Umdlavuza we-pancreatic ungenye yezimila ezibulala kakhulu emhlabeni ezine-prognosis embi.Ngakho-ke, imodeli enembile yokubikezela iyadingeka ukukhomba iziguli ezisengozini enkulu yomdlavuza we-pancreatic ukuze ulungise ukwelashwa futhi uthuthukise ukubikezela kwalezi ziguli.
Sithole idatha ye-Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq kusizindalwazi se-UCSC Xena, sahlonza ama-lncRNA ahlobene nokuzivikela komzimba (irlncRNAs) ngokuhlaziywa kokuhlobana, futhi sathola umehluko phakathi kwe-TCGA nezicubu ezivamile ze-pancreatic adenocarcinoma.I-DEirlncRNA) evela ku-TCGA kanye ne-genotype tissue expression (GTEx) yezicubu ze-pancreatic.Ukuhlaziywa okwengeziwe kwe-univariate kanye ne-lasso regression kwenziwa ukuze kwakhiwe amamodeli wesiginesha okubikezelwa.Sabe sesibala indawo engaphansi kwejika futhi sanquma inani eliphelele lokunquma ukuhlonza iziguli ezine-pancreatic adenocarcinoma enobungozi obukhulu nephansi.Ukuze uqhathanise izici zomtholampilo, ukungena kwamangqamuzana omzimba omzimba, i-immune immunosuppressive microenvironment, kanye nokumelana ne-chemotherapy ezigulini ezinomdlavuza we-pancreatic oyingozi kakhulu futhi ophansi.
Sihlonze amapheya angu-20 e-DEirlncRNA futhi sahlanganisa iziguli ngokwenani elifanele lokunqanyulwa.Sibonise ukuthi imodeli yethu yesiginesha yokubikezela inokusebenza okubalulekile ekubikezeleni ukubikezela kweziguli ezine-PAAD.I-AUC yejika le-ROC ingu-0.905 esibikezelweni sonyaka ongu-1, i-0.942 yesibikezelo seminyaka emi-2, kanye no-0.966 ngokwesibikezelo seminyaka emi-3.Iziguli ezisengozini enkulu zazinamazinga aphansi okusinda kanye nezici zomtholampilo ezimbi kakhulu.Siphinde sabonisa ukuthi iziguli ezisengozini enkulu amasosha omzimba futhi zingase zibe nokumelana ne-immunotherapy.Ukuhlolwa kwezidakamizwa ezilwa nomdlavuza njenge-paclitaxel, i-sorafenib, ne-erlotinib ngokusekelwe kumathuluzi okuqagela ngekhompyutha kungase kulungele iziguli ezisengozini enkulu nge-PAAD.
Sekukonke, ucwaningo lwethu lusungule imodeli entsha yengozi yokubikezela esekelwe ku-irlncRNA ebhanqiwe, ebonise inani elithembisayo lokubikezela ezigulini ezinomdlavuza we-pancreatic.Imodeli yethu yokubikezela ingozi ingase isize ukuhlukanisa iziguli ezine-PAAD ezifanele ukwelashwa.
Umdlavuza we-pancreatic yisimila esiyingozi esinezinga eliphansi lokusinda leminyaka emihlanu kanye nebanga eliphakeme.Ngesikhathi sokuxilongwa, iziguli eziningi sezivele zisezingeni eliphezulu.Esimweni sobhubhane lwe-COVID-19, odokotela nabahlengikazi bangaphansi kwengcindezi enkulu lapho belapha iziguli ezinomdlavuza we-pancreatic, futhi imindeni yeziguli nayo ibhekana nezingcindezi eziningi lapho yenza izinqumo zokwelashwa [1, 2].Nakuba kuye kwenziwa intuthuko enkulu ekwelapheni ama-DOAD, njengokwelashwa kwe-neoadjuvant, ukuhlinzwa kabusha, ukwelapha ngemisebe, ukwelashwa ngamakhemikhali, ukwelashwa kwamangqamuzana okuhlosiwe, kanye ne-immune checkpoint inhibitors (ICIs), cishe i-9% yeziguli ezisinda eminyakeni emihlanu ngemuva kokuxilongwa [3. ].], 4].Ngenxa yokuthi izimpawu zokuqala ze-pancreatic adenocarcinoma azibonakali, iziguli zivame ukutholakala ukuthi zine-metastase esigabeni esithuthukisiwe.Ngakho-ke, esigulini esinikeziwe, ukwelashwa okuphelele komuntu ngamunye kufanele kukale izinzuzo nezinkinga zazo zonke izinketho zokwelashwa, hhayi nje ukwandisa isikhathi sokuphila, kodwa futhi nokwenza ngcono izinga lempilo [6].Ngakho-ke, imodeli esebenzayo yokubikezela iyadingeka ukuze kuhlolwe ngokunembile ukubikezela kwesiguli [7].Ngakho-ke, ukwelashwa okufanele kungakhethwa ukulinganisa ukusinda kanye nekhwalithi yempilo yeziguli ezine-PAAD.
