saarnay hab cusub anagoo adeegsanayna enzymes xaddidan xasaasiga ah oo ay weheliso waqtiga-dhabta ah ee fluorescent quantitative PCR (Me-qPCR) si loo qiyaaso heerka methylation ee UCOMs gudaha 3 h iyadoo la isticmaalayo habab fudud oo wax looga qabanayo (Jaantuska 3).Me-qPCR waxay qaadi kartaa noocyo kala duwan oo muunado ah, sida ururinta dareeraha jidhka iyo kaadida la iska soo ururiyay.Tijaabooyin caafimaad oo la ururiyey waa la farsamayn karaa, la kaydin karaa, oo si fudud ayaa loo sii wadi karaa ogaanshaha iyada oo la isticmaalayo soo saarista DNA-ga caadiga ah iyo si toos ah.DNA-da la soo saaray ayaa markaa si toos ah loogu dabaqi karaa goobta Me-qPCR ee falcelinta hal-dhari iyo natiijooyinka qiyaasida wax soo saarka.Ka dib falanqaynta natiijada fudud iyadoo la adeegsanayo moodooyinka ogaanshaha ee ku habboon oo la ansixiyay noocyada kansarka gaarka ah, go'aaminta kama dambaysta ah ee natiijooyinka ogaanshaha UCOM waxaa loo tarjumaa oo loo soo bandhigaa qiime nus-tiro ah.Qalabka Me-qPCR wuxuu ka sarreeyaa bisulfite-pyrosequencing dhaqameed ee ogaanshaha UCOM iyadoo la badbaadinayo 3 h ofbisulfite beddelka, marka loo eego nidaamka EZ DNA Methylation-Gold kit.Qalabka cusub ee ogaanshaha methylation wuxuu ka dhigayaa ogaanshaha UCOM mid xasiloon, ka saxsan, oo la heli karo30.

Jaantuska 3 Habka ogaanshaha UCOM-yada.Noocyada muunada waxa ka mid ah BALF si xirfadaysan loo muunadeeyay, buraashka Pap, iyo/ama kaadida la isa soo ururiyay.Habka soo saarista DNA-da waxaa lagu dejin karaa soosaar toos ah, kaas oo badeecadiisa ay si toos ah u ogaan karto qPCR.

Codsiga UCOM-yada

Kansarka sambabada

Kansarka sambabada waa kan labaad ee ugu badan ee la ogaado uguna halista badan aduunka oo dhan, isaga oo ka dhigan 11.4% kiisaska cusub iyo 18.0% dhimashada cusub1.Dhammaan baaritaannada, 85% waa kansarka sambabada unugyada aan yarayn (NSCLC) iyo 15% waa kansarka sambabada unugyada yaryar (SCLC), kaas oo leh heer sare oo malignancy38.Sawir-qaadis yar oo la xisaabiyay (LDCT) waa habka hadda lagu taliyay ee lagu baaro kansarka sanbabada waxaana la muujiyay inuu wanaajinayo ogaanshaha hore iyo dhimista dhimashada6;si kastaba ha ahaatee, gaar ahaan hoos u dhaca iyo helitaan la'aanta liidata awgeed, LDCT wali uma adeegin sidii hab baaris oo lagu qanco, si la mid ah calaamadaha kale ee kansarka caadiga ah, sida CEA39.Kharashyada iyo suurtagalnimada baadhitaannada la seegay iyo baadhista khaldan ee istaraatijiyadda baadhista LDCT waxay carqaladaynaysaa horumarka baadhista kansarka sanbabada40.HIST1H4F, UCOM, ayaa leh awood aad u weyn sida ogaanshaha hore ee biomarker ee dheecaanka bronchoalveolar (BALF)27.HIST1H4F waa hypermethylated ee adenocarcinoma sambabada iyo kansarka sanbabada unugyada squamous, oo leh gaar ahaan ogaanshaha 96.7% iyo dareenka 87.0% (Jaantuska 4A), iyo waxqabadka gaarka ah ee heerka I kansar27.HIST1H4F waxay leedahay gaar ah 96.5% iyo dareenka 85.4% ee NSCLC, iyo 96.5% iyo 95.7%, siday u kala horreeyaan, SCLC27.Intaa waxaa dheer, muunado siddeed nooc oo kale ah oo kansar ah, oo ay ku jiraan kansarka mindhicirka iyo mindhicirka, ayaa xaqiijiyay in HIST1H4F uu yahay hypermethylated dhammaan siddeed nooc27.

