Pancreatic cancer nderimwe remamota akaipisisa pasi rose ane fungidziro yakaipa.Naizvozvo, modhi yekufanotaura yechokwadi inodiwa kuona varwere vari panjodzi huru yepancreatic cancer kugadzirisa kurapwa uye kugadzirisa kufungidzira kwevarwere ava.
Takawana Iyo Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq data kubva kuUCSC Xena dhatabhesi, yakaratidza immune-inoenderana nelncRNAs (irlncRNAs) kuburikidza nekuongorora kwekuwirirana, uye takaona mutsauko pakati peTCGA uye yakajairika pancreatic adenocarcinoma tishu.DEirlncRNA) kubva kuTCGA uye genotype tishu kutaura (GTEx) yepancreatic tishu.Imwezve univariate uye lasso regression ongororo yakaitwa kuti ivake prognostic siginecha mamodheru.Isu takazoverenga nzvimbo iri pasi pe curve uye takasarudza iyo yakakwana cutoff kukosha yekuzivisa varwere vane yakakwira- uye yakaderera-njodzi pancreatic adenocarcinoma.Kuenzanisa maitiro ekiriniki, immune cell infiltration, immunosuppressive microenvironment, uye chemotherapy resistance kune varwere vane high- uye yakaderera-njodzi pancreatic kenza.
Takaona 20 DEirlncRNA pairs uye takaisa varwere mumapoka maererano neyakakwana cutoff kukosha.Takaratidza kuti yedu yekufungidzira siginecha modhi ine basa rakakosha mukufanotaura kufungidzira kwevarwere vane PAAD.Iyo AUC yeROC curve ndeye 0.905 yekufanotaura kwegore rimwe, 0.942 yemakore maviri ekufanotaura, uye 0.966 yemakore matatu ekufanotaura.Varwere vane njodzi yakakura vaive nehuwandu hwekupona uye hwakaipa hunhu hwekiriniki.Isu takaratidza zvakare kuti varwere vari panjodzi huru havana immunosuppressed uye vanogona kukura kuramba immunotherapy.Kuongororwa kwemishonga inopesana nekenza yakadai sepaclitaxel, sorafenib, uye erlotinib inobva pamagetsi ekufungidzira maturusi angave akakodzera kune varwere vane ngozi yakawanda vane PAAD.
Pakazere, chidzidzo chedu chakagadzira nyowani yekufungidzira njodzi modhi yakavakirwa papaired irlncRNA, iyo yakaratidza kuvimbisa kukosha kwekufungidzira muvarwere vane pancreatic cancer.Yedu prognostic njodzi modhi inogona kubatsira kusiyanisa varwere vane PAAD vanokodzera kurapwa.
Pancreatic cancer ibundu rakashata rine mwero wakaderera wemakore mashanu ekupona uye giredhi repamusoro.Panguva yekuongororwa, varwere vazhinji vatova muzvikamu zvepamusoro.Mumamiriro ezvinhu eCCIDID-19 denda, vanachiremba uye vanamukoti vari pasi pekumanikidzwa kukuru pakurapa varwere vane cancer yepancreatic, uye mhuri dzevarwere dzinosanganawo nedzvinyiriro dzakawanda pakuita sarudzo dzekurapa [1, 2].Kunyangwe kufambira mberi kukuru kwakaitwa mukurapa kweDOADs, senge neoadjuvant therapy, kuvhiyiwa resection, radiation therapy, chemotherapy, targeted molecular therapy, uye immune checkpoint inhibitors (ICIs), vangangoita 9% yevarwere vanopona makore mashanu mushure mekuongororwa [3. ].], 4].Nemhaka yokuti zviratidzo zvekutanga zvepancreatic adenocarcinoma hazvifananidzi, varwere vanowanzoonekwa kuti vane metastases padanho repamusoro [5].Naizvozvo, kune murwere akapihwa, kurapwa kwakadzama kwakasarudzika kunofanirwa kuyera zvakanakira nekuipira kwese kusarudzwa kwekurapa, kwete kungorebesa kurarama, asiwo kuvandudza hupenyu hwehupenyu [6].Nokudaro, muenzaniso unoshanda wekufanotaura unodiwa kuti uongorore zvakakwana chirwere chemurwere [7].Nokudaro, kurapwa kwakakodzera kunogona kusarudzwa kuenzanisa kurarama uye hupenyu hwehupenyu hwevarwere vane PAAD.