Ukubikezelwa okungekuhle kwe-PAAD kubangelwa ikakhulukazi ukumelana nemithi yokwelapha ngamakhemikhali.Eminyakeni yamuva nje, ama-immune checkpoint inhibitors asetshenziswe kabanzi ekwelapheni izimila eziqinile [8].Kodwa-ke, ukusetshenziswa kwama-ICI kumdlavuza we-pancreatic akuvamile ukuphumelela [9].Ngakho-ke, kubalulekile ukukhomba iziguli ezingase zizuze ekwelashweni kwe-ICI.
I-RNA ende engakhohlisi (lncRNA) iwuhlobo lwe-RNA engafaki amakhodi enemibhalo >200 nucleotide.Ama-LncRNA asabalele futhi akha cishe ama-80% we-transcriptome yomuntu [10].Umsebenzi omkhulu ubonise ukuthi amamodeli asuselwa ku-lncRNA angabikezela ngempumelelo ukubikezela kwesiguli [11, 12].Isibonelo, ama-lncRNA ahlobene ne-autophagy angu-18 ahlonzwe ukuze akhiqize amasignesha okubikezela kumdlavuza webele [13].Amanye ama-lncRNA ayisithupha ahlobene nokuzivikela asetshenziswe ukusungula izici zokubikezela ze-glioma [14].
Kumdlavuza we-pancreatic, ezinye izifundo zenze amasiginesha asuselwa ku-lncRNA ukuze abikezele ukubikezelwa kwesiguli.Isiginesha ye-3-lncRNA yasungulwa ku-pancreatic adenocarcinoma enendawo engaphansi kwe-ROC curve (AUC) engu-0.742 kuphela kanye nokusinda okuphelele (OS) kweminyaka emi-3 [15].Ngaphezu kwalokho, amanani enkulumo ye-lncRNA ayahluka phakathi kwama-genome ahlukene, amafomethi wedatha ahlukene, neziguli ezihlukene, futhi ukusebenza kwemodeli yokubikezela akuzinzile.Ngakho-ke, sisebenzisa i-algorithm yenoveli yokumodela, ukubhanqa nokuphindaphinda, ukuze sikhiqize amasiginesha ahlobene nokuvikeleka kwe-lncRNA (irlncRNA) ukuze sakhe imodeli yokubikezela enembe kakhudlwana futhi ezinzile [8].
Idatha ye-RNAseq evamile (FPKM) kanye ne-TCGA yomdlavuza we-pancreatic kliniki kanye nedatha ye-genotype tissue expression (GTEx) itholwe kusizindalwazi se-UCSC XENA ( https://xenabrowser.net/datapages/ ).Amafayela e-GTF atholwe kusizindalwazi se-Ensemble ( http://asia.ensembl.org ) futhi asetshenziselwe ukukhipha amaphrofayili esisho se-lncRNA ku-RNAseq.Silande izakhi zofuzo ezihlobene nokuvikeleka kusizindalwazi se-ImmPort (http://www.immport.org) futhi sahlonza ama-lncRNA ahlobene nokuvikeleka (irlncRNAs) sisebenzisa ukuhlaziywa kokuhlobana (p <0.001, r > 0.4).Ukuhlonzwa kwe-irlncRNAs evezwe ngokuhlukile (DEirlncRNAs) ngokweqa ama-irlncRNA kanye nama-lncRNA avezwe ngokwehlukana atholwe kusizindalwazi se-GEPIA2 (http://gepia2.cancer-pku.cn/#index) kuqoqo le-TCGA-PAAD (|logFC| > 1 kanye ne-FDR <0.05).
Le ndlela ibikwe ngaphambilini [8].Ngokukhethekile, sakha u-X ukuze amiselele i-lncRNA A ebhanqiwe kanye ne-lncRNA B. Uma inani lesisho elithi lncRNA A lingaphezulu kwevelu yenkulumo ye-lncRNA B, u-X uchazwa ngokuthi 1, ngaphandle kwalokho u-X uchazwa ngokuthi 0. Ngakho-ke, singathola i-matrix ka-0 noma – 1. I-eksisi eme mpo ye-matrix imelela isampula ngayinye, futhi i-eksisi evundlile imelela ipheya ngayinye ye-DEirlncRNA enenani elingu-0 noma u-1.
Ukuhlaziywa kokuhlehla okungaguquki okulandelwa ukuhlehla kwe-Lasso kwasetshenziswa ukuze kuhlolwe amapheya e-DEirlncRNA okubikezelwa.Ukuhlaziywa kwe-lasso regression kusetshenziswe ukuqinisekiswa kwe-cross-fold 10 okuphindaphindiwe izikhathi ezingu-1000 (p <0.05), nge-stimuli engahleliwe engu-1000 ngokugijima ngakunye.Lapho imvamisa yokubhangqa ngakunye kwe-DEirlncRNA idlula izikhathi eziyi-100 emijikelezweni engu-1000, amapheya e-DEirlncRNA akhethwa ukuze akhe imodeli yengozi ebikezelwayo.Sibe sesisebenzisa ijika le-AUC ukuze sithole inani eliphelele lokunqamula ukuhlukanisa iziguli ze-PAAD ngamaqembu anobungozi obukhulu nobuncane.Inani le-AUC lemodeli ngayinye nalo labalwa futhi lahlelwa njengejika.Uma ijika lifinyelela iphuzu eliphakeme kakhulu elibonisa inani eliphakeme le-AUC, inqubo yokubala iyama futhi imodeli ibhekwa njengekhandidethi elingcono kakhulu.1-, 3- kanye ne-5-year ROC curve models zakhiwe.Ukuhlaziywa kokuhlehla kwe-univariate kanye ne-multivariate kwasetshenziselwa ukuhlola ukusebenza okuzimele kokubikezela kwemodeli yengozi yokubikezela.