Kansarka ilmo-galeenka

Kansarka ilmo-galeenka ayaa ahaa kii afraad ee ugu badan ee lagu ogaado kansarka iyo sababta afraad ee ugu badan ee dhimashada kansarka ee haweenka sannadka 2020, taasoo ka dhigan 3.1% kiisaska cusub iyo 3.4% dhimashada kansarka la xiriirta ee caalamka1.Si meesha looga saaro kansarka ilma-mareenka marka la gaaro 2030, sida ay soo jeedisay WHO, waxaa lama huraan ah in goor hore la ogaado kansarka ilmo galeenka.Haddii lagu ogaado marxaladda hore, heerka badbaadada 5-sano wuxuu gaaraa 92% oo leh kansarka afka ilmagaleenka 41.Tilmaamaha Bulshada Kansarka Mareykanka (ACS) waxay soo jeedinayaan baaritaannada cytology-ga ilmo-galeenka, baaritaannada aasaasiga ah ee HPV, ama cotests ee baaritaanka42.Cytology-ga ilmo-galeenka ilmo-galeenka waa soo-gal oo kaliya wuxuu ogaan karaa 63.5% ee CIN2+ kiisaska37.

PCDHGB7, si ka duwan, waxay si fiican u qabatay isticmaalka Pap smears iyo dheecaanka siilka, waxayna si hufan u kala saari kartaa HSIL iyo LSIL marxalad aad u horeeysa.PCDHGB7 kaligeed waxay leedahay dareenka 100.0% iyo gaar ahaan 88.7% kansarka ilmo galeenka (Jaantuska 4B), iyo 82.1% dareenka iyo 88.7% gaar ahaan HSIL+ muunadaha30.PCDHGB7 waxa kale oo ay leedahay 90.9% xasaasi ah iyo 90.4% gaar ah ee muunadaha dheecaanka siilka ee kansarka ilma-mareenka, kuwaas oo aad u fudud in la qaado30.Marka lagu daro baaritaanka halista sare (hr) HPV ama Thinprep Cytology Test (TCT), PCDHGB7 waxay leedahay dareen kordhay 95.7% iyo gaar ahaan 96.2%, taasoo aad uga sareysa tii hrHPV test (20.3%), TCT (51.2%) ), iyo labada la isku daray (57.8%) kansarka ilmo galeenka30.PCDHGB7 ayaa sidoo kale lagu muujiyay in lagu buufiyo 17 nooc oo kansar ah oo ka yimid xogta TCGA, taasoo muujinaysa ku habboonaanta qoyska UCOM30.

Jaantuska 4 UCOMs ayaa lagu ansixiyay afar nooc oo kansar ah oo ku jira daraasado caafimaad oo ballaaran.A. Waxqabadka HIST1H4F, UCOM, ee ogaanshaha kansarka sanbabada ee 508 muunado.B. Waxqabadka PCDHGB7, UCOM, ee ogaanshaha kansarka ilmo galeenka ee 844 muunado.C. Waxqabadka PCDHGB7, UCOM, ee ogaanshaha kansarka endometrial ee 577 endometrial Pap iyo muunadaha burushka Tao.D. Waxqabadka SIX6, UCOM, ee ogaanshaha kansarka kaadi mareenka ee 177 muunado.

