Gomarara repancreatic nderimwe remagomarara akaipisisa pasi rose ane fungidziro yakaipa. Saka, panodiwa nzira chaiyo yekufanotaura kuti vanhu vari panjodzi huru yekubatwa negomarara repancreas vagadziriswe uye vagadzirise fungidziro yevarwere ava.
Takawana data reThe Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq kubva kuUCSC Xena database, takaona immune-related lncRNAs (irlncRNAs) kuburikidza ne correlation analysis, uye takaona mutsauko uripo pakati peTCGA ne normal pancreatic adenocarcinoma tissues. DEirlncRNA) kubva kuTCGA uye genotype tissue expression (GTEx) ye pancreatic tissue. Kumwe kuongorora kwe univariate uye lasso regression kwakaitwa kuti pave nema prognostic signature models. Takazoverenga nzvimbo iri pasi pe curve ndokuona kuti ndiyo yakanakisisa cutoff value yekuziva varwere vane high-and-low-risk pancreatic adenocarcinoma. Kuti tienzanise hunhu hwekiriniki, immune cell infiltration, immunosuppressive microenvironment, uye chemotherapy resistance muvarwere vane high-and-low-risk pancreatic cancer.
Takawana 20 DEirlncRNA pairs ndokuisa varwere mumapoka zvichienderana nehuwandu hwakakodzera hwe cutoff value. Takaratidza kuti modhi yedu yeprognostic signature ine basa guru mukufanotaura fungidziro yevarwere vane PAAD. AUC yeROC curve i0.905 yefungidziro yegore rimwe, 0.942 yefungidziro yegore maviri, uye 0.966 yefungidziro yemakore matatu. Varwere vane njodzi huru vaive nehuwandu hwakaderera hwekupona uye hunhu hwakaipa hwekiriniki. Takaratidzawo kuti varwere vane njodzi huru vane dziviriro yemuviri uye vanogona kuramba immunotherapy. Kuongororwa kwemishonga yekurwisa kenza yakadai sepaclitaxel, sorafenib, uye erlotinib zvichibva pazvishandiso zvekufungidzira zvemakomputa kunogona kukodzera varwere vane njodzi huru vane PAAD.
Zvose zvakazara, chidzidzo chedu chakagadzira modhi itsva yengozi yekufanotaura yakavakirwa pairing irlncRNA, iyo yakaratidza kukosha kwekufanotaura kune varwere vane kenza yepancreas. Modhi yedu yengozi yekufanotaura inogona kubatsira kusiyanisa varwere vane PAAD vakakodzera kurapwa.
Gomarara repancreatic igomarara rine huwandu hushoma hwekupona kwemakore mashanu uye giredhi repamusoro. Panguva yekuongororwa, varwere vazhinji vanenge vatove muzvikamu zvepamusoro. Mumamiriro edenda reCOVID-19, vanachiremba nevanamukoti vanenge vari pasi pekumanikidzwa kukuru pakurapa varwere vane gomarara repancreatic, uye mhuri dzevarwere dzinosanganawo nekumanikidzwa kwakawanda pakuita sarudzo dzekurapa [1, 2]. Kunyangwe kufambira mberi kukuru kwakaitwa mukurapa kweDOADs, senge neoadjuvant therapy, surgical resection, radiation therapy, chemotherapy, targeted molecular therapy, uye immune checkpoint inhibitors (ICIs), varwere vanongosvika 9% chete vanopona makore mashanu mushure mekuongororwa [3]. ], 4]. Nekuti zviratidzo zvekutanga zvepancreatic adenocarcinoma hazviwanzoitiki, varwere vanowanzoonekwa vaine metastases padanho repamusoro [5]. Naizvozvo, kumurwere akapihwa, kurapwa kwakazara kunofanirwa kuyera zvakanakira nekuipira kwesarudzo dzese dzekurapa, kwete kungowedzera nguva yekurarama, asiwo kuvandudza hupenyu [6]. Nokudaro, modhi inoshanda yekufanotaura inodiwa kuti iongorore nemazvo fungidziro yemurwere [7]. Saka, kurapwa kwakakodzera kunogona kusarudzwa kuti kuenzane nekurarama kwevarwere vane PAAD.
Kusafanotaura zvakanaka kwePAAD kunonyanya kukonzerwa nekusagona kurapwa nemishonga yechemotherapy. Mumakore achangopfuura, mishonga inodzivirira immune checkpoint yave ichishandiswa zvakanyanya mukurapa bundu rakasimba [8]. Zvisinei, kushandiswa kweICIs mukenza yepancreatic hakuwanzobudirira [9]. Saka, zvakakosha kuziva varwere vanogona kubatsirwa neICI therapy.
