Kankere ea Pancreatic ke e 'ngoe ea lihlahala tse bolaeang ka ho fetesisa lefatšeng tse nang le prognosis e mpe.Ka hona, ho hlokahala mohlala o nepahetseng oa ho bolela esale pele ho khetholla bakuli ba kotsing e kholo ea mofets'e oa pancreatic ho hlophisa kalafo le ho ntlafatsa boits'oaro ba bakuli bana.
Re fumane lintlha tsa The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq ho tsoa polokelong ea UCSC Xena, e bonts'itseng li-lncRNAs tse amanang le 'mele (irlncRNAs) ka tlhahlobo ea khokahano, mme ra tseba phapang lipakeng tsa TCGA le li-tissue tse tloaelehileng tsa pancreatic adenocarcinoma.DEirlncRNA) ho tloha TCGA le genotype tissue expression (GTEx) ea lisele tsa pancreatic.Ho ile ha etsoa litlhahlobo tse ling tse sa fetoheng le tsa lasso ho theha mehlala ea lipontšo tsa khale.Ka mor'a moo, re ile ra bala sebaka se ka tlas'a lekhalo 'me ra etsa qeto ea boleng bo nepahetseng ba ho khaola bakeng sa ho khetholla bakuli ba nang le kotsi e phahameng le e tlaase ea pancreatic adenocarcinoma.Ho bapisa litšoaneleho tsa kliniki, ho kenella ha lisele tsa 'mele tsa ho itšireletsa mafung, immunosuppressive microenvironment, le chemotherapy resistance ho bakuli ba nang le kankere ea pancreatic e kotsi haholo le e tlaase.
Re khethile lipara tse 20 tsa DEirlncRNA mme ra arola bakuli ho ea ka boleng bo nepahetseng ba cutoff.Re bonts'itse hore mohlala oa rona oa ho saena o na le ts'ebetso e kholo ho bolela esale pele hore na bakuli ba nang le PAAD ba tla joang.AUC ea curve ea ROC ke 0.905 bakeng sa ponelopele ea selemo se le seng, 0.942 bakeng sa ponelopele ea lilemo tse 2, le 0.966 bakeng sa ponelopele ea lilemo tse 3.Bakuli ba kotsing e kholo ba ne ba e-na le litekanyetso tse fokolang tsa ho phela le litšobotsi tse mpe tsa kliniki.Re boetse re bonts'itse hore bakuli ba kotsing e kholo ba na le immunosuppressed mme ba ka ba le ho hanyetsa immunotherapy.Tlhahlobo ea lithethefatsi tse thibelang kankere tse kang paclitaxel, sorafenib, le erlotinib tse thehiloeng ho lisebelisoa tsa ho bolela esale pele tsa k'homphieutha e ka ba tse loketseng bakuli ba kotsing e kholo ea PAAD.
Ka kakaretso, boithuto ba rona bo thehile mofuta o mocha oa kotsi oa kotsi o ipapisitseng le irlncRNA, e bonts'itseng boleng bo ts'episang ho bakuli ba nang le mofetše oa pancreatic.Mohlala oa rona oa kotsi o ka re thusang ho khetholla bakuli ba PAAD ba loketseng kalafo ea bongaka.
Kankere ea Pancreatic ke hlahala e kotsi e nang le sekhahla se tlase sa ho phela lilemo tse hlano le maemo a holimo.Nakong ea ho hlahlojoa, bakuli ba bangata ba se ba ntse ba le maemong a tsoetseng pele.Boemong ba seoa sa COVID-19, lingaka le baoki ba tlas'a khatello e kholo ha ba phekola bakuli ba mofetše oa pancreatic, mme malapa a bakuli le 'ona a tobana le likhatello tse ngata ha a etsa liqeto tsa kalafo [1, 2].Leha tsoelo-pele e kholo e entsoe kalafong ea DOADs, joalo ka kalafo ea neoadjuvant, ho buoa, kalafo ea radiation, chemotherapy, kalafo e lebisitsoeng ea molek'hule, le immune checkpoint inhibitors (ICIs), ke bakuli ba 9% feela ba pholohang lilemo tse hlano kamora ho hlahlojoa [3. ].], 4].Hobane matšoao a pele a pancreatic adenocarcinoma ke atypical, bakuli hangata ba fumanoa ba e-na le metastase nakong e tsoetseng pele.Ka hona, bakeng sa mokuli ea fuoeng, phekolo e felletseng ea motho ka mong e tlameha ho lekanya melemo le likotsi tsa likhetho tsohle tsa kalafo, eseng feela ho lelefatsa ho phela, empa hape le ho ntlafatsa boleng ba bophelo [6].Ka hona, mohlala o sebetsang oa ho bolela esale pele oa hlokahala ho lekola boemo ba mokuli ka nepo [7].Kahoo, phekolo e nepahetseng e ka khethoa ho leka-lekanya ho phela le boleng ba bophelo ba bakuli ba nang le PAAD.