EC waa mid ka mid ah kansarka habka taranka haweenka ee ugu caansan adduunka oo dhan, iyada oo lagu qiyaasay 4.2 milyan xaaladood oo cusub iyo 1% dhimashada kansarka la xiriira sannadkii.Marka lagu guuleysto ogaanshaha marxaladda dhow, EC waa la daweyn karaa oo waxay leedahay heerka badbaadada 5-sano ee 95% marxaladda I kansarka.Bukaan-socodka leh calaamadaha, sida dhiig-baxa ilmo-galeenka ee aan caadiga ahayn, waxay helaan qiimeyn caafimaad oo xilliyeed ah waxayna maraan habraacyo ka-qaadis oo xanuun leh, inkastoo kaliya 5%-10% ugu dambeyntii ay soo baxaan EC43.Ultrasound-ka xubinta taranka ee xubinta taranka, sida habka ogaanshaha caadiga ah, waa mid aan la isku halleyn karin sababtoo ah awood la'aanta inay ka soocdo benign iyo isbeddellada endometrial ee xun iyo heerka sare ee been-abuurka ah44.

Isbarbardhigga isbarbardhigga serum CA-125, EC biomarker oo si ballaaran loo hirgeliyay, iyo PCDHGB7 ayaa la sameeyay.Serum CA-125 waxay lahayd dareenka 24.8%, taas oo soo jeedinaysa in CA-125 ay tahay calaamad aan ku filnayn EC inkastoo gaar ahaan 92.3%31.Ogaanshaha PCDHGB7 iyadoo la adeegsanayo muunado burushka Pap waxay keentay dareenka 80.65% iyo gaar ahaan 82.81% ee marxaladaha ECatall, halka burushka Tao uu lahaa dareenka 61.29% iyo gaar ahaan 95.31%31.Qaabka ogaanshaha PCDHGB7, ee ku salaysan Me-qPCR, wuxuu keenay dareenka 98.61%, gaar ahaan 60.5%, iyo saxnaanta guud ee 85.5%, iyadoo la adeegsanayo muunadaha burushka Pap iyo Tao (Jaantus 4C)31.

Kansarka kaadi mareenka

Kansarka kaadi mareenka, oo ka kooban kaadiheysta, miskaha kelyaha, iyo kansarka kaadi mareenka, ayaa ahaa kan toddobaad ee ugu badan ee laga helo adduunka 2020, kaasoo sababay 5.2% kiisaska cusub iyo 3.9% dhimashada1.Kansarka kaadi mareenka, oo ka badan 50% kuwaas oo ah kansarka kaadiheysta, ayaa ahaa kansarka afaraad ee ugu badan ee laga helo Mareykanka sanadka 2022, taasoo ka dhigan 11.6% kiisaska cusub ee la helay3.Qiyaastii 75% kansarka kaadiheysta waxaa loo kala saaraa sida kansarka kaadiheysta aan muruq ahayn ee ku xaddidan xuubka xuubka ama submucosa45.Baaritaanka cystoscopy-ga waa heerka dahabka ee lagu ogaanayo kansarka kaadi mareenka ee ay hirgeliso fluorescence in situ hybridization (FISH) iyo cytology tests.KALUUNKA iyo cytology waxay leeyihiin hawl-qabad ogaanshaha oo liidata, iyo cystoscopy-gu waa faragelin waxayna leedahay khatarta hoose ee unugyada yaryar ee maqan, dhaawacyada si khaldan u fasiraya, iyo suurtogalnimada inay keento faafidda ama soo noqoshada kansarka46.UCOM-kii hore ee la ansaxiyay, PCDHGB7, ayaa sidoo kale lagu muujiyay inuu yahay hypermethylated kansarka kaadi mareenka, oo leh aag ka hooseeya qalooca 0.86, taasoo soo jeedinaysa awoodda ogaanshaha ee suurtogalka ah30.Si loo sii ansixiyo UCOM-yo badan oo si wanaagsan loogu habeeyo noocyo badan oo muunado ah, SIX6, sheeko cusub oo UCOM ah, ayaa la baadhay oo muujiyay karti ogaanshaha ugu wanaagsan ee ogaanshaha hore ee kansarka kaadi mareenka iyadoo la adeegsanayo muunado kaadida ee goobta Me-qPCR.Ogaanshaha SIX6 iyadoo la adeegsanayo muunado kaadida ayaa muujisay dareen tartan ah oo ah 86.7% iyo gaar ahaan 90.8% (Jaantus 4D), iyada oo aan ahayn duullaan oo ay fududahay in la helo32.Awoodda SIX6 ee la socodka metastasis-ka iyo qiimeynta waxtarka daaweynta ayaa hadda ku socda baaritaan.