RNA refu isina makodhi (lncRNA) imhando yeRNA isina makodhi ine zvinyorwa zvinopfuura mazana maviri zve nucleotides. MaLncRNA akapararira uye anoumba 80% ye transcriptome yemunhu [10]. Basa guru rakaratidza kuti mamodheru ekufanotaura akavakirwa pa lncRNA anogona kufanotaura zvinobudirira mafambiro emurwere [11, 12]. Semuenzaniso, ma lncRNA gumi nemasere ane chekuita ne autophagy akaonekwa kuti anogadzira zviratidzo zvekufanotaura mukenza yemazamu [13]. Mamwe ma lncRNA matanhatu ane chekuita ne immune system akashandiswa kusimbisa zviratidzo zvekufanotaura zve glioma [14].
Mukenza yepancreatic, zvimwe zvidzidzo zvakaratidza masiginecha akavakirwa pa lncRNA kuti zvifanotaura mhedzisiro yemurwere. Siginecha ye 3-lncRNA yakawanikwa mu pancreatic adenocarcinoma ine nzvimbo iri pasi peROC curve (AUC) ye 0.742 chete uye kupona kwese (OS) kwemakore matatu [15]. Pamusoro pezvo, kukosha kwekutaura kwe lncRNA kunosiyana pakati pema genomes akasiyana, mafomati akasiyana edata, uye varwere vakasiyana, uye mashandiro emuenzaniso wekufanotaura haana kugadzikana. Saka, tinoshandisa algorithm itsva yekuenzanisira, kusanganisa uye kudzokorora, kugadzira masiginecha ane chekuita ne immunity lncRNA (irlncRNA) kuti tigadzire modhi yekufanotaura yakanyatsojeka uye yakagadzikana [8].
Data reRNAseq rakajairika (FPKM) uye clinical pancreatic cancer TCGA uye genotype tissue expression (GTEx) zvakatorwa kubva kuUCSC XENA database (https://xenabrowser.net/datapages/). Mafaira eGTF akawanikwa kubva kuEnsembl database (http://asia.ensembl.org) uye akashandiswa kubvisa ma profiles e lncRNA expression kubva kuRNAseq. Takadhawunirodha majini ane chekuita ne immunity kubva kuImmPort database (http://www.immport.org) uye takaona ma immunity-related lncRNAs (irlncRNAs) tichishandisa correlation analysis (p < 0.001, r > 0.4). Kuzivikanwa kwe differentially expressioned irlncRNAs (DEirlncRNAs) nekuyambuka irlncRNAs uye differentially expression lncRNAs dzakatorwa kubva kuGEPIA2 database (http://gepia2.cancer-pku.cn/#index) muTCGA-PAAD cohort (|logFC| > 1 uye FDR) <0.05).
Nzira iyi yakambotaurwa kare [8]. Zvikuru, tinogadzira X kuti titsive lncRNA A ne lncRNA B. Kana kukosha kwekutaura kwe lncRNA A kwakakwira kupfuura kukosha kwekutaura kwe lncRNA B, X inotsanangurwa se 1, zvikasadaro X inotsanangurwa se 0. Saka, tinogona kuwana matrix ye 0 kana - 1. Mutsetse wepamusoro we matrix unomiririra sample yega yega, uye mutsetse wepamusoro unomiririra peya yega yega ye DEirlncRNA ine kukosha kwe 0 kana 1.
Kuongororwa kweUnivariate regression kwakateverwa neLasso regression kwakashandiswa kuongorora mapeya eDEirlncRNA ekufanotaura. Kuongororwa kwelasso regression kwakashandisa 10-fold cross-validation yakadzokororwa ka1000 (p < 0.05), ne1000 random stimuli parun. Kana frequency yepeya yega yega yeDEirlncRNA yaipfuura ka100 muma cycles 1000, mapeya eDEirlncRNA akasarudzwa kugadzira modhi yengozi yekufanotaura. Takabva tashandisa AUC curve kuti tiwane cutoff value yakakwana yekuronga varwere vePAAD mumapoka ane njodzi huru nedzishoma. AUC value yemodhi yega yega yakaverengerwawo uye yakarongwa se curve. Kana curve ikasvika panzvimbo yepamusoro inoratidza AUC value yepamusoro, maitiro ekuverenga anomira uye modhi inoonekwa seyakanakisa. Mamodhi eROC curve e1-, 3- uye 5-year akagadzirwa. Kuongororwa kweUnivariate uye multivariate regression kwakashandiswa kuongorora kushanda kwekufungidzira kwakazvimirira kwemodhi yengozi yekufanotaura.