Boemo bo bobe ba PAAD bo bakoa haholo ke ho hanyetsa lithethefatsi tsa chemotherapy.Lilemong tsa morao tjena, li-immune checkpoint inhibitors li 'nile tsa sebelisoa haholo ho phekola lihlahala tse tiileng [8].Leha ho le joalo, tšebeliso ea li-ICI ho mofetše oa pancreatic ha e atlehe ka seoelo [9].Ka hona, ke habohlokoa ho khetholla bakuli ba ka ruang molemo ho phekolo ea ICI.
RNA e telele e sa khouteng (lncRNA) ke mofuta oa RNA e sa khouteng e nang le lingoliloeng>200 nucleotides.Li-LncRNA li atile 'me li etsa hoo e ka bang 80% ea transcriptome ea motho [10].Mosebetsi o mongata o bonts'itse hore mefuta ea lncRNA e thehiloeng ho prognostic e ka bolela esale pele ka nepo boemo ba mokuli [11, 12].Ka mohlala, li-lncRNA tse 18 tse amanang le autophagy li ile tsa khetholloa ho hlahisa li-signatures tsa kankere ea matsoele [13].Li-lncRNA tse ling tse tšeletseng tse amanang le 'mele li sebelisitsoe ho theha likarolo tsa prognostic tsa glioma [14].
Ka mofets'e oa pancreatic, liphuputso tse ling li thehile li-signature tse thehiloeng ho lncRNA ho bolela esale pele hore na mokuli o tla tseba eng.Saeno ea 3-lncRNA e thehiloe ho pancreatic adenocarcinoma e nang le sebaka se tlas'a ROC curve (AUC) ea 0.742 feela le nako ea ho phela (OS) ea lilemo tse 3 [15].Ntle le moo, boleng ba polelo ea lncRNA bo fapana har'a liphatsa tsa lefutso tse fapaneng, lifomate tse fapaneng tsa data, le bakuli ba fapaneng, mme ts'ebetso ea mohlala o boletsoeng esale pele ha e tsitsa.Ka hona, re sebelisa mokhoa oa "model modeling algorithm", "pairing and iteration" ho hlahisa li-signature tsa lncRNA (irlncRNA) tse amanang le ho itšireletsa mafung ho theha mokhoa o nepahetseng le o tsitsitseng oa ho bolela esale pele [8].
Lintlha tse tloaelehileng tsa RNAseq (FPKM) le TCGA ea mofetše oa pancreatic TCGA le lintlha tsa genotype tissue expression (GTEx) li ile tsa fumanoa polokelong ea UCSC XENA (https://xenabrowser.net/datapages/).Lifaele tsa GTF li ile tsa fumanoa polokelong ea polokelo ea Ensembl ( http://asia.ensembl.org ) 'me tsa sebelisoa ho ntša li-profile tsa lncRNA ho tsoa ho RNAseq.Re khoasolla liphatsa tsa lefutso tse amanang le ho itšireletsa mafung ho tsoa polokelong ea ImmPort (http://www.immport.org) 'me ra tseba li-lncRNAs tse amanang le ho itšireletsa mafung (irlncRNAs) re sebelisa tlhahlobo ea khokahano (p <0.001, r > 0.4).Ho tsebahatsa li-irlncRNAs (DEirlncRNAs) tse hlahisoeng ka tsela e fapaneng (DEirlncRNAs) ka ho tšela irlncRNAs le lncRNA tse hlahisoang ka tsela e fapaneng tse fumanoeng polokelong ea GEPIA2 (http://gepia2.cancer-pku.cn/#index) ho sehlopha sa TCGA-PAAD (|logFC| > 1 le FDR <0.05).