Sebenzisa amathuluzi ayisikhombisa ukuze ufunde amazinga okungena kwamaseli omzimba, okuhlanganisa i-XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, ne-CIBERSORT.Idatha yokungeniswa kwamaseli amasosha omzimba yalandwa kusukela kusizindalwazi se-TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Umehluko kokuqukethwe kwamaseli angena ngokuzivikela omzimba phakathi kwamaqembu anengcuphe ephezulu nephansi yemodeli eyakhiwe uye wahlaziywa kusetshenziswa ukuhlolwa kwezinga elisayiniwe le-Wilcoxon, imiphumela iboniswa kugrafu eyisikwele.Ukuhlaziywa kokuhlobana kwe-Spearman kwenziwa ukuze kuhlaziywe ubudlelwano phakathi kwamanani wamaphuzu engozi namaseli angena emzimbeni.I-coefficient yokuxhumana ewumphumela iboniswa njengelolipop.Umkhawulo wokubaluleka wawubekwe ku-p <0.05.Inqubo yenziwa kusetshenziswa i-R package ggplot2.Ukuhlola ubudlelwano phakathi kwemodeli namaleveli esisho sofuzo ahlobene nezinga lokungena kwamaseli omzimba, senze iphakheji ye-ggstatsplot kanye nokuboniswa kwesakhiwo sevayolini.
Ukuze sihlole amaphethini okwelapha emtholampilo omdlavuza we-pancreatic, sibale i-IC50 yezidakamizwa ezivame ukusetshenziswa ngamakhemikhali eqenjini le-TCGA-PAAD.Umehluko ekugxilweni kwe-half inhibitory concentrations (IC50) phakathi kwamaqembu engcuphe ephezulu kanye nephansi uqhathaniswe kusetshenziswa isivivinyo sezinga elisayiniwe le-Wilcoxon, futhi imiphumela iboniswa njengama-boxplots akhiqizwe kusetshenziswa i-pRrophetic ne-ggplot2 ku-R. Zonke izindlela zithobela imihlahlandlela efanele nezinkambiso.
Ukuhamba komsebenzi wocwaningo lwethu kuboniswe kuMfanekiso 1. Ukusebenzisa ukuhlaziywa kokuhlobana phakathi kwe-lncRNA nezakhi zofuzo ezihlobene nokuzivikela komzimba, sikhethe i-724 irlncRNAs nge-p <0.01 kanye ne-r> 0.4.Ngokulandelayo sihlaziye ama-lncRNA avezwe ngokuhlukile we-GEPIA2 (Umfanekiso 2A).Ingqikithi yama-irlncRNA angu-223 abonakaliswe ngokwehlukana phakathi kwe-pancreatic adenocarcinoma kanye nezicubu ze-pancreatic ezivamile (|logFC| > 1, FDR <0.05), eziqanjwe ngokuthi ama-DEirlncRNAs.
Ukwakhiwa kwamamodeli ezingozi ezibikezelayo.(A) Isakhiwo sentabamlilo ye-lncRNA evezwe ngokuhlukile.(B) Ukusatshalaliswa kwama-coefficient e-lasso ngamapheya angu-20 e-DEirlncRNA.(C) Ukuhluka okungaba khona kokusatshalaliswa kwe-coefficient ye-LASSO.(D) Isakhiwo sehlathi esibonisa ukuhlaziywa kokuhlehla okungaguquki kwamapheya angu-20 e-DEirlncRNA.
Ngokulandelayo sakhe i-matrix engu-0 noma engu-1 ngokumatanisa ama-DEirlncRNA angu-223.Isamba samapheya e-DEirlncRNA ayi-13,687 ahlonziwe.Ngemuva kokuhlaziywa kwe-univariate kanye ne-lasso regression, amapheya angama-20 e-DEirlncRNA ahlolwe ekugcineni ukuze akhe imodeli yengozi yokubikezela (Umfanekiso 2B-D).Ngokusekelwe emiphumeleni ye-Lasso nokuhlaziya okuningi kokuhlehla, sibale isikolo sengozi yesiguli ngasinye kuqoqo le-TCGA-PAAD (Ithebula 1).Ngokusekelwe emiphumeleni yokuhlaziywa kokuhlehla kwe-lasso, sibale isikolo sengozi yesiguli ngasinye kuqoqo le-TCGA-PAAD.I-AUC yejika le-ROC yayingu-0.905 yokubikezela imodeli yengozi yonyaka ongu-1, i-0.942 yokubikezela kweminyaka emi-2, kanye no-0.966 yokubikezela kweminyaka emi-3 (Umfanekiso 3A-B).Setha inani eliphelele lokunqanyulwa kwe-3.105, sahlukanisa iziguli zeqembu le-TCGA-PAAD zaba amaqembu asengozini enkulu nephansi, futhi sahlela imiphumela yokusinda nokusatshalaliswa kwamaphuzu engcuphe esigulini ngasinye (Umfanekiso 3C-E).Ukuhlaziywa kwe-Kaplan-Meier kubonise ukuthi ukusinda kweziguli ze-PAAD eqenjini eliyingozi kakhulu kwakuphansi kakhulu kuneziguli eziseqenjini elinobungozi obuphansi (p <0.001) (Umfanekiso 3F).