Shandisa maturusi manomwe kuti udzidze mwero wekupinda kwemasero emuviri, anosanganisira XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, uye CIBERSORT. Data rekupinda kwemasero emuviri rakatorwa kubva kuTIMER2 database (http://timer.comp-genomics.org/#tab-5817-3). Musiyano uripo pakati pemasero anopinda mumuviri pakati pemapoka ane njodzi huru neasina njodzi emuenzaniso wakagadzirwa wakaongororwa uchishandisa Wilcoxon signed-rank test, mhedzisiro yacho inoratidzwa mu square graph. Spearman correlation analysis yakaitwa kuti iongorore hukama huripo pakati pe risk score values nemasero anopinda mumuviri. Coefficient yekubatana yakabuda inoratidzwa se lollipop. Muganho wekukosha wakaiswa pa p < 0.05. Maitiro acho akaitwa uchishandisa R package ggplot2. Kuti tiongorore hukama huripo pakati pemuenzaniso nemazinga ekutaura kwemajini ane chekuita ne immune cell infiltration rate, takaita ggstatsplot package uye violin plot visualization.
Kuti tiongorore maitiro ekurapa kenza yepancreas, takaverenga IC50 yemishonga yechemotherapy inowanzoshandiswa muTCGA-PAAD cohort. Musiyano uripo pakati pemapoka ane njodzi huru neasina njodzi wakaenzaniswa uchishandisa bvunzo yeWilcoxon signed-rank, uye mhedzisiro yacho inoratidzwa semabhokisi akagadzirwa uchishandisa pRRophetic neggplot2 muR. Nzira dzese dzinoenderana nemirairo nemaitiro akakodzera.
Mafambiro ebasa redu anoratidzwa muMufananidzo 1. Tichishandisa ongororo yekubatana pakati pe lncRNAs nemajini ane chekuita nekudzivirira muviri, takasarudza ma irlncRNAs 724 ane p < 0.01 uye r > 0.4. Takazoongorora ma lncRNAs anoratidzwa zvakasiyana eGEPIA2 (Mufananidzo 2A). Huwandu hwema irlncRNAs 223 hwakaratidzwa zvakasiyana pakati pe pancreatic adenocarcinoma ne normal pancreatic tissue (|logFC| > 1, FDR < 0.05), anonzi DEirlncRNAs.
Kugadzirwa kwemamodheru engozi dzinofanotaurwa. (A) Plot yevolcano ye lncRNAs dzakaratidzwa zvakasiyana. (B) Kugoverwa kwema lasso coefficients e20 DEirlncRNA pairs. (C) Kusiyana kwechikamu chemukana wekugoverwa kweLASSO coefficient. (D) Plot yesango inoratidza ongororo ye univariate regression ye20 DEirlncRNA pairs.
Takazogadzira matrix ine 0 kana 1 nekubatanidza maDEirlncRNA mazana maviri nemakumi maviri nematatu. Mapeya eDEirlncRNA anosvika 13,687 akawanikwa. Mushure mekuongorora kweunivariate nelasso regression, mapeya eDEirlncRNA makumi maviri akazoedzwa kuti pave nemuenzaniso wengozi yekufanotaura (Mufananidzo 2B-D). Zvichibva pamhedzisiro yeLasso nekuongorora kwemultiple regression, takaverenga chibodzwa chengozi kumurwere wega wega muTCGA-PAAD cohort (Tafura 1). Zvichibva pamhedzisiro yekuongorora kwelasso regression, takaverenga chibodzwa chengozi kumurwere wega wega muTCGA-PAAD cohort. AUC yeROC curve yaive 0.905 yekufanotaura kwemuenzaniso wengozi wegore rimwe, 0.942 yekufanotaura kwemakore maviri, uye 0.966 yekufanotaura kwemakore matatu (Mufananidzo 3A-B). Takaisa chiyero chakanaka che3.105, takaisa varwere veTCGA-PAAD mumapoka ane njodzi huru nedzishoma, uye takaronga mhedzisiro yekupona uye kugoverwa kwezviratidzo zvenjodzi kumurwere wega wega (Mufananidzo 3C-E). Ongororo yaKaplan-Meier yakaratidza kuti kupona kwevarwere vePAAD muboka rine njodzi huru kwakaderera zvakanyanya pane kwevarwere vari muboka rine njodzi shoma (p < 0.001) (Mufananidzo 3F).
