Umhlaza wePancreatic lelinye lawona mathumba abulalayo emhlabeni anesimo esibi.Ke ngoko, imodeli echanekileyo yokuxela kwangaphambili iyafuneka ukuchonga izigulane ezisengozini enkulu yomhlaza we-pancreatic ukulungelelanisa unyango kunye nokuphucula i-prognosis yezi zigulana.
Sifumene iCancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq data kwi-database ye-UCSC Xena, echonge i-lncRNAs enxulumene nomzimba (irlncRNAs) ngohlalutyo lokulungelelanisa, kwaye ichonge ukungafani phakathi kwe-TCGA kunye ne-pancreatic adenocarcinoma tissues.I-DEirlncRNA) esuka kwi-TCGA kunye ne-genotype tissue expression (GTEx) yezicubu ze-pancreatic.Olunye uhlalutyo olungaguquguqukiyo kunye ne-lasso regression lwenziwa ukuze kwakhiwe imodeli yesignesha ye-prognostic.Emva koko sibala indawo ephantsi kwegophe kwaye sinqume ixabiso elifanelekileyo le-cutoff yokuchonga izigulane ezine-pancreatic adenocarcinoma ephezulu kunye nephantsi.Ukuthelekisa iimpawu zeklinikhi, ukungena kwe-immune cell, i-immunosuppressive microenvironment, kunye nokumelana ne-chemotherapy kwizigulane ezinomhlaza we-pancreatic ophezulu kunye nomngcipheko ophantsi.
Sichonge izibini ze-DEirlncRNA ezingama-20 kunye nezigulane zamaqela ngokwexabiso elifanelekileyo lokunqunyulwa.Sibonise ukuba imodeli yethu yesiginitsha ye-prognostic inentsebenzo ebalulekileyo ekuqikeleleni i-prognosis yezigulane ezine-PAAD.I-AUC ye-curve ye-ROC yi-0.905 ye-1-year forecast, i-0.942 ye-2-year forecast, kunye ne-0.966 ye-3-year forecast.Izigulana ezisemngciphekweni omkhulu zinezinga eliphantsi lokusinda kunye neempawu ezibi kakhulu zeklinikhi.Sikwabonise ukuba izigulana ezisemngciphekweni omkhulu zi-immunosuppressed kwaye zinokukhula ukuxhathisa kunyango lwamajoni omzimba.Ukuphononongwa kwamachiza e-anticancer afana ne-paclitaxel, i-sorafenib, kunye ne-erlotinib esekelwe kwizixhobo zokuqikelela ukubala zingaba zifanelekile kwizigulane ezinomngcipheko ophezulu we-PAAD.
Ngokubanzi, uphononongo lwethu luseke imodeli entsha yomngcipheko we-prognostic esekwe kwi-irlncRNA edibeneyo, ebonisa ixabiso elithembisayo le-prognostic kwizigulana ezinomhlaza wepancreatic.Imodeli yethu yomngcipheko we-prognostic inokunceda ukwahlula izigulane ezine-PAAD ezilungele unyango lwezonyango.
Umhlaza wePancreatic lithumba eliyingozi elinezinga eliphantsi lokusinda leminyaka emihlanu kunye nenqanaba eliphezulu.Ngexesha lokuxilonga, izigulane ezininzi sele zikwinqanaba eliphezulu.Kumxholo we-COVID-19 ubhubhane, oogqirha kunye nabongikazi baphantsi koxinzelelo olukhulu xa benyanga abaguli abanomhlaza wepancreatic, kwaye iintsapho zezigulana zikwajongene noxinzelelo oluninzi xa zisenza izigqibo zonyango [1, 2].Nangona intuthuko enkulu yenziwe kunyango lwe-DOADs, njengonyango lwe-neoadjuvant, utyando, unyango lwe-radiation, i-chemotherapy, unyango olujoliswe kuyo, kunye ne-immune checkpoint inhibitors (ICIs), kuphela malunga ne-9% yezigulane ezisinda kwiminyaka emihlanu emva kokuxilongwa [3] ].], 4].Ngenxa yokuba iimpawu zokuqala ze-pancreatic adenocarcinoma azibonakali, izigulane zidla ngokufunyaniswa zine-metastases kwinqanaba eliphezulu [5].Ke ngoko, kwisigulana esinikiweyo, unyango olubanzi lomntu ngamnye kufuneka luvavanye iingenelo kunye nokungalunganga kuzo zonke iindlela zonyango, kungekuphela nje ukolula ukusinda, kodwa nokuphucula umgangatho wobomi [6].Ke ngoko, imodeli esebenzayo yokuxela kwangaphambili iyimfuneko ukuvavanya ngokuchanekileyo i-prognosis yesigulane [7].Ngaloo ndlela, unyango olufanelekileyo lunokukhethwa ukulinganisela ukusinda kunye nomgangatho wobomi bezigulane ezine-PAAD.