Ukuba semthethweni kwamamodeli engcuphe yokubikezela.(A) I-ROC yemodeli yengozi yokubikezela.(B) 1-, 2-, kanye ne-3-year ROC amamodeli engcuphe yokubikezela.(C) I-ROC yemodeli yengozi yokubikezela.Ibonisa iphuzu elilungile lokusika.(DE) Ukusatshalaliswa kwesimo sokusinda (D) kanye nezikolo zobungozi (E).(F) Ukuhlaziywa kwe-Kaplan-Meier kweziguli ze-PAAD emaqenjini aphezulu naphansi engozini.
Siphinde sahlola umehluko kuzikolo ezinobungozi ngezici zomtholampilo.Isakhiwo se-strip (Umfanekiso 4A) sibonisa ubudlelwane phakathi kwezici zomtholampilo kanye nezikolo zengozi.Ikakhulukazi, iziguli ezindala zazinamaphuzu aphezulu engozini (Umfanekiso 4B).Ukwengeza, iziguli ezinesiteji II zazinamaphuzu aphezulu engozini kuneziguli ezinesiteji I (Figure 4C).Mayelana nebanga lesimila ezigulini ze-PAAD, iziguli zebanga lesi-3 zazinamaphuzu aphezulu engozini kuneziguli zebanga loku-1 nelesi-2 (Umfanekiso 4D).Siphinde senza ukuhlaziya okungaguquguquki nokwehliswayo okuhlukahlukene futhi sabonisa ukuthi amaphuzu engcuphe (p <0.001) kanye nobudala (p = 0.045) kwakuyizici ezizimele zokubikezela ezigulini ezine-PAAD (Umfanekiso 5A-B).Ijika le-ROC libonise ukuthi amaphuzu engozi ayephakeme kunezinye izici zomtholampilo ekubikezeleni i-1-, 2-, kanye ne-3 yeminyaka yokusinda kweziguli ezine-PAAD (Umfanekiso 5C-E).
Izici zomtholampilo zamamodeli wengozi yokubikezela.I-Histogram (A) ibonisa (B) ubudala, (C) isigaba sesimila, (D) ibanga lesimila, isikolo sobungozi, nobulili beziguli eqenjini le-TCGA-PAAD.**p <0.01
Ukuhlaziywa okuzimele kokubikezela kwamamodeli wengozi yokubikezela.(AB) Univariate (A) kanye ne-multivariate (B) ihlaziya uhlaziyo lwamamodeli wengozi yokubikezela kanye nezici zomtholampilo.(CE) 1-, 2-, kanye neminyaka emi-3 ye-ROC yamamodeli wengozi yokubikezela kanye nezici zomtholampilo
Ngakho-ke, sihlole ubudlelwano phakathi kwesikhathi nezikolo ezinobungozi.Sithole ukuthi amaphuzu engcuphe ezigulini ze-PAAD ayehlotshaniswa ngokuphambene namaseli e-CD8+ T kanye namaseli e-NK (Umfanekiso 6A), okubonisa umsebenzi wokuzivikela omzimba ocindezelwe eqenjini elisengozini enkulu.Siphinde sahlola umehluko ekungeneni kwamangqamuzana omzimba phakathi kwamaqembu anobungozi obuphezulu naphansi futhi sathola imiphumela efanayo (Umfanekiso 7).Kube nokungenwa okuncane kwamaseli e-CD8+ T namaseli e-NK eqenjini elisengozini enkulu.Eminyakeni yamuva nje, i-immune checkpoint inhibitors (ICIs) isetshenziswe kabanzi ekwelapheni izimila eziqinile.Kodwa-ke, ukusetshenziswa kwama-ICI kumdlavuza we-pancreatic akuvamile ukuphumelela.Ngakho-ke, sihlole ukubonakaliswa kwezakhi zofuzo zokuhlola amasosha omzimba emaqenjini anobungozi obukhulu naphansi.Sithole ukuthi i-CTLA-4 kanye ne-CD161 (KLRB1) yayigxile kakhulu eqenjini elinobungozi obuphansi (Umfanekiso we-6B-G), okubonisa ukuthi iziguli ze-PAAD eqenjini elinobungozi obuphansi zingase zizwele ku-ICI.