Kushanda kwemamodheru enjodzi dzekufanotaura. (A) ROC yemuenzaniso wenjodzi dzekufanotaura. (B) Mamodheru enjodzi dzekufanotaura eROC yemakore 1, 2, uye 3. (C) ROC yemuenzaniso wenjodzi dzekufanotaura. Inoratidza nzvimbo yakanakisisa yekugumisa. (DE) Kugoverwa kwemamiriro ekurarama (D) uye mamakisi enjodzi (E). (F) Kuongorora kwaKaplan-Meier kwevarwere vePAAD mumapoka ane njodzi huru nedzisina njodzi.
Takaongororazve mutsauko wezviratidzo zvengozi zvichienderana nezviratidzo zvekiriniki. Chidimbu (Mufananidzo 4A) chinoratidza hukama hwese huripo pakati pezviratidzo zvekiriniki nezviratidzo zvengozi. Kunyanya, varwere vakuru vaive nezviratidzo zvengozi zvakanyanya (Mufananidzo 4B). Pamusoro pezvo, varwere vane danho rechipiri vaive nezviratidzo zvengozi zvakanyanya kupfuura varwere vane danho rekutanga (Mufananidzo 4C). Nezvegiredhi regomarara muvarwere vePAAD, varwere vegiredhi rechitatu vaive nezviratidzo zvengozi zvakanyanya kupfuura varwere vegiredhi 1 nerechipiri (Mufananidzo 4D). Takawedzera kuita ongororo ye univariate uye multivariate regression uye takaratidza kuti zviratidzo zvengozi (p < 0.001) nezera (p = 0.045) zvaive zvinhu zvakazvimiririra zvekufanotaura muvarwere vane PAAD (Mufananidzo 5A-B). Rondedzero yeROC yakaratidza kuti zviratidzo zvengozi zvaive zvakakwirira pane zvimwe zviratidzo zvekiriniki mukufanotaura kurarama kwemakore 1, 2, uye 3 kwevarwere vane PAAD (Mufananidzo 5C-E).
Hunhu hwekiriniki hwemhando dzenjodzi dzekufanotaura. Histogram (A) inoratidza (B) zera, (C) danho rebundu, (D) giredhi rebundu, mamakisi enjodzi, uye murume kana mukadzi wevarwere vari muboka reTCGA-PAAD. **p < 0.01
Ongororo yakazvimirira yekufungidzira yemamodheru enjodzi dzekufanotaura. (AB) Ongororo yeUnivariate (A) uye multivariate (B) yekudzokorora mamodheru enjodzi dzekufanotaura uye hunhu hwekiriniki. (CE) ROC yemakore 1-, 2-, uye 3 yemamodheru enjodzi dzekufanotaura uye hunhu hwekiriniki.
Saka, takaongorora hukama huripo pakati penguva nezviratidzo zvenjodzi. Takaona kuti zviratidzo zvenjodzi muvarwere vePAAD zvaive zvakabatana zvakasiyana nemasero eCD8+ T nemasero eNK (Mufananidzo 6A), zvichiratidza kudzvinyirirwa kwebasa rekudzivirira muviri muboka rine njodzi huru. Takaongororawo musiyano wekupindwa kwemasero ekudzivirira muviri pakati pemapoka ane njodzi huru neasina njodzi uye takawana mhedzisiro yakafanana (Mufananidzo 7). Kwakanga kusina kupinda kwemasero eCD8+ T nemasero eNK muboka rine njodzi huru. Mumakore achangopfuura, mishonga inodzivirira immune checkpoint (ICIs) yakashandiswa zvakanyanya mukurapa bundu rakasimba. Zvisinei, kushandiswa kweICIs mukenza yepancreatic hakuna kumbobudirira. Saka, takaongorora kuratidzwa kwemajini ekudzivirira immune checkpoint mumapoka ane njodzi huru neasina njodzi huru. Takaona kuti CTLA-4 neCD161 (KLRB1) zvakashandiswa zvakanyanya muboka rine njodzi shoma (Mufananidzo 6B-G), zvichiratidza kuti varwere vePAAD muboka rine njodzi shoma vanogona kunge vachinzwa ICI.