Iyo yakaipa prognosis yePAAD inonyanya kukonzerwa nekuramba chemotherapy mishonga.Mumakore achangopfuura, immune checkpoint inhibitors yakashandiswa zvakanyanya mukurapa mamota akasimba [8].Nekudaro, kushandiswa kweICIs mupancreatic cancer hakuwanzo kubudirira [9].Saka, zvakakosha kuziva varwere vanogona kubatsirwa neICI therapy.
Yakareba isina kukodha RNA (lncRNA) imhando yeRNA isina kukodha ine zvinyorwa>200 nucleotides.LncRNAs dzakapararira uye dzinoita 80% yezvinyorwa zvevanhu [10].Basa guru rebasa rakaratidza kuti lncRNA-based prognostic models inogona kunyatsofanotaura kufungidzira kwevarwere [11, 12].Semuenzaniso, 18 autophagy-yakabatana lncRNAs yakaonekwa kuti ibudise masiginecha ekufungidzira mukenza yemazamu [13].Mamwe matanhatu e-lncRNA ane hukama nekudzivirira akashandiswa kumisikidza maitiro ekufungidzira eglioma [14].
Mupancreatic cancer, zvimwe zvidzidzo zvakagadzira lncRNA-yakavakirwa masiginecha kufanotaura kufungidzira kwemurwere.A 3-lncRNA siginicha yakasimbiswa mupancreatic adenocarcinoma ine nzvimbo iri pasi peROC curve (AUC) ye 0.742 chete uye kurarama kwese (OS) ye3 makore [15].Pamusoro pezvo, lncRNA kutaura kukosha kunosiyana pakati pemajenomes akasiyana, akasiyana data mafomati, uye varwere vakasiyana, uye kuita kweiyo fungidziro modhi haina kugadzikana.Naizvozvo, isu tinoshandisa novel modelling algorithm, pairing uye iteration, kugadzira kusadzivirirwa-kwakanangana nelncRNA (irlncRNA) siginecha kugadzira yakanyatso uye yakagadzikana yekufungidzira modhi [8].
Normalized RNAseq data (FPKM) uye kliniki pancreatic cancer TCGA uye genotype tissue expression (GTEx) data yakawanikwa kubva kuUCSC XENA database (https://xenabrowser.net/datapages/).Mafaira eGTF akawanikwa kubva mudura reEnsemble ( http://asia.ensembl.org ) uye akashandiswa kuburitsa lncRNA kutaura maprofiles kubva kuRNAseq.Takadhawunirodha majini ane hukama nekudzivirira kubva kuImmPort dhatabhesi (http://www.immport.org) uye takaona ine hukama nelncRNAs (irlncRNAs) tichishandisa correlation analysis (p <0.001, r> 0.4).Kuzivikanwa kweirlncRNAs (DEirlncRNAs) nekuyambuka irlncRNAs uye kuratidzwa zvakasiyana lncRNAs dzakatorwa kubva kuGEPIA2 database (http://gepia2.cancer-pku.cn/#index) muTCGA-PAAD cohort (|logFC| > 1 uye FDR <0.05).
Iyi nzira yakambotaurwa [8].Kunyanya, tinovaka X kutsiva paired lncRNA A uye lncRNA B. Kana iyo yekutaura kukosha kwelncRNA A yakakwirira kudarika kukosha kwekutaura kwelncRNA B, X inotsanangurwa se1, kana X inotsanangurwa se 0. Nokudaro, tinogona kuwana matrix ye0 kana - 1. Axis yakatwasuka yematrix inomiririra sampuli yega yega, uye yakatwasuka axis inomiririra imwe neimwe DEirlncRNA peya ine kukosha kwe0 kana 1.