Ukuhlaziywa kokuhlobana kwemodeli yengozi yokubikezela kanye nokungena kwamaseli omzimba omzimba.(A) Ukuhlobana phakathi kwemodeli yengcuphe yokubikezela nokungena kwamaseli omzimba.(BG) Ibonisa ukubonakaliswa kofuzo emaqenjini asengozini enkulu naphansi.(HK) Amanani e-IC50 ezidakamizwa ezithile ezilwa nomdlavuza emaqenjini asengozini enkulu naphansi.*p <0.05, **p <0.01, ns = akubalulekile
Siphinde sahlola ukuhlobana phakathi kwezikolo ezinobungozi kanye nama-ejenti avamile we-chemotherapy eqenjini le-TCGA-PAAD.Siseshe izidakamizwa ezivame ukusetshenziswa ezilwa nomdlavuza kumdlavuza we-pancreatic futhi sahlaziya umehluko kumanani awo e-IC50 phakathi kwamaqembu asengozini enkulu naphansi.Imiphumela ibonise ukuthi inani le-IC50 le-AZD.2281 (olaparib) laliphezulu eqenjini elinobungozi obukhulu, okubonisa ukuthi iziguli ze-PAAD eqenjini eliyingozi kakhulu zingase zimelane nokwelashwa kwe-AZD.2281 (Umfanekiso 6H).Ngaphezu kwalokho, amanani e-IC50 e-paclitaxel, i-sorafenib, ne-erlotinib ayephansi eqenjini elisengozini enkulu (Umfanekiso 6I-K).Siphinde sahlonza izidakamizwa ezilwa nomdlavuza ezingama-34 ezinamavelu e-IC50 aphezulu eqenjini elisengozini enkulu kanye nezidakamizwa ezilwa nomdlavuza ezingama-34 ezinamavelu e-IC50 aphansi eqenjini elisengozini enkulu (Ithebula 2).
Ngeke kuphikwe ukuthi ama-lncRNA, ama-mRNA, nama-miRNA akhona kabanzi futhi adlala indima ebalulekile ekuthuthukisweni komdlavuza.Kunobufakazi obanele obusekela indima ebalulekile ye-mRNA noma i-miRNA ekubikezeleni ukusinda okuphelele ezinhlotsheni ezimbalwa zomdlavuza.Ngokungangabazeki, amamodeli amaningi engcuphe yokubikezela nawo asekelwe kuma-lncRNA.Isibonelo, uLuo et al.Ucwaningo luye lwabonisa ukuthi i-LINC01094 idlala indima ebalulekile ekwandeni kwe-PC kanye ne-metastasis, futhi ukubonakaliswa okuphezulu kwe-LINC01094 kubonisa ukusinda okungalungile kweziguli ezinomdlavuza we-pancreatic [16].Ucwaningo olwethulwa uLin et al.Ucwaningo luye lwabonisa ukuthi ukwehliswa kwe-lncRNA FLVCR1-AS1 kuhlotshaniswa nokubikezelwa okungalungile kweziguli ezinomdlavuza we-pancreatic [17].Kodwa-ke, ama-lncRNA ahlobene nokuzivikela komzimba akuxoxwa kangako ngokubikezela ukusinda okuphelele kweziguli ezinomdlavuza.Muva nje, inani elikhulu lomsebenzi ligxile ekwakheni amamodeli engcuphe yokubikezela ukubikezela ukusinda kweziguli ezinomdlavuza futhi ngaleyo ndlela kulungiswe izindlela zokwelapha [18, 19, 20].Kukhona ukuqashelwa okukhulayo kwendima ebalulekile yokungena komzimba ekuqalisweni komdlavuza, ukuqhubeka, kanye nokusabela ekwelashweni okufana ne-chemotherapy.Ucwaningo oluningi luye lwaqinisekisa ukuthi amaseli omzimba angena ngesimila adlala indima ebalulekile ekuphenduleni i-cytotoxic chemotherapy [21, 22, 23].I-tumor immune microenvironment iyisici esibalulekile ekusindeni kweziguli zesimila [24, 25].I-Immunotherapy, ikakhulukazi ukwelashwa kwe-ICI, isetshenziswa kabanzi ekwelapheni izimila eziqinile [26].Izakhi zofuzo ezihlobene namasosha omzimba zisetshenziswa kabanzi ukuze kwakhiwe amamodeli engcuphe yokubikezela.Ngokwesibonelo, u-Su et al.Imodeli yengozi ehlobene nokuzivikela komzimba isekelwe kuzakhi zofuzo ze-protein-coding ukubikezela ukubikezelwa kweziguli zomdlavuza we-ovarian [27].Izakhi zofuzo ezingakhohlisi njenge-lncRNA nazo zifanelekile ekwakheni amamodeli engcuphe yokubikezela [28, 29, 30].U-Luo et al uhlole ama-lncRNA amane ahlobene nomzimba futhi wakha imodeli yokubikezela ingozi yomdlavuza womlomo wesibeletho [31].Khan et al.Ingqikithi yemibhalo ebhaliwe ye-32 evezwe ngokuhlukile ikhonjwe, futhi ngokusekelwe kulokhu, imodeli yokubikezela enemibhalo ebalulekile ye-5 yasungulwa, eyahlongozwa njengethuluzi elinconywe kakhulu lokubikezela ukwenqatshwa okunamandla okuqinisekisiwe kwe-biopsy ngemva kokufakelwa kwezinso [32].