Mustaqbalka iyo caqabadaha

UCOM-yadu waxay leeyihiin waxqabad xooggan oo lagu ogaan karo kansarrada badan, laakiin waxaa jira shaqo badan oo u hadhay in la sameeyo.Waxaan ballaarinay liiska UCOM-yada waxaana si firfircoon u ansixnay UCOM-yada noocyo badan oo kansar ah, oo ay ku jiraan kuwa dhaqan ahaan ay adagtahay in la ogaado.Natiijooyinka ansixinta xogta xogta TCGA ayaa sii xoojiyay codsiga UCOM-yada noocyo badan oo kansar ah iyo xaalado badan.Baaritaan horudhac ah, UCOM-yada ayaa lagu muujiyay inay leeyihiin karti ogaanshaha cudurka cholangiocarcinomas iyo adenocarcinomas pancreatic, kuwaas oo ku dhow aan suurtagal ahayn in lagu ogaado marxaladda hore ee hababka baaritaanka hadda32,47.Awoodda lagu ogaanayo kansarrada dhifka ah ee leh UCOM-yada waxaa lagu isticmaali karaa DNA-da buro wareegaysa (ctDNA) iyada oo la wanaajiyey biopsy platform48.Daraasad ku lug leh baaritaanka DNA-ku-saleysan ee baaritaanka kansarka pan-kansarka ayaa keentay dareenka 57.9%49.Inkasta oo si gaar ah u sarreeya, waxqabadka guud wuxuu muujinayaa in weli ay jirto meel lagu hagaajin karo.

Sifooyinka gaarka ah ee UCOM-yada ayaa sidoo kale taageeray baaritaanka suurtagalnimada UCOM ee qiimeynta waxtarka daaweynta iyo kormeerka soo noqnoqda.Marka loo eego Shuruudaha Qiimaynta Jawaabta ee Burooyinka Adag (RECIST), sawirka caafimaadku waa habka lagu taliyay ee la socodka soo noqnoqda iyo qiimaynta waxtarka daaweynta, halka calaamadaha burooyinka keligood loo isticmaalo qiimaynta50.Xaqiiqda, si kastaba ha ahaatee, hababka sawir-qaadista ayaa si weyn u saameeya soo noqnoqda iyo waqtiga, sidaas darteedna waxay bukaannada u soo bandhigaan khatar sare iyo kharash51,52.SIX6 ayaa loo ansaxiyay inay u adeegaan sidii saadaal kansarka naasaha metastasis32.Korjoogteynta ctDNA-da-biopsy-ku-saleysan ee dareeraha ah ayaa awood u siinaya ilaalinta waqtiga-dhabta ah ee cudurrada haraaga ah ee ugu yar bilaha ka hor inta aan la ogaanin shucaaca, sida ugu habboon dib u dhigista iyo ka hortagga horumarka kansarka ee la xiriira soo noqoshada53.Natiijooyinka hordhaca ah waxay soo jeedinayaan in UCOMs ay ka tarjumayaan heerka hypermethylation kansarka wakhtiga dhabta ah isla markiiba ka dib qaliinka iyo daaweynta32.Dareenka sare ee ay muujiyeen UCOM-yada iyo ku-dhaqanka noocyo badan oo muunado ah oo aan faragelin lahayn ayaa u oggolaanaya UCOM-yada in ay u adeegaan sidii dib-u-soo-noqnoqosho sax ah oo dabagalka noolaha iyada oo la ilaalinayo u hoggaansanaanta bukaanka sare.