Ukungazinzi kakuhle kwe-PAAD kubangelwa ikakhulu kukuchasa amayeza echemotherapy.Kwiminyaka yakutshanje, i-immune checkpoint inhibitors isetyenziswe ngokubanzi kunyango lwamathumba aqinileyo [8].Nangona kunjalo, ukusetyenziswa kwe-ICIs kumhlaza we-pancreatic kunqabile ukuba kuphumelele [9].Ngoko ke, kubalulekile ukuchonga izigulane ezinokuzuza kunyango lwe-ICI.
I-RNA ende engeyiyo ikhowudi (lncRNA) luhlobo lwe-RNA engabhaliyo enemibhalo>200 nucleotides.I-LncRNAs zixhaphakile kwaye zenza malunga ne-80% ye-transcriptome yomntu [10].Umzimba omkhulu womsebenzi ubonise ukuba i-lncRNA-based prognostic models inokuqikelela ngokufanelekileyo i-prognosis yesigulane [11, 12].Ngokomzekelo, ii-lncRNA ezi-18 ezinxulumene ne-autophagy zichongiwe ukuba zenze usayino lwe-prognostic kumhlaza webele [13].Ezinye ii-lncRNA ezintandathu ezinxulumene nomzimba ziye zasetyenziselwa ukuseka iimpawu ze-glioma [14].
Kumhlaza wepancreatic, ezinye iiphononongo ziye zaseka utyikityo olusekwe kwi-lncRNA ukuqikelela uqikelelo lwesigulana.Isignesha ye-3-lncRNA yasungulwa kwi-pancreatic adenocarcinoma kunye nommandla ophantsi kwe-ROC curve (AUC) ye-0.742 kuphela kunye nokusinda ngokubanzi (OS) ye-3 iminyaka [15].Ukongeza, amaxabiso enkcazo ye-lncRNA ayahluka phakathi kweegenomes ezahlukeneyo, iifomathi ezahlukeneyo zedatha, kunye nezigulana ezahlukeneyo, kwaye ukusebenza kwemodeli yokuqikelela akuzinzanga.Ngoko ke, sisebenzisa i-algorithm yokulinganisa inoveli, ukubhanqa kunye nokuphindaphinda, ukuvelisa i-lncRNA (irlncRNA) enxulumene nokunganyangeki (irlncRNA) isayinwe ukudala imodeli echanekileyo kunye nezinzile yokuxela kwangaphambili [8].
Idatha ye-RNAseq eqhelekileyo (FPKM) kunye nomhlaza we-pancreatic kliniki i-TCGA kunye ne-genotype tissue expression (GTEx) idatha ifunyenwe kwi-database ye-UCSC XENA (https://xenabrowser.net/datapages/).Iifayile ze-GTF zifunyenwe kwiziko ledatha le-Ensemble ( http://asia.ensembl.org ) kwaye zisetyenziselwa ukukhupha iiprofayili zokubonisa i-lncRNA kwi-RNAseq.Sikhuphele ijene yemfuza enxulumene nokugonyeka kwiziko ledatha le-ImmPort (http://www.immport.org) kwaye sachonga ii-lncRNAs ezinxulumene nokugonyeka (irlncRNAs) sisebenzisa uhlalutyo lolungelelwaniso (p <0.001, r > 0.4).Ukuchongwa kwee-irlncRNAs ezichazwe ngokwahlukileyo (DEirlncRNAs) ngokunqumla i-irlncRNAs kunye nee-lncRNA ezichazwe ngokwahlukileyo ezifunyenwe kuvimba wedatha weGEPIA2 (http://gepia2.cancer-pku.cn/#index) kwiqela le-TCGA-PAAD (|logFC| > 1 kunye neFDR ) <0.05).