Univariate regression analysis inoteverwa neLasso regression yakashandiswa kuratidza prognostic DEirlncRNA pairs.Iyo lasso regression analysis yakashandiswa 10-fold cross-validation yakadzokororwa 1000 times (p <0.05), ine 1000 random stimuli per run.Kana kuwanda kweyega yega DEirlncRNA pair yakapfuura ka100 muma 1000 cycles, DEirlncRNA pairs dzakasarudzwa kuti dzivake prognostic risk model.Isu takazoshandisa iyo AUC curve kuti tiwane iyo yakakwana cutoff kukosha yekuisa varwere vePAAD mumapoka ane njodzi huru uye yakaderera.Kukosha kweAUC yemhando yega yega yakaverengerwa uye yakarongwa senge curve.Kana iyo curve ichisvika padanho repamusoro rinoratidza kukosha kweAUC yakakura, maitiro ekuverenga anomira uye modhi inoonekwa seyakanakisa mumiriri.1-, 3- uye 5-gore ROC curve mhando dzakavakwa.Univariate uye multivariate regression analyzes yakashandiswa kuongorora yakazvimirira inofanotaura kuita kweiyo prognostic risk model.
Shandisa maturusi manomwe ekudzidza immune cell infiltration rates, kusanganisira XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, uye CIBERSORT.Data yekupinza masero edziviriro yakatorwa kubva mudura reTIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Musiyano wezviri mukati memasero ekudzivirira-anopinda mukati memapoka epamusoro-uye akaderera-ane njodzi yemuenzaniso wakagadzirwa wakaongororwa uchishandisa Wilcoxon yakasainwa-rank test, mhedzisiro inoratidzwa mu square graph.Spearman correlation ongororo yakaitwa kuongorora hukama pakati pengozi mamaki kukosha uye maseru-anopinda mukati.Iyo inokonzeresa coefficient inoratidzwa selollipop.Iko kukosha kwepakati kwakaiswa pa p <0.05.Maitiro acho akaitwa uchishandisa iyo R package ggplot2.Kuti tiongorore hukama huri pakati pemuenzaniso uye mazinga ekutaura kwemajini ane chekuita neiyo immune cell infiltration rate, takaita ggstatsplot package uye violin plot visualization.
Kuongorora maitiro ekurapa kwekiriniki epancreatic cancer, isu takaverenga iyo IC50 yeanowanzo shandiswa chemotherapy mishonga muTCGA-PAAD cohort.Kusiyana kwehafu inhibitory concentrations (IC50) pakati pezvikwata zvepamusoro uye zvishoma-zvishoma zvakaenzaniswa nekushandisa Wilcoxon sign-rank test, uye migumisiro inoratidzwa sebhokisi rebhokisi rinogadzirwa uchishandisa pRrophetic uye ggplot2 muR. Nzira dzose dzinoenderana nemitemo yakakodzera uye mitemo.
Kufambiswa kwebasa rekudzidza kwedu kunoratidzwa muMufananidzo 1. Kushandisa kuongorora kuwirirana pakati pelncRNAs uye majini ane hutachiona, takasarudza 724 irlncRNAs ne p <0.01 uye r> 0.4.Isu takazoongorora iyo yakasarudzika lncRNAs yeGEPIA2 (Mufananidzo 2A).Huwandu hwe223 irlncRNAs dzakaratidzwa zvakasiyana pakati pepancreatic adenocarcinoma uye yakajairika pancreatic tishu (|logFC| > 1, FDR <0.05), inonzi DEirlncRNAs.
Kuvakwa kwekufanofungidzira njodzi mhando.(A) Volcano chirongwa chezvinoratidzwa zvakasiyana lncRNAs.(B) Kugoverwa kwelasso coefficients ye20 DEirlncRNA pairs.(C) Musiyano wakasarudzika weiyo LASSO coefficient kugovera.(D) Sango rakarongeka rinoratidza univariate regression analysis ye20 DEirlncRNA pairs.