Kuongororwa kwekubatana kwemuenzaniso wengozi yekufanotaura uye kupinda kwemasero emuviri. (A) Kubatana pakati pemuenzaniso wengozi yekufanotaura uye kupinda kwemasero emuviri. (BG) Inoratidza kuratidzwa kwemajini mumapoka ane njodzi huru nedzishoma. (HK) IC50 values yemishonga chaiyo yekurwisa kenza mumapoka ane njodzi huru nedzishoma. *p < 0.05, **p < 0.01, ns = hazvina kukosha
Takaongororazve hukama huripo pakati pezviratidzo zvengozi nemishonga yechemotherapy inowanikwa muboka reTCGA-PAAD. Takatsvaga mishonga inowanzoshandiswa yekurwisa kenza mukenza yepancreatic uye takaongorora mutsauko uripo muhuwandu hwavo hweIC50 pakati pemapoka ane njodzi huru neasina njodzi. Zvakabuda zvakaratidza kuti kukosha kweIC50 kweAZD.2281 (olaparib) kwakakwira muboka rine njodzi huru, zvichiratidza kuti varwere vePAAD vari muboka rine njodzi huru vanogona kunge vasingadi kurapwa neAZD.2281 (Mufananidzo 6H). Pamusoro pezvo, huwandu hweIC50 hwepaclitaxel, sorafenib, uye erlotinib hwakaderera muboka rine njodzi huru (Mufananidzo 6I-K). Takaonazve mishonga 34 yekurwisa kenza ine huwandu hweIC50 hwakakwira muboka rine njodzi huru uye 34 yekurwisa kenza ine huwandu hweIC50 hwakaderera muboka rine njodzi huru (Tafura 2).
Hazvigone kurambwa kuti lncRNAs, mRNAs, uye miRNAs zviripo zvakanyanya uye zvinoita basa rakakosha mukukura kwegomarara. Pane humbowo hwakawanda hunotsigira basa rakakosha remRNA kana miRNA mukufanotaura kupona kwese mumhando dzakasiyana dzegomarara. Pasina mubvunzo, mamodheru mazhinji engozi dzekufanotaura akavakirwawo pa lncRNAs. Semuenzaniso, Luo et al. Zvidzidzo zvakaratidza kuti LINC01094 inoita basa guru mukuwedzera kwePC uye metastasis, uye kuratidzwa kwakanyanya kweLINC01094 kunoratidza kusapona zvakanaka kwevarwere vegomarara regomarara [16]. Chidzidzo chakapihwa naLin et al. Zvidzidzo zvakaratidza kuti kudzikiswa kwe lncRNA FLVCR1-AS1 kwakabatana nekufanotaura zvakaipa kwevarwere vegomarara regomarara [17]. Zvisinei, ma lncRNA ane chekuita nekudzivirira muviri haanyanyi kukurukurwa maererano nekufanotaura kupona kwese kwevarwere vegomarara. Munguva pfupi yapfuura, basa rakawanda rave richitariswa pakuvaka mamodheru engozi dzekufanotaura kupona kwevarwere vegomarara uye nokudaro kugadzirisa nzira dzekurapa [18, 19, 20]. Kune kukura kwekuziva kwebasa guru rekudzivirira muviri rinopinda mukutanga kwekenza, kufambira mberi, uye kupindura kumishonga yakaita sechemotherapy. Ongororo dzakawanda dzakasimbisa kuti masero ekudzivirira muviri anopinda mukenza ane basa rakakosha mukupindura kuchemotherapy ine chepfu [21, 22, 23]. Nzvimbo yekudzivirira muviri ine tumor chinhu chakakosha mukupona kwevarwere vane tumor [24, 25]. Immunotherapy, kunyanya ICI therapy, inoshandiswa zvakanyanya mukurapa tumor yakasimba [26]. Majini ane chekuita neimmune anoshandiswa zvakanyanya kugadzira mamodheru engozi dzekufanotaura. Semuenzaniso, Su et al. Muenzaniso wengozi dzekufanotaura dzine chekuita neimmune wakavakirwa pamajini e-protein-coding kufanotaura mafambiro evarwere vekenza ye ovarian [27]. Majini asina-coding akadai se lncRNAs akakodzerawo kugadzira mamodheru engozi dzekufanotaura [28, 29, 30]. Luo et al vakaedza ma lncRNA mana ane chekuita neimmune uye vakavaka modheru yekufanotaura njodzi yekenza yemuromo wechibereko [31]. Khan et al. Makopi makumi matatu nemaviri akanyorwa zvakasiyana-siyana akawanikwa, uye zvichibva pane izvi, muenzaniso wekufanotaura une magwaro mashanu akakosha wakagadzwa, uyo wakakurudzirwa sechishandiso chinokurudzirwa zvikuru chekufanotaura kurambwa kwechirwere mushure mekuisirwa itsvo [32].