Le ndlela iye yaxelwa ngaphambili [8].Ngokukodwa, sakha i-X ukuze ithathe indawo ye-lncRNA A edibeneyo kunye ne-lncRNA B. Xa ixabiso lenkcazo ye-lncRNA A iphezulu kunexabiso lenkcazo ye-lncRNA B, u-X uchazwa njengo-1, ngaphandle koko u-X uchazwa njengo-0. Ngoko ke, sinokufumana i-matrix ye-0 okanye - 1. I-axis ethe nkqo ye-matrix imele isampuli nganye, kwaye i-axis ethe tye imele i-DEirlncRNA nganye iperi ngexabiso le-0 okanye i-1.
Uhlalutyo olungaguqukiyo lokuhlehla olulandelwa yi-Lasso regression lusetyenziselwe ukuhluza izibini ze-DEirlncRNA ze-prognostic.Uhlalutyo lwe-lasso regression lusetyenziswe i-10-fold cross-validation ephindaphindiweyo ngamaxesha e-1000 (p <0.05), kunye ne-1000 random stimuli per run.Xa i-frequency ye-DEirlncRNA nganye ibini idlula amaxesha angama-100 kwimijikelezo ye-1000, izibini ze-DEirlncRNA zakhethwa ukwakha imodeli yengozi ye-prognostic.Emva koko sasebenzisa ijika le-AUC ukufumana elona xabiso lifanelekileyo lokunqunyulwa kokuhlela izigulane ze-PAAD zibe ngamaqela asemngciphekweni ophezulu naphantsi.Ixabiso le-AUC lemodeli nganye libalwe kwaye licwangciswe njengegophe.Ukuba ijika lifikelela kwinqanaba eliphezulu elibonisa ixabiso eliphezulu le-AUC, inkqubo yokubala iyayeka kwaye imodeli ithathwa njengomviwa ongcono kakhulu.I-1-, i-3- kunye ne-5 yeminyaka yeemodeli ze-curve ze-ROC zakhiwe.Uhlalutyo lwe-univariate kunye ne-multivariate regression lusetyenziselwa ukuvavanya ukusebenza okuzimeleyo okuqikelelwayo komzekelo wengozi ye-prognostic.
Sebenzisa izixhobo ezisixhenxe zokufunda amanqanaba okungena kwe-immune cell, kubandakanywa i-XCELL, i-TIMER, i-QUANTISEQ, i-MCPCOUNTER, i-EPIC, i-CIBERSORT-ABS, kunye ne-CIBERSORT.Idatha yokungena kwiseli yamajoni omzimba yakhutshelwa kuvimba wedatha we-TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Umahluko kumxholo we-immune-infiltrating cellss between the high-and low-risk groups of the built model yahlalutywa kusetyenziswa i-Wilcoxon sign-rank test, iziphumo ziboniswa kwigrafu yesikwere.Uhlalutyo lolungelelwaniso lwe-Spearman lwenziwa ukuhlalutya ubudlelwane phakathi kwamanqaku omngcipheko kunye neeseli ezingena emzimbeni.Isiphumo solungelelwaniso somlinganiso siboniswa njengelollipop.Ukubaluleka kokubaluleka kubekwe kwi-p <0.05.Inkqubo yenziwa kusetyenziswa i-R package ggplot2.Ukuphonononga ubudlelwane phakathi kwemodeli kunye namanqanaba okuchazwa kofuzo ahambelana nezinga lokungena kweseli yomzimba yokuzikhusela, senze iphakheji ye-ggstatsplot kunye nokubonwa kweploti yeviolin.
Ukuvavanya iipateni zonyango lomhlaza we-pancreatic, sibale i-IC50 yamachiza aqhelekileyo asetyenziswa ngamachiza e-chemotherapy kwiqela le-TCGA-PAAD.Ukwahluka kwi-half inhibitory concentrations (IC50) phakathi kwamaqela aphezulu kunye nomngcipheko ophantsi kwafaniswa kusetyenziswa uvavanyo lwe-Wilcoxon olusayinwe, kwaye iziphumo ziboniswa njengebhokisi yeebhokisi ezenziwe kusetyenziswa i-pRrophetic kunye ne-ggplot2 kwi-R. Zonke iindlela zihambelana nezikhokelo ezifanelekileyo kunye nemimiselo.