Isu takazogadzira 0 kana 1 matrix nekubatanidza 223 DEirlncRNAs.Huwandu hwe13,687 DEirlncRNA pairi dzakaonekwa.Mushure mekunge univariate uye lasso regression analysis, 20 DEirlncRNA pairs dzakazoedzwa kuti dzivake prognostic risk model (Mufananidzo 2B-D).Zvichienderana nemhedzisiro yeLasso uye yakawanda regression analysis, takaverenga chiyero chenjodzi kumurwere wega wega muTCGA-PAAD cohort (Table 1).Zvichienderana nemhedzisiro yelasso regression analysis, takaverenga chiyero chenjodzi kumurwere wega wega muTCGA-PAAD cohort.Iyo AUC yeROC curve yaive 0.905 yekufanotaura kwe1-gore njodzi modhi, 0.942 ye2-gore kufanotaura, uye 0.966 ye3-gore kufanotaura (Mufananidzo 3A-B).Isu takaisa yakaringana cutoff kukosha kwe3.105, stratified TCGA-PAAD cohort varwere mumapoka epamusoro-nepasi-panjodzi, uye akaronga mhedzisiro yekupona uye kugoverwa kwengozi yemurwere wega wega (Mufananidzo 3C-E).Kuongororwa kweKaplan-Meier kwakaratidza kuti kupona kwevarwere vePAAD muboka repamusoro-soro kwaive kwakaderera kudarika kwevarwere vari muboka rakaderera (p <0.001) (Mufananidzo 3F).
Kutendeseka kweprognostic njodzi mhando.(A) ROC yeiyo prognostic njodzi modhi.(B) 1-, 2-, uye 3-gore ROC prognostic njodzi mhando.(C) ROC yeprognostic risk model.Inoratidza nzvimbo yakakwana yekucheka.(DE) Kugovera kwehupenyu hwekupona (D) uye njodzi zvibodzwa (E).(F) Kaplan-Meier kuongororwa kwevarwere vePAAD mumapoka makuru uye akaderera.
Isu takaongorora zvakare kusiyana kwezvibodzwa zvengozi nemakiriniki maitiro.Iyo strip plot (Mufananidzo 4A) inoratidza hukama hwese pakati pehutano hwekiriniki uye huwandu hwengozi.Kunyanya, varwere vakwegura vaiva nehuwandu hwehuwandu hwehuwandu (Mufananidzo 4B).Mukuwedzera, varwere vane danho rechipiri vaiva nepamusoro-soro yengozi kupfuura varwere vane danho I (Mufananidzo 4C).Nezve tumor giredhi muvarwere vePAAD, giredhi 3 varwere vaive nepamusoro njodzi mamakisi kupfuura giredhi 1 uye 2 varwere (Mufananidzo 4D).Isu takaenderera mberi nekuita univariate uye multivariate regression ongororo uye takaratidza kuti njodzi chikamu (p <0.001) uye zera (p = 0.045) yaive yakazvimirira prognostic zvinhu muvarwere vane PAAD (Mufananidzo 5A-B).ROC curve yakaratidza kuti chikamu chengozi chaive chakakwirira kune mamwe maitiro ekiriniki mukufanotaura 1-, 2-, uye 3-gore kupona kwevarwere vane PAAD (Mufananidzo 5C-E).
Clinical maitiro e prognostic njodzi mhando.Histogram (A) inoratidza (B) zera, (C) bundu nhanho, (D) bundu giredhi, njodzi mamaki, uye murume kana mukadzi wevarwere vari muTCGA-PAAD cohort.**p <0.01
Kuzvimiririra kufungidzira kuongororwa kweprognostic risk models.(AB) Univariate (A) uye multivariate (B) regression inoongorora ye prognostic njodzi mhando uye kiriniki maitiro.(CE) 1-, 2-, uye 3-gore ROC ye prognostic njodzi mhando uye kiriniki maitiro
Naizvozvo, takaongorora hukama pakati penguva uye zvibodzwa zvengozi.Takaona kuti chikamu chengozi muvarwere vePAAD chakanga chakanyatsopindirana neCD8 + T masero uye NK masero (Mufananidzo 6A), zvichiratidza kudzvinyirirwa kushanda kwezvirwere muboka rine ngozi.Isu takaongororawo mutsauko wekupinda mumasero ekudzivirira mukati memapoka epamusoro uye akaderera uye akawana mhedzisiro yakafanana (Mufananidzo 7).Pakanga pasina kupinda mukati kweCD8 + T masero uye NK masero muboka renjodzi huru.Mumakore achangopfuura, immune checkpoint inhibitors (ICIs) yakashandiswa zvakanyanya mukurapa mamota akasimba.Nekudaro, kushandiswa kweICIs mupancreatic cancer hakuna kumbobudirira.Naizvozvo, isu takaongorora ratidziro yea immune checkpoint majini mumapoka akanyanya- uye akaderera ane njodzi.Takaona kuti CTLA-4 uye CD161 (KLRB1) yakanyanyisa muboka rakaderera (Mufananidzo 6B-G), zvichiratidza kuti varwere vePAAD vari muboka rakaderera vangave vane hanya neCI.