Mokhoa ona o tlalehiloe pele [8].Ka ho khetheha, re haha X ho nka sebaka sa lncRNA A le lncRNA B. Ha boleng ba polelo ea lncRNA A bo phahametse boleng ba polelo ea lncRNA B, X e hlalosoa e le 1, ho seng joalo X e hlalosoa e le 0. Ka hona, re ka fumana matrix a 0 kapa - 1. Axis e emeng ea matrix e emela sampole ka 'ngoe,' me axis e otlolohileng e emela para e 'ngoe le e 'ngoe ea DEirlncRNA e nang le boleng ba 0 kapa 1.
Ho ile ha sebelisoa tlhahlobo e sa fetoheng ea ho theola maemo e lateloang ke Lasso regression ho lekola lipara tsa DEirlncRNA.Tlhahlobo ea regression ea lasso e sebelisitsoeng ka makhetlo a 10 ho tiisa sefapano ho pheta-pheta makhetlo a 1000 (p <0.05), ka 1000 e sa tloaelehang e susumetsang ka nako e le 'ngoe.Ha maqhubu a para e 'ngoe le e' ngoe ea DEirlncRNA a feta makhetlo a 100 ho li-cycle tse 1000, lipara tsa DEirlncRNA li ile tsa khethoa ho haha mohlala oa kotsi oa prognostic.Eaba re sebelisa curve ea AUC ho fumana boleng bo nepahetseng ba ho arola bakuli ba PAAD ka lihlopha tse kotsing e kholo le e tlase.Boleng ba AUC ba mohlala o mong le o mong le bona bo ile ba baloa le ho raloa joalo ka lekhalo.Haeba mothinya o fihla ntlheng e phahameng ka ho fetisisa e bonts'ang boleng bo phahameng ba AUC, ts'ebetso ea lipalo e ea emisa mme mohlala o nkuoa e le mokhethoa ea hloahloa.1-, 3- le 5-year curve mefuta ea ROC e hahiloe.Litlhahlobo tse sa fetoheng le tse ngata tse fapaneng li ile tsa sebelisoa ho hlahloba ts'ebetso e ikemetseng ea ho bolela esale pele ea mohlala oa kotsi.
Sebelisa lisebelisoa tse supileng ho ithuta litekanyetso tsa ho kenella ha lisele tsa 'mele, ho kenyelletsa XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, le CIBERSORT.Lintlha tsa ho kenella ha lisele tsa 'mele li kopitsoe ho tsoa bobolokelong ba TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Phapang ea litaba tsa lisele tse kenang 'meleng pakeng tsa lihlopha tse nang le kotsi e phahameng le e tlaase ea mohlala o hahiloeng li ile tsa hlahlojoa ho sebelisoa tlhahlobo ea boemo bo saenneng ea Wilcoxon, liphetho li bonts'oa ka graph graph.Ho ile ha etsoa tlhahlobo ea khokahano ea Spearman ho sekaseka kamano lipakeng tsa boleng ba lintlha tsa kotsi le lisele tse kenang 'meleng.Sephetho sa coefficient ea khokahano se bonts'oa joalo ka lollipop.Boemo ba bohlokoa bo ne bo behiloe ho p <0.05.Ts'ebetso e entsoe ho sebelisoa sephutheloana sa R ggplot2.Ho hlahloba kamano lipakeng tsa mohlala le maemo a polelo ea liphatsa tsa lefutso tse amanang le sekhahla sa ho kenella ha sele ea 'mele ea ho itšireletsa mafung, re entse sephutheloana sa ggstatsplot le pono ea morero oa violin.
Ho lekola mekhoa ea kalafo ea kliniki bakeng sa mofetše oa pancreatic, re balile IC50 ea litlhare tsa chemotherapy tse sebelisoang hangata sehlopheng sa TCGA-PAAD.Phapang pakeng tsa li-half inhibitory concentrations (IC50) pakeng tsa lihlopha tse nang le kotsi e phahameng le e tlaase li ile tsa bapisoa ho sebelisoa tlhahlobo ea boemo bo saenneng ba Wilcoxon, 'me liphello li bontšoa e le li-boxplots tse entsoeng ka ho sebelisa pRrophetic le ggplot2 ho R. Mekhoa eohle e lumellana le tataiso le mekhoa e nepahetseng.