Ukuhamba komsebenzi wokufunda kwethu kuboniswe kuMzobo 1. Ukusebenzisa uhlalutyo lokulungelelanisa phakathi kwe-lncRNAs kunye neegenes ezinxulumene ne-immunity, sikhethe i-724 irlncRNAs kunye ne-p <0.01 kunye ne-r> 0.4.Ngokulandelayo sihlalutye ii-lncRNA ezichazwe ngokwahlukileyo zeGEPIA2 (Umfanekiso 2A).Iyonke i-223 irlncRNAs ibonakaliswe ngokwahlukileyo phakathi kwe-pancreatic adenocarcinoma kunye ne-pancreatic tishu eziqhelekileyo (|logFC| > 1, FDR <0.05), ezibizwa ngokuba yi-DEirlncRNAs.
Ukwakhiwa kweemodeli zomngcipheko oqikelelwayo.(A) Iploti yentaba-mlilo yee-lncRNA ezichazwe ngokwahlukileyo.(B) Ukuhanjiswa kwe-lasso coefficients kwi-20 DEirlncRNA pairs.(C) Ukwahluka okunokwenzeka okuyingxenye ye-LASSO coefficient distribution.(D) Indawo yehlathi ebonisa uhlalutyo olungaguqukiyo lwe-regression of 20 DEirlncRNA pairs.
Ngokulandelayo sakhe i-matrix eyi-0 okanye enye ngokudibanisa ii-DEirlncRNA ezingama-223.Iyonke ngama-13,687 izibini zeDEirlncRNA zachongwa.Emva kokuhlalutya kwe-univariate kunye ne-lasso regression, i-20 i-DEirlncRNA izibini zaye zavavanywa ekugqibeleni ukwakha imodeli yomngcipheko we-prognostic (Umfanekiso 2B-D).Ngokusekelwe kwiziphumo zeLasso kunye nokuhlalutya okuphindaphindiweyo, sibale inqaku lomngcipheko kwisigulane ngasinye kwiqela le-TCGA-PAAD (Itheyibhile 1).Ngokusekelwe kwiziphumo zohlalutyo lwe-lasso regression, sibale umngcipheko womngcipheko kwisigulane ngasinye kwiqela le-TCGA-PAAD.I-AUC ye-curve ye-ROC yayiyi-0.905 ye-1-year risk model prediction, i-0.942 ye-2-year prediction, kunye ne-0.966 ye-3-year prediction (Umfanekiso 3A-B).Sibeka ixabiso elifanelekileyo le-cutoff ye-3.105, i-stratify izigulane ze-TCGA-PAAD zeqela zibe ngamaqela anobungozi obuphezulu kunye nomngcipheko ophantsi, kwaye sicwangcisa iziphumo zokusinda kunye nokunikezelwa kwamanqaku omngcipheko kwisigulane ngasinye (Umfanekiso 3C-E).Uhlalutyo lwe-Kaplan-Meier lubonise ukuba ukusinda kwezigulane ze-PAAD kwiqela elinobungozi obuphezulu kwakuphantsi kakhulu kunezigulane ezikwiqela eliphantsi (p <0.001) (Umfanekiso 3F).
Ukunyaniseka kweemodeli zomngcipheko we-prognostic.(A) I-ROC yemodeli yomngcipheko we-prognostic.(B) I-1-, i-2-, kunye ne-3 yeminyaka ye-ROC yeemodeli zomngcipheko we-prognostic.(C) I-ROC yemodeli yomngcipheko we-prognostic.Ibonisa eyona ndawo ifanelekileyo yokunqunyulwa.(DE) Ukusasazwa kwemeko yokusinda (D) kunye namanqaku omngcipheko (E).(F) Uhlalutyo lwe-Kaplan-Meier lwezigulane ze-PAAD kumaqela aphezulu kunye nomngcipheko ophantsi.