Correlation analysis of prognostic risk model uye immune cell infiltration.(A) Kuwirirana pakati peprognostic njodzi modhi uye immune cell infiltration.(BG) Inoratidza gene kutaura mumapoka makuru uye akaderera.(HK) IC50 kukosha kune chaiwo anticancer mishonga mumapoka akakwirira uye akaderera.*p <0.05, **p <0.01, ns = haina kukosha
Isu takaongororazve kushamwaridzana pakati pengozi zvibodzwa uye zvakajairika chemotherapy agents muTCGA-PAAD cohort.Isu takatsvaga anowanzo shandiswa anticancer zvinodhaka mupancreatic cancer uye takaongorora misiyano mune yavo IC50 kukosha pakati pepamusoro-uye yakaderera-nengozi mapoka.Zvigumisiro zvakaratidza kuti IC50 inokosha yeAZD.2281 (olaparib) yakanga yakakwirira muboka repamusoro-soro, zvichiratidza kuti varwere vePAAD vari muboka repamusoro-soro vanogona kupikisa AZD.2281 kurapwa (Mufananidzo 6H).Pamusoro pezvo, iyo IC50 tsika dzepaclitaxel, sorafenib, uye erlotinib dzaive dzakaderera muboka rine njodzi huru (Mufananidzo 6I-K).Isu takaona zvakare 34 anticancer mishonga ine yakakwira IC50 kukosha muboka rine njodzi uye makumi matatu nemana anticancer mishonga ine yakaderera IC50 kukosha muboka rine njodzi (Table 2).
Hazvigone kurambwa kuti lncRNAs, mRNAs, uye miRNAs aripo zvakanyanya uye anoita basa rakakosha mukukura kwegomarara.Pane humbowo hwakakwana hunotsigira basa rakakosha remRNA kana miRNA mukufanotaura kupona kwese mumhando dzinoverengeka dzegomarara.Pasina kupokana, akawanda ekufungidzira engozi mamodheru zvakare akavakirwa palncRNAs.Somuenzaniso, Luo et al.Zvidzidzo zvakaratidza kuti LINC01094 inoita basa rakakosha mukuwanda kwePC uye metastasis, uye kutaura kwepamusoro kweLINC01094 kunoratidza kusapona kwevarwere vepancreatic cancer [16].Chidzidzo chakapihwa naLin et al.Zvidzidzo zvakaratidza kuti kuderedzwa kwelncRNA FLVCR1-AS1 kwakabatana nekusaziva kufungidzira mupancreatic cancer varwere [17].Nekudaro, maLncRNA ane hukama nekudzivirira haana kukurukurwa zvakanyanya maererano nekufanotaura kupona kwese kwevarwere vegomarara.Munguva pfupi yapfuura, basa rakawanda rave rakatarisana nekuvaka maitiro enjodzi yekufanotaura kupona kwevarwere vekenza uye nekudaro kugadzirisa nzira dzekurapa [18, 19, 20].Kune kukura kucherechedzwa kwebasa rakakosha rekudzivirira kwekudzivirira mukutanga kenza, kufambira mberi, uye kupindura kune marapirwo akadai sechemotherapy.Ongororo dzakawanda dzakasimbisa kuti bundu-inopinda masero ekudzivirira ekudzivirira anoita basa rakakosha mukupindura cytotoxic chemotherapy [21, 22, 23].Iyo tumor immune microenvironment chinhu chakakosha mukupona kwechirwere chevarwere [24, 25].Immunotherapy, kunyanya ICI therapy, inoshandiswa zvakanyanya mukurapa mamota akasimba [26].Majini ane chekuita nekudzivirira kwemuviri anoshandiswa zvakanyanya kugadzira mhando dzengozi dzekufungidzira.Somuenzaniso, Su et al.Iyo immune-inoenderana neprognostic yengozi modhi yakavakirwa paprotein-coding majini kufanotaura kufungidzira kwevarwere vegomarara reovarian [27].Asina-coding majini akadai selncRNAs akakodzerawo kuvaka prognostic njodzi mhando [28, 29, 30].Luo et al akaedza maLncRNA mana ane hukama nekudzivirira uye akavaka muenzaniso wekufungidzira wengozi yegomarara remuchibereko [31].Khan et al.Zvose zve 32 zvakasiyana-siyana zvinyorwa zvakaratidzwa zvakaonekwa, uye zvichibva pane izvi, muenzaniso wekufanotaura ne 5 zvinyorwa zvakakosha zvakasimbiswa, izvo zvakarongwa sechinhu chakakurudzirwa zvikuru chekufanotaura kuti biopsy-yakaratidza kurambwa kwakanyanya mushure mekuiswa kwetsvo [32].