Mosebetsi oa thuto ea rona o bontšoa ho Setšoantšo sa 1. Ho sebelisa tlhahlobo ea likamano pakeng tsa lncRNA le liphatsa tsa lefutso tse amanang le ho itšireletsa mafung, re khethile 724 irlncRNAs le p <0.01 le r> 0.4.Ka mor'a moo re ile ra hlahloba li-lncRNA tse hlalositsoeng ka tsela e fapaneng tsa GEPIA2 (Setšoantšo sa 2A).Kakaretso ea li-irlncRNA tse 223 li ile tsa hlahisoa ka tsela e fapaneng pakeng tsa pancreatic adenocarcinoma le lisele tse tloaelehileng tsa pancreatic (|logFC| > 1, FDR <0.05), tse bitsoang DEirlncRNAs.
Kaho ea mehlala ea kotsi e boletsoeng esale pele.(A) Morero oa seretse se chesang oa li-lncRNA tse hlalositsoeng ka mokhoa o fapaneng.(B) Kabo ea li-coefficients tsa lasso bakeng sa lipara tse 20 tsa DEirlncRNA.(C) Phapang e sa fellang ea monyetla oa ho ajoa ha coefficient ea LASSO.(D) Morero oa meru o bonts'a tlhahlobo e sa fetoheng ea ho khutlisetsoa morao ha lipara tse 20 tsa DEirlncRNA.
Ka mor'a moo re ile ra haha matrix ea 0 kapa 1 ka ho kopanya 223 DEirlncRNAs.Kakaretso ea lipara tsa DEirlncRNA tse 13,687 li khethiloe.Kamora tlhahlobo e sa fetoheng le ea lasso regression, lipara tse 20 tsa DEirlncRNA li ile tsa qetella li lekoa ho theha mohlala oa kotsi oa prognostic (Setšoantšo sa 2B-D).Ho itšetlehile ka liphello tsa Lasso le tlhahlobo e mengata ea ho khutlela morao, re ile ra bala palo ea kotsi bakeng sa mokuli e mong le e mong sehlopheng sa TCGA-PAAD (Letlapa la 1).Ho latela liphetho tsa tlhahlobo ea regression ea lasso, re balile palo ea kotsi bakeng sa mokuli e mong le e mong sehlopheng sa TCGA-PAAD.AUC ea curve ea ROC e ne e le 0.905 bakeng sa ponelopele ea mohlala oa kotsi ea selemo sa 1, 0.942 bakeng sa ponelopele ea lilemo tse 2, le 0.966 bakeng sa polelo ea lilemo tse 3 (setšoantšo sa 3A-B).Re ile ra beha boleng bo nepahetseng ba 3.105, ra arola bakuli ba sehlopha sa TCGA-PAAD ka lihlopha tse nang le kotsi e phahameng le e tlaase, 'me ra rera liphello tsa ho pholoha le ho fana ka lintlha tsa kotsi bakeng sa mokuli e mong le e mong (Setšoantšo sa 3C-E).Tlhahlobo ea Kaplan-Meier e bontšitse hore ho pholoha ha bakuli ba PAAD sehlopheng sa batho ba kotsing e kholo ho ne ho le tlase haholo ho feta ba bakuli ba sehlopha se tlaase (p <0.001) (Setšoantšo sa 3F).
Ho nepahala ha mehlala ea kotsi ea prognostic.(A) ROC ea mohlala oa kotsi ea prognostic.(B) 1-, 2-, le 3 ea lilemo tsa ROC ea prognostic mefuta ea kotsi.(C) ROC ea mohlala oa kotsi ea prognostic.E bonts'a sebaka se nepahetseng sa ho khaola.(DE) Kabo ea boemo ba ho pholoha (D) le lintlha tsa kotsi (E).(F) Tlhahlobo ea Kaplan-Meier ea bakuli ba PAAD ka lihlopha tse phahameng le tse tlaase.