Mazhinji emamodeli aya akavakirwa pamazinga ekutaura kwemajini, angave majini ekunyora mapuroteni kana majini asiri ekunyora makodhi. Zvisinei, jini rimwe chete rinogona kuva nemaonero akasiyana mumajini akasiyana, mafomati edata uye muvarwere vakasiyana, zvichikonzera kufungidzira kusina kugadzikana mumamodeli ekufanotaura. Muchidzidzo ichi, takagadzira modhi inonzwisisika ine mapeya maviri e-lncRNA, isina chekuita nemaonero chaiwo.
Muchidzidzo ichi, takaona irlncRNA kekutanga kuburikidza nekuongorora kubatana kwemajini ane chekuita neimmune. Takaongorora maDEirlncRNA mazana maviri nemakumi maviri nematatu kuburikidza nekusanganisa ma lncRNA akasiyana-siyana. Chechipiri, takagadzira matrix ye0-kana-1 zvichibva panzira yekubatanidza yeDEirlncRNA yakaburitswa [31]. Takazoita analyses ye univariate ne lasso regression kuti tione ma prognostic DEirlncRNA pairs uye kuvaka predictive risk model. Takaongororazve hukama huripo pakati pe risk scores nehunhu hwekiriniki muvarwere vane PAAD. Takaona kuti prognostic risk model yedu, se prognostic factor yakazvimirira muvarwere vePAAD, inogona kusiyanisa varwere vepamusoro kubva kuvarwere vegiredhi rakaderera uye varwere vepamusoro kubva kuvarwere vegiredhi rakaderera. Pamusoro pezvo, AUC values yeROC curve yeprognostic risk model yaive 0.905 ye 1-year forecast, 0.942 ye 2-year forecast, uye 0.966 ye 3-year forecast.
Vaongorori vakataura kuti varwere vane huwandu hwakanyanya hweCD8+ T cell vainyanya kunzwa kurapwa neICI [33]. Kuwedzera kwehuwandu hwemasero ane chepfu, masero eCD56 NK, masero eNK uye masero eCD8+ T mu tumor immune microenvironment kungave chimwe chezvikonzero zvekudzvinyirira bundu [34]. Zvidzidzo zvekare zvakaratidza kuti huwandu hwakanyanya hweCD4(+) T uye CD8(+) T zvinopinda bundu zvakabatana zvakanyanya nekurarama kwenguva refu [35]. Kusapinda zvakanaka kwemasero eCD8 T, mutoro wakaderera we neoantigen, uye immune system microenvironment zvinodzvinyirira immune tumor zvinotungamira mukushaya mhinduro kuICI therapy [36]. Takaona kuti njodzi yaive yakabatana zvisina kunaka nemasero eCD8+ T nemasero eNK, zvichiratidza kuti varwere vane huwandu hwakanyanya hwenjodzi vangave vasina kukodzera kurapwa neICI uye vane fungidziro yakaipa.
CD161 chiratidzo chemasero anouraya (NK). Masero eT anotorwa neCD8+CD161+ CAR anobatsira mukudzivirira bundu mumuviri muHER2+ pancreatic ductal adenocarcinoma xenograft models [37]. Mishonga inorwisa immune checkpoint inotarisa cytotoxic T lymphocyte associated protein 4 (CTLA-4) uye programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathways uye ine mukana mukuru munzvimbo dzakawanda. Kuonekwa kweCTLA-4 neCD161 (KLRB1) kwakaderera mumapoka ane njodzi huru, zvichiratidzawo kuti varwere vane zviratidzo zvine njodzi huru vanogona kusakodzera kurapwa neICI. [38]
Kuti tiwane nzira dzekurapa dzakakodzera varwere vane njodzi huru, takaongorora mishonga yakasiyana-siyana yekurwisa kenza uye takaona kuti paclitaxel, sorafenib, uye erlotinib, iyo inoshandiswa zvakanyanya muvarwere vane PAAD, inogona kukodzera varwere vane njodzi huru vane PAAD. [33]. Zhang nevamwe vakaona kuti kuchinja mune chero nzira yeDNA damage response (DDR) kunogona kutungamira kumhedzisiro yakaipa muvarwere vane kenza yeprostate [39]. Kuedzwa kwePancreatic Cancer Olaparib Ongoing (POLO) kwakaratidza kuti kurapwa kwekuchengetedza neolaparib kunotora nguva refu pasina kufambira mberi kana tichienzanisa neplacebo mushure me first-line platinum-based chemotherapy muvarwere vane pancreatic ductal adenocarcinoma uye germline BRCA1/2 mutations [40]. Izvi zvinopa tariro huru yekuti mhedzisiro yekurapa ichavandudzika zvakanyanya muboka iri revarwere. Muchidzidzo ichi, kukosha kweIC50 kweAZD.2281 (olaparib) kwaive kwakakwira muboka rine njodzi huru, zvichiratidza kuti varwere vePAAD vari muboka rine njodzi huru vanogona kunge vasingadi kurapwa neAZD.2281.