Mazhinji emamodheru aya anobva pamatanho ekutaura kwemajini, angave maprotein-coding genes kana asina-coding genes.Nekudaro, iro geni rinogona kuve neakasiyana ekutaura maitiro mune akasiyana genomes, data mafomati uye muvarwere vakasiyana, zvichitungamira kune isina kugadzikana fungidziro mumamodhi ekufungidzira.Muchidzidzo ichi, takavaka modhi inonzwisisika ine mapeya maviri elncRNAs, akazvimirira pane chaiyo yekutaura kukosha.
Muchidzidzo ichi, takaona irlncRNA kekutanga kuburikidza nekuongorora kwekubatanidza nemajini ane hukama nekudzivirira.Takaongorora 223 DEirlncRNAs nekusanganisa nelncRNA dzakaratidzwa zvakasiyana.Chechipiri, isu takavaka 0-kana-1 matrix zvichibva pane yakabudiswa DEirlncRNA pairing nzira [31].Isu takazoita univariate uye lasso regression ongororo yekuona prognostic DEirlncRNA pairs uye kuvaka yekufungidzira njodzi yemhando.Isu takaongororazve kushamwaridzana pakati pengozi zvikoro uye kliniki maitiro muvarwere vane PAAD.Takaona kuti yedu yekufungidzira njodzi yemuenzaniso, seyakazvimirira prognostic factor muvarwere vePAAD, inogona kunyatsosiyanisa varwere vepamusoro kubva kune vakaderera-giredhi uye varwere vepamusoro kubva kuvarwere vakaderera.Uye zvakare, iyo AUC kukosha kweROC curve yeprognostic njodzi modhi yaive 0.905 ye1-gore fungidziro, 0.942 ye2-gore fungidziro, uye 0.966 yemakore matatu ekufanotaura.
Vatsvakurudzi vakashuma kuti varwere vane CD8 + T cell infiltration vainyanya kufunga nezveICI kurapwa [33].Kuwedzera kwemukati we cytotoxic masero, CD56 NK masero, NK masero uye CD8 + T masero mu tumor immune microenvironment inogona kuva chimwe chezvikonzero zvebundu suppressive effect [34].Zvidzidzo zvekare zvakaratidza kuti mazinga akakwirira e-bundu-infiltrating CD4 (+) T uye CD8 (+) T akabatanidzwa zvakanyanya nekugara kwenguva refu [35].Yakashata CD8 T cell infiltration, yakaderera neoantigen mutoro, uye yakanyanya immunosuppressive tumor microenvironment inotungamirira kushayikwa kwekupindura kuICI therapy [36].Takaona kuti chikamu chengozi chakanga chakashata chakabatanidzwa neCD8 + T masero uye NK masero, zvichiratidza kuti varwere vane zvikwereti zvakanyanya vangave vasina kukodzera kurapwa kweICI uye vane chirwere chakaipisisa.