Re ile ra tsoela pele ho hlahloba phapang pakeng tsa lintlha tsa kotsi ho latela litšobotsi tsa kliniki.Morero oa ho hlobolisa (setšoantšo sa 4A) se bontša kamano e akaretsang lipakeng tsa litšobotsi tsa bongaka le lintlha tsa kotsi.Ka ho khetheha, bakuli ba hōlileng ba ne ba e-na le lintlha tse phahameng tsa kotsi (Setšoantšo sa 4B).Ho phaella moo, bakuli ba nang le sethaleng sa II ba ne ba e-na le litekanyetso tse phahameng tsa kotsi ho feta bakuli ba nang le sethaleng sa I (Setšoantšo sa 4C).Mabapi le sehlopha sa tumor ho bakuli ba PAAD, bakuli ba sehlopha sa 3 ba ne ba e-na le lintlha tse phahameng tsa kotsi ho feta bakuli ba grade 1 le 2 (Figure 4D).Re ile ra tsoela pele ho etsa litlhahlobo tse sa fetoheng le tse ngata tse fapaneng mme ra bonts'a hore palo ea kotsi (p <0.001) le lilemo (p = 0.045) e ne e le lintlha tse ikemetseng tsa boits'oaro ho bakuli ba nang le PAAD (Setšoantšo sa 5A-B).Mokokotlo oa ROC o bontšitse hore palo ea kotsi e ne e phahametse litšobotsi tse ling tsa kliniki ho bolela esale pele 1-, 2-, le lilemo tsa 3 tsa ho phela ha bakuli ba nang le PAAD (Setšoantšo sa 5C-E).
Litšobotsi tsa kliniki tsa mehlala ea kotsi ea prognostic.Histogram (A) e bonts'a lilemo tsa (B), (C) sethala sa hlahala, (D) boemo ba tumor, lintlha tsa kotsi, le bong ba bakuli ba sehlopha sa TCGA-PAAD.**p <0.01
Tlhahlobo e ikemetseng ea ho bolela esale pele ea mehlala ea kotsi ea prognostic.(AB) Univariate (A) le multivariate (B) regression analysis of prognostic risk models and clinical characters.(CE) 1-, 2-, le 3-year ROC bakeng sa mehlala ea kotsi ea prognostic le litšobotsi tsa kliniki
Ka hona, re ile ra hlahloba kamano pakeng tsa nako le lintlha tsa kotsi.Re fumane hore palo ea kotsi ho bakuli ba PAAD e ne e amana ka tsela e fapaneng le lisele tsa CD8 + T le lisele tsa NK (Setšoantšo sa 6A), e leng se bontšang khatello ea 'mele ea ho itšireletsa mafung ho sehlopha se kotsi haholo.Hape re ile ra hlahloba phapang ea ho kenella ha lisele tsa 'mele tsa ho itšireletsa mafung pakeng tsa lihlopha tse nang le kotsi e phahameng le e tlaase' me ra fumana liphello tse tšoanang (Setšoantšo sa 7).Ho ne ho e-na le ho kenella ho fokolang ha lisele tsa CD8 + T le lisele tsa NK sehlopheng sa kotsi e kholo.Lilemong tsa morao tjena, immune checkpoint inhibitors (ICIs) e 'nile ea sebelisoa haholo ho phekola lihlahala tse tiileng.Leha ho le joalo, ts'ebeliso ea li-ICI ho mofetše oa pancreatic ha e e-so atlehe.Ka hona, re ile ra lekola polelo ea liphatsa tsa lefutso tsa tlhahlobo ea 'mele ka lihlopha tse kotsing e kholo le e tlase.Re fumane hore CTLA-4 le CD161 (KLRB1) li ne li feteletse haholo sehlopheng sa kotsi e tlaase (Setšoantšo sa 6B-G), se bontšang hore bakuli ba PAAD ba sehlopha sa kotsi e tlaase ba ka 'na ba e-ba le maikutlo a matle ho ICI.
Tlhahlobo ea khokahano ea mohlala oa kotsi ea prognostic le ho kenella ha lisele tsa 'mele.(A) Kamano lipakeng tsa mohlala oa kotsi oa prognostic le ho kenella ha lisele tsa 'mele.(BG) E bontša liphatsa tsa lefutso ka lihlopha tse nang le kotsi e phahameng le e tlaase.(HK) Litekanyetso tsa IC50 bakeng sa lithethefatsi tse itseng tsa anticancer ka lihlopha tse kotsing e kholo le e tlase.*p <0.05, **p <0.01, ns = ha e bohlokoa
Re ile ra tsoela pele ho lekola kamano lipakeng tsa lintlha tsa kotsi le li-agent tse tloaelehileng tsa chemotherapy sehlopheng sa TCGA-PAAD.Re batlile litlhare tsa anticancer tse sebelisoang hangata mofetšeng oa pancreatic mme ra sekaseka liphapang tsa boleng ba tsona ba IC50 lipakeng tsa lihlopha tse kotsing e kholo le e tlase.Liphello li bontšitse hore boleng ba IC50 ba AZD.2281 (olaparib) bo ne bo le holimo ho sehlopha se nang le kotsi e kholo, e bontšang hore bakuli ba PAAD ba sehlopha sa kotsi ba ka 'na ba hanyetsa phekolo ea AZD.2281 (Setšoantšo sa 6H).Ntle le moo, boleng ba IC50 ba paclitaxel, sorafenib le erlotinib bo ne bo le tlase sehlopheng se kotsing e kholo (Setšoantšo sa 6I-K).Re ile ra boela ra supa litlhare tse 34 tsa mofets'e tse nang le boleng bo phahameng ba IC50 sehlopheng se kotsing e kholo le lithethefatsi tse 34 tsa anticancer tse nang le boleng bo tlase ba IC50 sehlopheng se kotsing e kholo (Letlapa la 2).