Siphinde savavanya umahluko kumanqaku omngcipheko ngeempawu zeklinikhi.Umzobo we-strip (Umfanekiso 4A) ubonisa ubudlelwane phakathi kweempawu zeklinikhi kunye namanqaku omngcipheko.Ngokukodwa, izigulane ezikhulileyo zinemingcipheko ephezulu (Figure 4B).Ukongezelela, izigulane ezinesigaba se-II zineengozi eziphezulu zengozi kunezigulane ezinenqanaba I (Figure 4C).Ngokubhekiselele kwibakala le-tumor kwizigulane ze-PAAD, izigulane ze-3 zebakala zazinamanqaku aphezulu engozi kune-grade 1 kunye ne-2 yezigulane (Figure 4D).Saphinda senza uhlalutyo lwe-univariate kunye ne-multivariate regression kwaye sabonisa ukuba amanqaku omngcipheko (p <0.001) kunye nobudala (p = 0.045) yayiziimeko ezizimeleyo ze-prognostic kwizigulane ezine-PAAD (Umfanekiso 5A-B).Ijika le-ROC libonise ukuba amanqaku omngcipheko ayephezulu kunezinye iimpawu zeklinikhi ekuqikeleleni i-1-, i-2-, kunye ne-3 iminyaka yokuphila kwezigulane ezine-PAAD (Umfanekiso 5C-E).
Iimpawu zeklinikhi yeemodeli zengozi ye-prognostic.I-Histogram (A) ibonisa (B) ubudala, (C) isigaba sethumba, (D) ibakala lethumba, inqaku lomngcipheko, kunye nesini sezigulane kwiqela le-TCGA-PAAD.**p <0.01
Uhlalutyo oluzimeleyo lokuxela kwangaphambili kweemodeli zengozi ye-prognostic.(AB) I-Univariate (A) kunye ne-multivariate (B) i-regression ihlalutya imizekelo yengozi ye-prognostic kunye neempawu zeklinikhi.(CE) I-1-, i-2-, kunye ne-3 yeminyaka ye-ROC yeemodeli zengozi ye-prognostic kunye neempawu zeklinikhi
Ke ngoko, sivavanye ubudlelwane phakathi kwexesha kunye namanqaku omngcipheko.Sifumene ukuba amanqaku omngcipheko kwizigulane ze-PAAD adityaniswe ngokungafaniyo kunye neeseli ze-CD8 + T kunye neeseli ze-NK (Umfanekiso 6A), ebonisa ukunyanzeliswa komsebenzi we-immune kwiqela elinobungozi obukhulu.Siphinde savavanya umahluko kwi-immune cell infiltration phakathi kwamaqela aphezulu kunye nomngcipheko ophantsi kwaye wafumana iziphumo ezifanayo (Umfanekiso 7).Kwakukho ukungena okuncinci kweeseli ze-CD8 + T kunye neeseli ze-NK kwiqela elisemngciphekweni omkhulu.Kwiminyaka yakutshanje, i-immune checkpoint inhibitors (ICIs) isetyenziswe ngokubanzi kunyango lwamathumba aqinileyo.Nangona kunjalo, ukusetyenziswa kwe-ICIs kumhlaza we-pancreatic kunqabile ukuba kuphumelele.Ke ngoko, siye savavanya ukubonakaliswa kofuzo lwe-immune checkpoint kumaqela asemngciphekweni omkhulu naphantsi.Sifumene ukuba i-CTLA-4 kunye ne-CD161 (KLRB1) yayigqithise ngokugqithiseleyo kwiqela elinomngcipheko ophantsi (Umfanekiso 6B-G), ebonisa ukuba izigulane ze-PAAD kwiqela elinomngcipheko ophantsi zinokuthi zibe novelwano kwi-ICI.