CD161 chiratidzo chemuurayi chaiwo (NK) masero.CD8 + CD161+ CAR-yakashandurwa T masero anopindirana akasimbiswa mu vivo antitumor efficacy muHER2 + pancreatic ductal adenocarcinoma xenograft models [37].Immune checkpoint inhibitors inotarisa cytotoxic T lymphocyte yakabatana neprotein 4 (CTLA-4) uye yakarongwa sero rekufa protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) nzira uye ine mukana mukuru munzvimbo dzakawanda.Tsanangudzo yeCTLA-4 uye CD161 (KLRB1) yakaderera mumapoka makuru ane ngozi, zvichiratidza kuti varwere vane zvikwereti zvakanyanya vangave vasina kukodzera kurapwa kweICI.[38]
Kuti tiwane nzira dzokurapa dzakakodzera kuvarwere vane ngozi yakawanda, takaongorora mishonga yakasiyana-siyana yemishonga uye takaona kuti paclitaxel, sorafenib, uye erlotinib, iyo inoshandiswa zvakanyanya kune varwere vane PAAD, inogona kunge yakakodzera kune varwere vane ngozi yakawanda vane PAAD.[33].Zhang et al akawana kuti kuchinja mune chero DNA kukuvadza mhinduro (DDR) nzira inogona kutungamirira kuhurombo husina kunaka muvarwere vekenza yeprostate [39].The Pancreatic Cancer Olaparib Ongoing (POLO) muedzo wakaratidza kuti kurapwa kwekuchengetedza neolaparib kwakagara kwenguva refu-kusina kupona kana kuchienzaniswa ne placebo mushure mekutanga-mutsara weplatinum-based chemotherapy mune varwere vane pancreatic ductal adenocarcinoma uye germline BRCA1 / 2 mutations [40].Izvi zvinopa tarisiro yakakosha yekuti mhedzisiro yekurapa ichavandudza zvakanyanya muboka iri revarwere.Muchidzidzo ichi, IC50 inokosha yeAZD.2281 (olaparib) yakanga yakakwirira muboka repamusoro-soro, zvichiratidza kuti varwere vePAAD vari muboka repamusoro-soro vangave vasingagadziriswi kurapwa neAZD.2281.
Mienzaniso yekufungidzira muchidzidzo ichi inoburitsa mhedzisiro yakanaka, asi yakavakirwa pakufanotaura kwekuongorora.Nzira yekusimbisa sei izvi mhedzisiro nekliniki data mubvunzo unokosha.Endoscopic yakanaka tsono aspiration ultrasonography (EUS-FNA) yave nzira yakakosha yekuongorora maronda akasimba uye ekunze kwepancreatic nekunzwa kwe85% uye chaiyo ye98% [41].Kuuya kweEUS fine-needle biopsy (EUS-FNB) tsono dzinonyanya kubva pane zvinofungidzirwa zvakanakira pamusoro peFNA, senge yakakwira yekuongororwa kwechokwadi, kuwana masampuli anochengetedza histological chimiro, uye nekudaro kugadzira immune tishu yakakosha kune kumwe kuongororwa.tsvina yakakosha [42].Ongororo yakarongeka yezvinyorwa yakasimbisa kuti FNB tsono (kunyanya 22G) inoratidza kugona kwakanyanya mukukohwa matishu kubva kupancreatic masses [43].Mumakiriniki, nhamba shomanana chete yevarwere inokodzera kuvhiyiwa kukuru, uye varwere vazhinji vane zviputi zvisingashande panguva yekutanga kuongororwa.Mukuita kwekiriniki, chikamu chiduku chevarwere chinokodzera kuvhiyiwa kukuru nokuti varwere vakawanda vane zviputi zvisingashande panguva yekutanga kuongororwa.Mushure mekusimbiswa kwepathological neEUS-FNB nedzimwe nzira, kurapwa kwakamisikidzwa kusiri kwekuvhiya senge chemotherapy kunowanzo kusarudzwa.Chirongwa chedu chetsvagurudzo chinotevera ndechekuedza muenzaniso wekufungidzira wechidzidzo ichi mukuvhiya uye kusavhiya cohorts kuburikidza nekuongorora kudzoreredza.
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Nguva yekutumira: Sep-22-2023