Ho ke ke ha latoloa hore li-lncRNA, li-mRNA, le li-miRNA li teng ka bongata mme li bapala karolo ea bohlokoa kholong ea mofets'e.Ho na le bopaki bo bongata bo tšehetsang karolo ea bohlokoa ea mRNA kapa miRNA ho bolela esale pele ho pholoha ka kakaretso mefuteng e mengata ea mofetše.Ntle le pelaelo, mefuta e mengata ea kotsi ea prognostic e boetse e thehiloe ho li-lncRNAs.Ka mohlala, Luo et al.Liphuputso li bontšitse hore LINC01094 e phetha karolo ea bohlokoa ho ata ha PC le metastasis, 'me polelo e phahameng ea LINC01094 e bontša ho phela hampe ha bakuli ba kankere ea pancreatic [16].Thuto e hlahisitsoeng ke Lin et al.Liphuputso li bonts'itse hore ho fokotseha ha lncRNA FLVCR1-AS1 ho amahanngoa le ho fosahetse ho bakuli ba mofetše oa pancreatic [17].Leha ho le joalo, li-lncRNA tse amanang le boits'ireletso ha li buuoe hanyane ho latela ho bolela esale pele ho phela ha bakuli ba mofetše.Haufinyane tjena, mosebetsi o mongata o tsepamisitse maikutlo ho aheng mekhoa ea kotsi ea ho bolela esale pele ho pholoha ha bakuli ba mofetše mme ka hona ho fetola mekhoa ea kalafo [18, 19, 20].Ho na le tlhokomeliso e ntseng e hola ea karolo ea bohlokoa ea ho kenella ha 'mele oa ho itšireletsa mafung ho qaleng ha mofetše, tsoelo-pele, le karabelo ho liphekolo tse joalo ka chemotherapy.Liphuputso tse ngata li tiisitse hore lisele tsa 'mele tsa ho itšireletsa mafung tse kenang ka hlahala li phetha karolo ea bohlokoa karabelong ea cytotoxic chemotherapy [21,22,23].Tikoloho ea 'mele ea ho itšireletsa mafung ea tumor ke ntlha ea bohlokoa molemong oa ho phela ha bakuli ba hlahala [24, 25].Immunotherapy, haholo-holo phekolo ea ICI, e sebelisoa haholo ho phekola lihlahala tse tiileng [26].Liphatsa tsa lefutso tse amanang le 'mele oa ho itšireletsa mafung li sebelisoa haholo ho aha mefuta ea kotsi ea prognostic.Ka mohlala, Su et al.Mokhoa oa kotsi o amanang le 'mele oa ho itšireletsa mafung o itšetlehile ka liphatsa tsa lefutso tsa protheine ho bolela esale pele hore na bakuli ba mofetše oa mahe a bomme [27].Liphatsa tsa lefutso tse se nang likhoutu tse joalo ka li-lncRNA le tsona li loketse ho aha mefuta ea kotsi e boletsoeng esale pele [28, 29, 30].Luo et al o ile a leka li-lncRNA tse 'nè tse amanang le' mele oa ho itšireletsa mafung 'me a haha mohlala oa ho bolela esale pele bakeng sa kotsi ea mofetše oa popelo [31].Khan et al.Kakaretso ea litlaleho tse 32 tse hlalositsoeng ka mokhoa o fapaneng li ile tsa fumanoa, 'me ho itšetlehile ka sena, ho ile ha thehoa mohlala oa ho bolela esale pele o nang le litlaleho tsa bohlokoa tsa 5, tse ileng tsa hlahisoa e le sesebelisoa se khothalelitsoeng haholo bakeng sa ho bolela esale pele ho lahloa ho matla ho netefalitsoeng ka biopsy kamora ho fetisoa ha liphio [32].