Uhlalutyo lonxulumano lwemodeli yomngcipheko we-prognostic kunye nokungena kwe-immune cell cell.(A) Unxulumano phakathi kwemodeli yomngcipheko we-prognostic kunye nokungena kwe-immune cell cell.(BG) Ibonisa ukubonakaliswa kofuzo kumaqela aphezulu kunye nomngcipheko ophantsi.(HK) Amaxabiso e-IC50 kumachiza athile e-anticancer kumaqela asemngciphekweni omkhulu naphantsi.*p <0.05, **p <0.01, ns = ayibalulekanga
Siphinde savavanya unxibelelwano phakathi kwamanqaku omngcipheko kunye neearhente eziqhelekileyo zechemotherapy kwiqela le-TCGA-PAAD.Sikhangele amachiza e-anticancer asetyenziswa ngokuqhelekileyo kumhlaza we-pancreatic kwaye sahlalutya umahluko kumaxabiso abo e-IC50 phakathi kwamaqela asemngciphekweni omkhulu naphantsi.Iziphumo zibonise ukuba ixabiso le-IC50 le-AZD.2281 (olaparib) laliphezulu kwiqela elinobungozi obuphezulu, ebonisa ukuba izigulane ze-PAAD kwiqela elinobungozi obuphezulu zingamelana nonyango lwe-AZD.2281 (Umfanekiso 6H).Ukongeza, amaxabiso e-IC50 e-paclitaxel, i-sorafenib, kunye ne-erlotinib ayephantsi kwiqela elisemngciphekweni omkhulu (Umfanekiso 6I-K).Siphinde sachonga iziyobisi ezingama-34 ze-anticancer ezinexabiso eliphezulu le-IC50 kwiqela elisemngciphekweni omkhulu kunye neziyobisi ezingama-34 ze-anticancer ezinexabiso eliphantsi le-IC50 kwiqela elisemngciphekweni omkhulu (Itheyibhile 2).
Ayinakuphikiswa into yokuba ii-lncRNAs, ii-mRNAs, kunye nee-miRNAs zikho ngokubanzi kwaye zidlala indima ebalulekileyo kuphuhliso lomhlaza.Kukho ubungqina obaneleyo obuxhasa indima ebalulekileyo ye-mRNA okanye i-miRNA ekuqikeleleni ukusinda ngokubanzi kwiintlobo ezininzi zomhlaza.Ngaphandle kwamathandabuzo, iimodeli ezininzi zomngcipheko we-prognostic nazo zisekwe kwii-lncRNAs.Umzekelo, uLuo et al.Uphononongo lubonise ukuba i-LINC01094 idlala indima ephambili kwi-PC yokwanda kunye ne-metastasis, kunye nokubonakaliswa okuphezulu kwe-LINC01094 kubonisa ukusinda kakubi kwezigulane zomhlaza we-pancreatic [16].Uphononongo olunikezelwe nguLin et al.Uphononongo lubonise ukuba ukuthotywa kwe-lncRNA FLVCR1-AS1 inxulunyaniswa ne-prognosis embi kwizigulane zomhlaza we-pancreatic [17].Nangona kunjalo, ii-lncRNAs ezinxulumene nokugonyeka zixoxwa kancinci malunga nokuqikelela ukusinda okupheleleyo kwezigulana ezinomhlaza.Kutshanje, inani elikhulu lomsebenzi ligxile ekwakhiweni kweemodeli zengozi ye-prognostic ukuqikelela ukusinda kwezigulane ezinomhlaza kwaye ngaloo ndlela uhlengahlengiso iindlela zonyango [18, 19, 20].Kukho ukuqondwa okukhulayo kwendima ebalulekileyo yokungena komzimba ekuqaliseni umhlaza, ukuqhubela phambili, kunye nokuphendula kunyango olufana nechemotherapy.Izifundo ezininzi ziqinisekisile ukuba iiseli ze-immune ezingenayo i-tumor zidlala indima ebalulekileyo ekuphenduleni i-cytotoxic chemotherapy [21, 22, 23].I-tumor immune microenvironment yinto ebalulekileyo ekusindeni kwezigulane ze-tumor [24, 25].I-Immunotherapy, ngakumbi unyango lwe-ICI, lusetyenziswa ngokubanzi kunyango lwamathumba aqinileyo [26].Ufuzo olunxulumene nokhuselo lomzimba lusetyenziswa ngokubanzi ukwakha imifuziselo yomngcipheko we-prognostic.Umzekelo, uSu et al.Imodeli yengozi enxulumene nomzimba we-immune isekwe kwi-protein-coding genes ukuqikelela ukuxilongwa kwezigulane zomhlaza we-ovarian [27].Iijeni ezingezizo iikhowudi ezifana ne-lncRNA nazo zifanelekile ukwakha imodeli yengozi ye-prognostic [28, 29, 30].U-Luo et al wavavanya ii-lncRNA ezine ezinxulumene ne-immune kwaye wakhe imodeli eqikelelwayo yomngcipheko womhlaza womlomo wesibeleko [31].Khan et al.Itotali ye-32 ebhaliweyo echazwe ngokwahlukileyo ichongiwe, kwaye isekelwe kule nto, imodeli yokubikezela kunye ne-5 ebhaliweyo ebalulekileyo yasekwa, eyacetywayo njengesixhobo esicetyiswayo sokuqikelela ukugatywa kwe-biopsy-proven acute after transplantation [32].