Iningi lalawa mamodeli lisuselwe kumazinga wokuvezwa kwezakhi zofuzo, okungaba ama-protein-codeding noma ama-non-coding.Kodwa-ke, isakhi sofuzo esifanayo singaba namanani ahlukene wokukhuluma kuma-genome ahlukene, amafomethi wedatha kanye neziguli ezihlukene, okuholela ekulinganisweni okungazinzile kumamodeli aqagelayo.Kulolu cwaningo, sakhe imodeli ephusile enamapheya amabili e-lncRNAs, engaxhomekile kumanani wokusho okuyiwonawona.
Kulolu cwaningo, sihlonze i-irlncRNA okokuqala ngqa ngokuhlaziywa kokuhlobana nezakhi zofuzo ezihlobene nokuzivikela komzimba.Sihlole ama-DEirlncRNA angu-223 ngokuhlanganisa nama-lncRNA avezwe ngokuhlukile.Okwesibili, sakhe i-matrix engu-0-noma-1 ngokusekelwe endleleni yokumatanisa ye-DEirlncRNA eshicilelwe [31].Sibe sesihlaziya univariate kanye ne-lasso regression ukuze sihlonze amapheya e-DEirlncRNA abikezelayo futhi sakhe imodeli yengozi ebikezelayo.Siphinde sahlaziya ukuhlangana phakathi kwezikolo ezinobungozi nezici zomtholampilo ezigulini ezine-PAAD.Sithole ukuthi imodeli yethu yengozi yokubikezela, njengesici esizimele sokubikezela ezigulini ze-PAAD, ingakwazi ukuhlukanisa ngempumelelo iziguli ezisezingeni eliphezulu ezigulini ezisezingeni eliphansi kanye neziguli ezisezingeni eliphezulu ezigulini ezisezingeni eliphansi.Ngaphezu kwalokho, amanani e-AUC ejika le-ROC lemodeli yengozi yokubikezela ayengu-0.905 esibikezelo sonyaka ongu-1, angu-0.942 esibikezelo seminyaka emi-2, kanye no-0.966 esibikezelo seminyaka emi-3.
Abacwaningi babike ukuthi iziguli ezine-CD8+ T cell infiltration ephakeme zazizwela kakhulu ekwelashweni kwe-ICI [33].Ukwanda kokuqukethwe kwamaseli e-cytotoxic, amaseli e-CD56 NK, amaseli e-NK kanye namaseli e-CD8+ T ku-tumor immune microenvironment kungase kube esinye sezizathu zomphumela wokucindezela isimila [34].Ucwaningo lwangaphambilini lubonise ukuthi amazinga aphezulu e-CD4(+) T ne-CD8(+) T ahlotshaniswa kakhulu nokuphila isikhathi eside [35].Ukungena kahle kwamaseli e-CD8 T, umthwalo we-neoantigen ophansi, kanye ne-immune immunosuppressive microenvironment kuholela ekusweleni impendulo ekwelashweni kwe-ICI [36].Sithole ukuthi amaphuzu engcuphe ayehlotshaniswa kabi namaseli e-CD8+ T kanye namaseli e-NK, okubonisa ukuthi iziguli ezinezikolo ezisengozini enkulu zingase zingakufanelekeli ukwelashwa kwe-ICI futhi zibe nokubikezelwa okubi kakhulu.
I-CD161 iwuphawu lwamaseli abulalayo wemvelo (NK).I-CD8+CD161+ CAR-transduced cell cell mediate in vivo antitumor efficacy in HER2+ pancreatic ductal adenocarcinoma xenograft models [37].Ama-immune checkpoint inhibitors aqondisa i-cytotoxic T lymphocyte ehambisana namaprotheni 4 (CTLA-4) kanye nephrotheni yokufa kweseli ehleliwe 1 (PD-1)/i-programmed cell death ligand 1 (PD-L1) izindlela futhi inamandla amakhulu ezindaweni eziningi.Ukuvezwa kwe-CTLA-4 ne-CD161 (KLRB1) kuphansi emaqenjini asengozini enkulu, okubonisa futhi ukuthi iziguli ezinezikolo ezisengozini enkulu zingase zingafaneleki ukuthola ukwelashwa kwe-ICI.[38]
Ukuze sithole izinketho zokwelapha ezifanele iziguli ezisengozini enkulu, sihlaziye imithi ehlukahlukene elwa nomdlavuza futhi sathola ukuthi i-paclitaxel, i-sorafenib, ne-erlotinib, esetshenziswa kakhulu ezigulini ezine-PAAD, ingase ifanelekele iziguli ezisengozini enkulu nge-PAAD.[33].U-Zhang et al uthole ukuthi ukuguqulwa kwanoma iyiphi indlela yokusabela komonakalo we-DNA (DDR) kungaholela ekuqaguleni okubi kweziguli zomdlavuza we-prostate [39].Ukuhlolwa kwe-Pancreatic Cancer Olaparib Ongoing (POLO) kubonise ukuthi ukwelashwa kwesondlo nge-olaparib ukusinda isikhathi eside ngaphandle kokuqhubekela phambili uma kuqhathaniswa ne-placebo ngemva komugqa wokuqala we-chemotherapy-based chemotherapy ezigulini ezine-pancreatic ductal adenocarcinoma kanye nokuguqulwa kwe-germline BRCA1/2 [40].Lokhu kunikeza ithemba elibalulekile lokuthi imiphumela yokwelashwa izothuthuka kakhulu kuleli qembu elincane leziguli.Kulolu cwaningo, inani le-IC50 le-AZD.2281 (olaparib) laliphezulu eqenjini elinobungozi obukhulu, okubonisa ukuthi iziguli ze-PAAD eqenjini eliyingozi kakhulu zingase zimelane nokwelashwa nge-AZD.2281.