Mamodheru ekufanotaura ari muchidzidzo ichi anounza mhedzisiro yakanaka yekufanotaura, asi akavakirwa pakufanotaura kwekuongorora. Maitiro ekusimbisa mhedzisiro iyi nedata rekiriniki mubvunzo unokosha. Endoscopic fine needle aspiration ultrasonography (EUS-FNA) yave nzira inokosha yekuongorora zvipembenene zvepancreatic zvakasimba uye zviri kunze kwepancreatic zvine sensitivity ye85% uye specificity ye98% [41]. Kuuya kwetsono dzeEUS fine-needle biopsy (EUS-FNB) kwakavakirwa zvakanyanya pamabhenefiti akaonekwa pamusoro peFNA, akadai sekururama kwakanyanya kwekuongorora, kuwana sampuro dzinochengetedza chimiro chehistological, uye nokudaro kugadzira immune tishu dzakakosha kune kumwe kuongororwa. special staining [42]. Ongororo yakarongeka yezvinyorwa yakasimbisa kuti tsono dzeFNB (kunyanya 22G) dzinoratidza kushanda kwepamusoro mukuunganidza tissue kubva kupancreatic masses [43]. Mukiriniki, nhamba shoma chete yevarwere inokodzera kuvhiyiwa kwakanyanya, uye varwere vazhinji vane tumors dzisingarapike panguva yekutanga kuongororwa. Mukiriniki, chikamu chidiki chete chevarwere chinokodzera kuvhiyiwa kwakanyanya nekuti varwere vazhinji vane tumors dzisingarapike panguva yekutanga kuongororwa. Mushure mekusimbiswa kwechirwere neEUS-FNB nedzimwe nzira, kurapwa kwakajairika kusina kuvhiyiwa kwakadai sechemotherapy kunowanzo sarudzwa. Chirongwa chedu chekutsvagisa chinotevera ndechekuedza modhi yekufanotaura kwechidzidzo ichi mumakorokoza ekuvhiya neasina kuvhiyiwa kuburikidza nekuongorora kwakadzokororwa.
Zvose zvakazara, chidzidzo chedu chakagadzira modhi itsva yengozi yekufanotaura yakavakirwa pairing irlncRNA, iyo yakaratidza kukosha kwekufanotaura kune varwere vane kenza yepancreas. Modhi yedu yengozi yekufanotaura inogona kubatsira kusiyanisa varwere vane PAAD vakakodzera kurapwa.
Dataseti dzakashandiswa uye dzakaongororwa muchidzidzo chazvino dzinowanikwa kubva kumunyori anoenderana nadzo kana zvikakumbirwa zvine musoro.
Sui Wen, Gong X, Zhuang Y. Basa rekubatsira munhu kuti azvibatsire mukugadzirisa manzwiro asina kunaka panguva yedenda reCOVID-19: chidzidzo chakasiyana-siyana. Int J Ment Health Nurs [chinyorwa chemagazini]. 2021 06/01/2021;30(3):759–71.
Sui Wen, Gong X, Qiao X, Zhang L, Cheng J, Dong J, nevamwe. Maonero emhuri pamusoro pekusarudza dzimwe nzira mumakamuri ekuchengetwa kwevarwere: ongororo yakarongeka. INT J NURS STUD [chinyorwa chemagazini; ongororo]. 2023 01/01/2023;137:104391.
Vincent A, Herman J, Schulich R, Hruban RH, Goggins M. Kenza yepancreatic. Lancet. [Nyaya yeJournal; rutsigiro rwekutsvagisa, NIH, extramural; rutsigiro rwekutsvagisa, hurumende iri kunze kweUS; ongororo]. 2011 08/13/2011;378(9791):607–20.
Ilic M, Ilic I. Kupararira kwegomarara repancreas. World Journal of Gastroenterology. [Chinyorwa cheJournal, ongororo]. 2016 11/28/2016;22(44):9694–705.
Liu X, Chen B, Chen J, Sun S. Nomogram itsva ine chekuita netp53 yekufanotaura kupona kwese kwevarwere vane kenza yepancreatic. BMC Cancer [journal article]. 2021 31-03-2021;21(1):335.