Uninzi lwezi modeli zisekwe kumanqanaba embonakalo yemfuza, nokuba ziijini zeprotheyini ezikhowudayo okanye iigenes ezingakhowudiyo.Nangona kunjalo, uhlobo olufanayo lunokuba namaxabiso ahlukeneyo okuthetha kwiigenomes ezahlukeneyo, iifomathi zedatha nakwizigulane ezahlukeneyo, ezikhokelela kuqikelelo olungazinzanga kwiimodeli zokuqikelela.Kolu phononongo, sakhe imodeli efanelekileyo kunye neeperi ezimbini ze-lncRNAs, ezizimeleyo kwiimpawu ezichanekileyo zokubonisa.
Kolu phononongo, sichonge i-irlncRNA okokuqala ngohlalutyo lolungelelwaniso kunye nofuzo olunxulumene nokugonyeka.Sivavanye ii-DEirlncRNA ezingama-223 ngokuxutywa kunye nee-lncRNA ezivezwe ngokwahlukileyo.Okwesibini, sakhe i-matrix ye-0-okanye i-1 ngokusekelwe kwindlela yokubhanqa ye-DEirlncRNA epapashwe [31].Emva koko senza uhlalutyo lwe-univariate kunye ne-lasso regression ukuchonga izibini ze-DEirlncRNA ze-prognostic kunye nokwakha imodeli yomngcipheko oqikelelwayo.Siphinde sahlalutya unxibelelwano phakathi kwamanqaku omngcipheko kunye neempawu zeklinikhi kwizigulane ezine-PAAD.Sifumene ukuba imodeli yethu yomngcipheko we-prognostic, njengento ezimeleyo ye-prognostic factor kwizigulane ze-PAAD, inokwahlula ngokufanelekileyo izigulane eziphezulu kwizigulane eziphantsi kunye nezigulana eziphezulu kwizigulane eziphantsi.Ukongeza, amaxabiso e-AUC ejiko le-ROC yemodeli yomngcipheko we-prognostic yayiyi-0.905 yengqikelelo yonyaka omnye, i-0.942 yengqikelelo yeminyaka emi-2, kunye ne-0.966 yengqikelelo yeminyaka emi-3.
Abaphandi baxela ukuba izigulane ezine-CD8 + T ephezulu yokungena kwi-cell yayinovelwano ngakumbi kunyango lwe-ICI [33].Ukwanda kumxholo iiseli cytotoxic, iiseli CD56 NK, iiseli NK kunye CD8 + T iiseli kwithumba omzimba microenvironment inokuba sesinye sezizathu isiphumo ithumba suppressive [34].Izifundo zangaphambili zibonise ukuba amanqanaba aphezulu e-tumor-infiltrating CD4 (+) T kunye ne-CD8 (+) T yayinxulunyaniswa kakhulu nokuphila ixesha elide [35].Ukungeniswa kweseli ye-CD8 T engalunganga, umthwalo ophantsi we-neoantigen, kunye ne-immusuppressive tumor microenvironment ekhokelela ekuswelekeni kokuphendula kunyango lwe-ICI [36].Sifumene ukuba amanqaku omngcipheko adityaniswa kakubi kunye neeseli ze-CD8 + T kunye neeseli ze-NK, ezibonisa ukuba izigulane ezinobungozi obuphezulu zingase zingafaneleki unyango lwe-ICI kwaye zibe ne-prognosis embi kakhulu.