Amamodeli okubikezela kulolu cwaningo akhiqiza imiphumela emihle yokubikezela, kodwa asekelwe kwizibikezelo zokuhlaziya.Indlela yokuqinisekisa le miphumela ngedatha yomtholampilo kuwumbuzo obalulekile.I-Endoscopic finele aspiration ultrasonography (EUS-FNA) isiphenduke indlela ebaluleke kakhulu yokuxilonga izilonda eziqinile kanye ne-extrapancreatic pancreatic ngokuzwela okungama-85% kanye nokucaciswa okungu-98% [41].Ukuvela kwezinaliti ze-EUS fine-needle biopsy (EUS-FNB) kusekelwe kakhulukazi ezinhlelweni ezicatshangwayo ngaphezu kwe-FNA, njengokunemba okuphezulu kokuxilonga, ukuthola amasampula agcina ukwakheka kwe-histological, kanjalo kukhiqizwe izicubu zomzimba ezibalulekile ekuxilongeni okuthile .amabala akhethekile [42].Ukubuyekezwa okuhlelekile kwezincwadi kuqinisekisile ukuthi izinaliti ze-FNB (ikakhulukazi i-22G) zibonisa ukusebenza kahle okuphezulu kakhulu ekuvuneni izicubu ezivela ku-pancreatic mass [43].Ngokomtholampilo, inani elincane kuphela leziguli ezifanele ukuhlinzwa okukhulu, futhi iziguli eziningi zinezimila ezingasebenzi ngesikhathi sokuxilongwa kokuqala.Emisebenzini yomtholampilo, ingxenye encane kuphela yeziguli ezifanele ukuhlinzwa okukhulu ngoba iziguli eziningi zinezimila ezingasebenzi ngesikhathi sokuxilongwa kokuqala.Ngemuva kokuqinisekiswa kwe-pathological yi-EUS-FNB nezinye izindlela, ukwelashwa okujwayelekile okungahlinzeki okufana nokwelashwa ngamakhemikhali kuvamise ukukhethwa.Uhlelo lwethu lwakamuva locwaningo ukuhlola imodeli yokubikezela yalolu cwaningo kumaqoqo okuhlinza nabangahlinzeki ngokuhlaziya okubuyela emuva.
Sekukonke, ucwaningo lwethu lusungule imodeli entsha yengozi yokubikezela esekelwe ku-irlncRNA ebhanqiwe, ebonise inani elithembisayo lokubikezela ezigulini ezinomdlavuza we-pancreatic.Imodeli yethu yokubikezela ingozi ingase isize ukuhlukanisa iziguli ezine-PAAD ezifanele ukwelashwa.
Amasethi edatha asetshenzisiwe futhi ahlaziywa ocwaningweni lwamanje ayatholakala kumbhali ohambelanayo ngesicelo esifanele.
U-Sui Wen, u-Gong X, u-Zhuang Y. Indima yokulamula yokuzenzela amandla ekulawuleni imizwa yemizwa engemihle phakathi nobhadane lwe-COVID-19: ucwaningo oluhlukene.I-Int J Ment Health Nurs [isihloko sejenali].2021 06/01/2021;30(3):759–71.
Sui Wen, Gong X, Qiao X, Zhang L, Cheng J, Dong J, et al.Imibono yamalungu omndeni mayelana nokuthathwa kwezinqumo kwezinye izindawo ezikhungweni zabagula kakhulu: ukubuyekezwa okuhlelekile.I-INT J NURS STUD [isihloko sikamagazini;ukubuyekeza].2023 01/01/2023;137:104391.
Vincent A, Herman J, Schulich R, Hruban RH, Goggins M. Umdlavuza wePancreatic.I-Lancet.[Isihloko sejenali;ukwesekwa kocwaningo, i-NIH, i-extramural;ukwesekwa kocwaningo, uhulumeni ongaphandle kwe-US;ukubuyekeza].2011 08/13/2011;378(9791):607–20.
Ilic M, Ilic I. Epidemiology of pancreatic cancer.I-World Journal of Gastroenterology.[Isihloko sejenali, isibuyekezo].2016 11/28/2016;22(44):9694–705.
U-Liu X, u-Chen B, u-Chen J, u-Sun S. I-nomogram entsha ehlobene ne-tp53 yokubikezela ukusinda okuphelele kweziguli ezinomdlavuza we-pancreatic.I-BMC Cancer [isihloko sephephabhuku].2021 31-03-2021;21(1):335.