Isla markaana, gelitaanka dadweynaha ee imtixaanku waa arrin kale oo weyn oo u baahan dadaal dheeraad ah.In kasta oo iskaashiga ogaanshaha UCOM lagu qaatay cusbitaalo badan iyada oo la rajaynayo in laga faa'iidaysto bukaanno badan, ogaanshaha pro bono iyo baadhitaannada ayaa si firfircoon looga sameeyay miyiga Shiinaha.UCOMs waxay u baahan yihiin helitaan la wanaajiyey si ay ugu qalmaan sidii qalab baadhis oo macquul ah, gaar ahaan meelaha aan la horumarin.

Iyadoo natiijooyinka codsiga UCOM ee ogaanshaha hore ay yihiin kuwo rajo leh, waxyaabo badan oo aan la garanayn oo ku saabsan UCOM ayaa jira.Sahaminta firfircoon, cilmi baaris dheeraad ah ayaa dammaanad qaadaysa sababta UCOM-yadu ay guud ahaan uga jiraan kansarrada.Hababka sharciyeynta epigenetic-ka hoose ee ka hooseeya UCOMs ayaa mudan in baaritaan dheeraad ah lagu sameeyo, taas oo caddayn karta jihada cusub ee daaweynta kansarka.Ku soo noqoshada isdhexgalka u dhexeeya isku-naanshaha burada iyo kala duwanaanta, waxaan xiiseyneynaa sababta UCOM-yadu ay uga reebi karaan inta badan biomarkers kansarka kuwaas oo si adag ugu xiran noocyada kansarka gaarka ah.Doorka UCOM-aqoonsaday DNA methylation aberrations ee burooyinka, horumarka burada, iyo metastasis laguma go'aamin habka luminta iyo dib u soo celinta aqoonsiga unugga waxayna u baahan tahay kormeer dhamaystiran.Danta kale ee ugu weyni waxay ku jirtaa baaxadda isku darka astaamaha isku midka ah ee UCOMs oo leh calaamado unug-gaar ah oo rajada laga qabo in la soo dhawaado ogaanshaha saxda ah ee raadadka kansarka iyo aqoonsiga asalka unugyada burooyinka si ka duwan.UCOM-yadu waxay noqon karaan qalab ku habboon si looga hortago kansarka, lagu ogaado kansarka, oo ay suurtagal tahay in la difaaco oo laga takhaluso kansarka.

Taageero deeq

Shaqadan waxaa taageeray Barnaamijka Qaranka ee R&D ee Shiinaha (Deeq No. 2022BEG01003), Aasaaska Sayniska Dabiiciga ah ee Qaranka ee Shiinaha (Deeq Nos. 32270645 iyo 32000505), Deeq ka timid Guddiga Caafimaadka Gobolka Heilongjiang (Deeq No. 2020-111) , iyo Deeq ka timid Heze Science and Technology Institute (Deeq No. 2021KJPT07).

Hadalka khilaafka

Wei Li waa Agaasimaha R&D ee Shanghai Epiprobe Biotechnology Co., Ltd. Wenqiang Yu wuxuu u adeegaa Guddiga La-talinta Sayniska ee Epiprobe.W. Yu iyo Epiprobe waxay ogolaadeen shatiyada la sugayo ee shaqadan la xidhiidha.Dhammaan qorayaasha kale ma sheegaan dano iska soo horjeeda.

Wax ku biirinta qoraaga

Mashruucu wuu raray oo naqshadeeyay: Chengchen Qian iyo Wenqiang Yu.

Waxa uu qoray warqadda: Chengchen Qian.

Wuxuu sameeyay sawirada: Chengchen Qian.

Dib u eegay oo tafatiray qoraal-gacmeedka: Xiaolong Zou, Wei Li, Yinshan Li iyo Wenqiang Yu.

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doi: 10.20892/j.issn.2095-3941.2023.0313

Waqtiga boostada: Meey-07-2024