I-CD161 luphawu lweeseli zombulali wendalo (NK).I-CD8 + CD161 + i-CAR-transduced cell cell mediate ephuculweyo kwi-vivo antitumor efficacy in HER2 + pancreatic ductal adenocarcinoma xenograft models [37].I-immune checkpoint inhibitors ijolise kwi-cytotoxic T lymphocyte ehambelana neprotheyini ye-4 (CTLA-4) kunye neprotheni yokufa kweseli ecwangcisiweyo 1 (PD-1) / i-programmed cell death ligand 1 (PD-L1) iindlela kwaye inamandla amakhulu kwiindawo ezininzi.Ukubonakaliswa kwe-CTLA-4 kunye ne-CD161 (i-KLRB1) iphantsi kumaqela anobungozi obuphezulu, ebonisa ngakumbi ukuba izigulane ezinamanqaku aphezulu angenakukwazi ukufumana unyango lwe-ICI.[38]
Ukufumana iindlela zonyango ezifanelekileyo kwizigulane ezinomngcipheko ophezulu, sihlalutye iziyobisi ezahlukeneyo ze-anticancer kwaye safumanisa ukuba i-paclitaxel, i-sorafenib, kunye ne-erlotinib, esetyenziswa kakhulu kwizigulane ezine-PAAD, inokufaneleka kwizigulane ezinobungozi obuphezulu nge-PAAD.[33].U-Zhang et al ufumene ukuba ukuguqulwa kuyo nayiphi na indlela yokuphendula umonakalo we-DNA (DDR) kunokukhokelela kwi-prognosis embi kwizigulane zomhlaza we-prostate [39].Ulingo lwePancreatic Cancer Olaparib Ongoing (i-POLO) lubonise ukuba unyango lolondolozo kunye ne-olaparib yokusinda ixesha elide ngaphandle kokuqhubekela phambili xa kuthelekiswa ne-placebo emva komgca wokuqala we-chemotherapy esekwe kwiplatinam kwizigulana ezine-pancreatic ductal adenocarcinoma kunye ne-germline ye-BRCA1/2 utshintsho [40].Oku kunika ithemba elibalulekileyo lokuba iziphumo zonyango ziya kuphucula kakhulu kweli qela lezigulane.Kolu phononongo, ixabiso le-IC50 le-AZD.2281 (olaparib) laliphezulu kwiqela elinomngcipheko ophezulu, libonisa ukuba izigulane ze-PAAD kwiqela elinomngcipheko ophezulu zingamelana nonyango nge-AZD.2281.
Iimodeli zokuqikelela kolu phononongo zivelisa iziphumo ezilungileyo zokubikezela, kodwa zisekwe kuqikelelo lohlalutyo.Indlela yokuqinisekisa ezi ziphumo ngedatha yeklinikhi ngumbuzo obalulekileyo.I-Endoscopic finele aspiration aspiration ultrasonography (EUS-FNA) iye yaba yindlela efunekayo yokuxilonga izilonda eziqinileyo kunye ne-extrapancreatic pancreatic enobuzaza be-85% kunye nokucaciswa kwe-98% [41].Ukufika kweenaliti ze-EUS-fine-needle biopsy (EUS-FNB) zisekwe ikakhulu kwizinto eziluncedo ezingaphaya kwe-FNA, ezinjengokuchaneka okuphezulu koxilongo, ukufumana iisampulu ezigcina ubume be-histological, kwaye ngaloo ndlela kuveliswe izicubu zomzimba ezibaluleke kakhulu kuxilongo oluthile.ibala elikhethekileyo [42].Uphononongo olucwangcisiweyo loncwadi luqinisekisile ukuba iinaliti ze-FNB (ingakumbi i-22G) zibonisa ukusebenza okuphezulu ekuvuneni izicubu ezivela kwi-pancreatic mass [43].Ngokweklinikhi, kuphela inani elincinci lezigulane ezifanelekileyo zokuhlinzwa ngokukhawuleza, kwaye izigulane ezininzi zineethumba ezingasebenziyo ngexesha lokuxilongwa kokuqala.Kwinkqubo yeklinikhi, kuphela inxalenye encinci yezigulane ezifanelekileyo utyando olunzulu kuba izigulane ezininzi zineethumba ezingasebenziyo ngexesha lokuxilongwa kokuqala.Emva kokuqinisekiswa kwe-pathological yi-EUS-FNB kunye nezinye iindlela, unyango olusemgangathweni olungasebenzisi utyando olufana nechemotherapy ludla ngokukhethwa.Inkqubo yethu yophando olulandelayo kukuvavanya imodeli ye-prognostic yolu phononongo kumaqela otyando kunye nokungabikho kotyando ngohlalutyo lokubuyela emva.
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Ixesha lokuposa: Sep-22-2023