U-Xian X, u-Zhu X, u-Chen Y, u-Huang B, u-Xiang W. Umphumela wokwelashwa okugxile kwisixazululo ekukhathaleni okuhlobene nomdlavuza ezigulini ezinomdlavuza we-colorectal ezithola ukwelashwa ngamakhemikhali: isilingo esilawulwa ngokungahleliwe.Umhlengikazi womdlavuza.[Isihloko sejenali;ukuhlola okulawulwa ngokungahleliwe;ucwaningo lusekelwa uhulumeni ongaphandle kwe-United States].2022 05/01/2022;45(3):E663–73.
U-Zhang Cheng, u-Zheng Wen, uLu Y, u-Shan L, u-Xu Dong, u-Pan Y, et al.Amazinga we-Postoperative carcinoembryonic antigen (CEA) abikezela umphumela ngemuva kokukhishwa komdlavuza we-colorectal ezigulini ezinamazinga ajwayelekile e-CEA angaphambi kokuhlinzwa.Isikhungo Sokucwaninga Ngomdlavuza Wokuhumusha.[Isihloko sejenali].2020 01.01.2020;9(1):111–8.
Hong Wen, Liang Li, Gu Yu, Qi Zi, Qiu Hua, Yang X, et al.Ama-lncRNA ahlobene namasosha omzimba akhiqiza amasiginesha amanoveli futhi abikezele isimo somzimba sokuzivikela se-hepatocellular carcinoma yomuntu.I-Mol Ther Nucleic acids [Isihloko sejenali].2020 2020-12-04;22:937 - 47.
Toffey RJ, Zhu Y., Schulich RD Immunotherapy yomdlavuza we-pancreatic: izithiyo kanye nokuphumelela.U-Ann Udokotela Ohlinza Amathumbu [I-Journal Article;ukubuyekeza].2018 07/01/2018;2(4):274–81.
Hull R, Mbita Z, Dlamini Z. Long non-coding RNAs (LncRNAs), viral tumor genomics and aberrant splicing events: therapeutic implications.AM J CANCER RES [isihloko sejenali;ukubuyekeza].2021 01/20/2021;11(3):866–83.
Wang J, Chen P, Zhang Y, Ding J, Yang Y, Li H. 11-Ukuhlonza amasignesha e-lncRNA ahlotshaniswa nokubikezelwa komdlavuza we-endometrial.Izimpumelelo zesayensi [isihloko somagazini].2021 2021-01-01;104(1):311977089.
Jiang S, Ren H, Liu S, Lu Z, Xu A, Qin S, et al.Ukuhlaziywa okuphelele kwezakhi zofuzo ze-RNA ezibopha amaprotheni kanye nabaqokelwe izidakamizwa ku-papillary cell renal cell carcinoma.i-pregen.[Isihloko sejenali].2021 01/20/2021;12:627508.
U-Li X, u-Chen J, u-Yu Q, u-Huang X, u-Liu Z, u-Wang X, et al.Izici ze-RNA ehlobene ne-autophagy ende engekho ikhodi zibikezela ukubikezelwa komdlavuza webele.i-pregen.[Isihloko sejenali].2021 01/20/2021;12:569318.
U-Zhou M, u-Zhang Z, u-Zhao X, u-Bao S, u-Cheng L, u-Sun J. Isiginesha ye-lncRNA ehlobene nokuzivikela komzimba ithuthukisa ukubikezela ku-glioblastoma multiforme.I-MOL Neurobiology.[Isihloko sejenali].2018 01.05.2018;55(5):3684–97.
Wu B, Wang Q, Fei J, Bao Y, Wang X, Song Z, et al.Isiginesha yenoveli ye-tri-lncRNA ibikezela ukusinda kweziguli ezinomdlavuza we-pancreatic.ABAMELELI BE-ONKOL.[Isihloko sejenali].2018 12/01/2018;40(6):3427–37.
U-Luo C, u-Lin K, u-Hu C, u-Zhu X, u-Zhu J, u-Zhu Z. I-LINC01094 ikhuthaza ukuqhubeka komdlavuza we-pancreatic ngokulawula ukubonakaliswa kwe-LIN28B kanye nendlela ye-PI3K/AKT ngokusebenzisa i-sponged miR-577.I-Mol Therapeutics - Nucleic acids.2021;26:523–35.
Lin J, Zhai X, Zou S, Xu Z, Zhang J, Jiang L, et al.Impendulo enhle phakathi kwe-lncRNA FLVCR1-AS1 ne-KLF10 ingase ivimbele ukuqhubeka komdlavuza we-pancreatic ngokusebenzisa indlela ye-PTEN/AKT.J EXP Clin Cancer Res.2021;40(1).
Zhou X, Liu X, Zeng X, Wu D, Liu L. Ukuhlonzwa kwezakhi zofuzo eziyishumi nantathu ezibikezela ukusinda okuphelele ku-hepatocellular carcinoma.I-Biosci Rep [isihloko sephephabhuku].2021 04/09/2021.
Isikhathi sokuthumela: Sep-22-2023