Xian X, Zhu X, Chen Y, Huang B, Xiang W. Mhedzisiro yekurapa kwakatarisana nemhinduro pakuneta kunokonzerwa nekenza muvarwere vekenza yemudumbu vanowana chemotherapy: bvunzo yakadzorwa isina kurongeka. Mukoti wekenza. [Chinyorwa cheJournal; bvunzo yakadzorwa isina kurongeka; chidzidzo ichi chinotsigirwa nehurumende iri kunze kweUnited States]. 2022 05/01/2022;45(3):E663–73.
Zhang Cheng, Zheng Wen, Lu Y, Shan L, Xu Dong, Pan Y, nevamwe. Mazinga emushonga wecarcinoembryonic antigen (CEA) mushure mekuvhiyiwa anofanotaura mhedzisiro mushure mekuvhiyiwa kwekenza yemudumbu muvarwere vane mazinga akajairwa eCEA vasati vavhiyiwa. Center for Translational Cancer Research. [Journal article]. 2020 01.01.2020;9(1):111–8.
Hong Wen, Liang Li, Gu Yu, Qi Zi, Qiu Hua, Yang X, nevamwe. MaLNCRNA ane chekuita neimmune system anogadzira zviratidzo zvitsva uye anofanotaura mamiriro ekudzivirira emuviri ekenza yehepatocellular yemunhu. Mol Ther Nucleic acids [Journal article]. 2020 2020-12-04;22:937 - 47.
Toffey RJ, Zhu Y., Schulich RD Kurapa kenza yepancreatic: zvipingamupinyi uye kubudirira. Ann Gastrointestinal Surgeon [Journal Article; review]. 2018 07/01/2018;2(4):274–81.
Hull R, Mbita Z, Dlamini Z. MaRNA marefu asina makodhi (LncRNAs), ma genomics egomarara rehutachiona uye zviitiko zvisina kujairika zvekubatanidza: mhedzisiro yekurapa. AM J CANCER RES [chinyorwa chemagazini; ongororo]. 2021 01/20/2021;11(3):866–83.
Wang J, Chen P, Zhang Y, Ding J, Yang Y, Li H. 11-Kuzivikanwa kwezviratidzo zve lncRNA zvine chekuita nekufanotaura kwekenza ye endometrial. Zvakaitwa nesainzi [chinyorwa chemagazini]. 2021 2021-01-01;104(1):311977089.
Jiang S, Ren H, Liu S, Lu Z, Xu A, Qin S, nevamwe. Kuongororwa kwakakwana kwemajini ekufanotaura eRNA-binding protein uye mishonga inodiwa mu papillary cell renal cell carcinoma. pregen. [Journal article]. 2021 01/20/2021;12:627508.
Li X, Chen J, Yu Q, Huang X, Liu Z, Wang X, nevamwe. Hunhu hweRNA refu isina coding ine chekuita ne autophagy hunoratidza kufanotaura kwekenza yemazamu. pregen. [Journal article]. 2021 01/20/2021;12:569318.
Zhou M, Zhang Z, Zhao X, Bao S, Cheng L, Sun J. Siginecha ye6 yeLNCRNA ine chekuita neimmune system inovandudza kufambira mberi kwechirwere mu glioblastoma multiforme. MOL Neurobiology. [Nyaya yeJournal]. 2018 01.05.2018;55(5):3684–97.
Wu B, Wang Q, Fei J, Bao Y, Wang X, Song Z, nevamwe. Chiratidzo chitsva che tri-lncRNA chinofanotaura kupona kwevarwere vane kenza yepancreatic. VAIMIRIRI VE ONKOL. [Chinyorwa cheJournal]. 2018 12/01/2018;40(6):3427–37.
Luo C, Lin K, Hu C, Zhu X, Zhu J, Zhu Z. LINC01094 inokurudzira kufambira mberi kwegomarara repancreas nekudzora kuratidzwa kweLIN28B uye nzira yePI3K/AKT kuburikidza nesponged miR-577. Mol Therapeutics - Nucleic acids. 2021;26:523–35.
Lin J, Zhai X, Zou S, Xu Z, Zhang J, Jiang L, nevamwe. Mhinduro dzakanaka pakati pelncRNA FLVCR1-AS1 neKLF10 dzinogona kudzivirira kufambira mberi kwekenza yepancreatic kuburikidza nenzira yePTEN/AKT. J EXP Clin Cancer Res. 2021;40(1).
Zhou X, Liu X, Zeng X, Wu D, Liu L. Kuzivikanwa kwemajini gumi nematatu anofanotaura kupona kwese mukenza yeropa. Biosci Rep [chinyorwa chemagazini]. 2021 04/09/2021.
Nguva yekutumira: Gunyana-22-2023