Boholo ba mefuta ena e ipapisitse le maemo a polelo ea liphatsa tsa lefutso, ebang ke liphatsa tsa lefutso tsa protheine kapa tse sa khouteng.Leha ho le joalo, mofuta o tšoanang o ka ba le litekanyetso tse fapaneng tsa polelo ho liphatsa tsa lefutso tse fapaneng, lifomate tsa data le ho bakuli ba fapaneng, e lebisang ho likhakanyo tse sa tsitsang mefuteng e boletsoeng esale pele.Thutong ena, re thehile mohlala o utloahalang o nang le lipara tse peli tsa lncRNAs, ntle le litekanyetso tse hlakileng tsa polelo.
Thutong ena, re khethile irlncRNA khetlo la pele ka tlhahlobo ea khokahano le liphatsa tsa lefutso tse amanang le boits'ireletso.Re hlahlobile li-DEirlncRNA tse 223 ka ho kopanya ka li-lncRNA tse hlahisitsoeng ka mokhoa o fapaneng.Ea bobeli, re thehile matrix a 0-kapa-1 ho latela mokhoa o hatisitsoeng oa ho kopanya oa DEirlncRNA [31].Ka mor'a moo re ile ra etsa litlhahlobo tse sa fetoheng le tsa lasso ho hlwaya lipara tsa DEirlncRNA le ho theha mohlala oa kotsi o boletsoeng esale pele.Re ile ra boela ra hlahloba kamano pakeng tsa lintlha tsa kotsi le litšobotsi tsa kliniki ho bakuli ba nang le PAAD.Re fumane hore mohlala oa rona oa kotsi, e le ntho e ikemetseng ea prognostic ho bakuli ba PAAD, e ka atleha ho khetholla bakuli ba boemo bo phahameng ho tloha ho bakuli ba boemo bo tlaase le bakuli ba boemo bo phahameng ho tloha ho bakuli ba tlaase.Ntle le moo, boleng ba AUC ba ROC curve ea mohlala oa kotsi ea prognostic e ne e le 0.905 bakeng sa ponelopele ea selemo se le seng, 0.942 bakeng sa ponelopele ea lilemo tse 2, le 0.966 bakeng sa ponelopele ea lilemo tse 3.
Bafuputsi ba tlalehile hore bakuli ba nang le tšoaetso e phahameng ea CD8 + T cell ba ne ba amehile haholo ho phekolo ea ICI [33].Ho eketseha ha dikahare tsa cytotoxic lisele tse, CD56 NK lisele tse, NK lisele le CD8+ T lisele tse ka hlahala boitshireletso microenvironment ka 'na ba e mong oa mabaka a hore hlahala suppressive phello [34].Liphuputso tse fetileng li bontšitse hore litekanyetso tse phahameng tsa CD4 (+) T le CD8 (+) T li ne li amahanngoa haholo le ho phela nako e telele [35].Ho kenella ha lisele tsa CD8 T tse futsanehileng, moroalo o tlase oa neoantigen, le "tumor" e fokolang haholo ea "immunosuppressive" e lebisa ho se arabeleng kalafo ea ICI [36].Re fumane hore palo ea kotsi e ne e amana hampe le lisele tsa CD8 + T le lisele tsa NK, tse bontšang hore bakuli ba nang le menyetla e mengata ea kotsi ba ka 'na ba se ke ba tšoaneleha bakeng sa phekolo ea ICI 'me ba e-na le tšoaetso e mpe le ho feta.
CD161 ke letšoao la lisele tse bolaeang tsa tlhaho (NK).CD8 + CD161+ CAR-transduced T cell mediate e matlafalitsoe ka katleho ea vivo antitumor ho HER2 + pancreatic ductal adenocarcinoma xenograft models [37].Immune checkpoint inhibitors target cytotoxic T lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) litsela 'me li na le bokhoni bo boholo libakeng tse ngata.Tlhaloso ea CTLA-4 le CD161 (KLRB1) e tlaase lihlopheng tse nang le kotsi e kholo, e tsoelang pele e bontšang hore bakuli ba nang le likotsi tse ngata ba ka 'na ba se ke ba fumana phekolo ea ICI.[38]
E le ho fumana mekhoa ea phekolo e loketseng bakuli ba kotsing e kholo, re ile ra hlahloba lithethefatsi tse sa tšoaneng tsa anticancer mme ra fumana hore paclitaxel, sorafenib, le erlotinib, tse sebelisoang haholo ho bakuli ba nang le PAAD, e ka 'na ea e-ba tse loketseng bakuli ba kotsing e kholo ea PAAD.[33].Zhang et al o fumane hore liphetoho tseleng efe kapa efe ea DNA ea tšenyo ea DNA (DDR) li ka lebisa tlhokomelong e mpe ho bakuli ba mofetše oa prostate [39].Teko ea Pancreatic Cancer Olaparib Ongoing (POLO) e bontšitse hore kalafo ea tlhokomelo e nang le olaparib e tšoarellang nako e telele ea ho phela ntle le tsoelo-pele ha e bapisoa le placebo kamora chemotherapy e thehiloeng ho platinum ea pele ho bakuli ba nang le pancreatic ductal adenocarcinoma le germline BRCA1/2 liphetoho tsa BRCA1/2.Sena se fana ka tšepo e kholo ea hore liphello tsa phekolo li tla ntlafala haholo sehlopheng sena sa bakuli.Phuputsong ena, boleng ba IC50 ba AZD.2281 (olaparib) bo ne bo le holimo ho sehlopha se nang le kotsi e kholo, e bontšang hore bakuli ba PAAD ba sehlopha sa kotsi ba ka 'na ba hanyetsa phekolo ea AZD.2281.
Mehlala ea ho bolela esale pele thutong ena e hlahisa litholoana tse ntle tsa ho bolela esale pele, empa e ipapisitse le ponelopele ea tlhahlobo.Mokhoa oa ho netefatsa liphetho tsena ka data ea kliniki ke potso ea bohlokoa.Endoscopic fine needle aspiration ultrasonography (EUS-FNA) e se e le mokhoa oa bohlokoahali oa ho hlahloba liso tsa pancreatic tse tiileng le tsa extrapancreatic ka kutlo ea 85% le tse ikhethang tsa 98% [41].Ho fihla ha linale tsa EUS-needle biopsy (EUS-FNB) ho ipapisitse le melemo eo ho nahanoang hore e feta FNA, joalo ka ho nepahala ho phahameng hoa tlhahlobo, ho fumana lisampole tse bolokang sebopeho sa histological, ka hona ho hlahisa lisele tsa 'mele tse bohlokoa bakeng sa tlhahlobo e itseng.matheba a khethehileng [42].Tlhahlobo e hlophisitsoeng ea lingoliloeng e netefalitse hore linale tsa FNB (haholo-holo 22G) li bonts'a ts'ebetso e phahameng ka ho fetisisa ea ho kotula lisele tse tsoang matšoeleng a pancreatic [43].Ho ea ka meriana, ke bakuli ba fokolang feela ba tšoanelehang bakeng sa ho buuoa ka matla, 'me bakuli ba bangata ba na le lihlahala tse sa sebetseng nakong ea tlhahlobo ea pele.Ts'ebetsong ea bongaka, ke karolo e nyane feela ea bakuli ba loketseng ho buuoa ka matla hobane bakuli ba bangata ba na le lihlahala tse sa sebetseng nakong ea tlhahlobo ea pele.Kamora ho netefatsoa ke lefu la EUS-FNB le mekhoa e meng, hangata ho khethoa kalafo e tloaelehileng e sa buuoeng joalo ka chemotherapy.Lenaneo la rona la morao-rao la lipatlisiso ke ho leka mohlala oa prognostic oa phuputso ena ho lihlopha tsa batho ba buoang le ba sa buuoeng ka tlhahlobo ea morao-rao.
Ka kakaretso, boithuto ba rona bo thehile mofuta o mocha oa kotsi oa kotsi o ipapisitseng le irlncRNA, e bonts'itseng boleng bo ts'episang ho bakuli ba nang le mofetše oa pancreatic.Mohlala oa rona oa kotsi o ka re thusang ho khetholla bakuli ba PAAD ba loketseng kalafo ea bongaka.
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Nako ea poso: Sep-22-2023