Igisekuru cya Immune ifitanye isano na LncRNA ishingiye ku mukono kugirango tumenye abarwayi ba pancreatic Adenocarcinoma Indwara Yisumbuye kandi Ntoya |BMC Gastroenterology

Kanseri y'urwagashya ni kimwe mu bibyimba byica abantu ku isi hamwe no kutamenya neza.Niyo mpamvu, hakenewe uburyo nyabwo bwo guhanura kugira ngo hamenyekane abarwayi bafite ibyago byinshi byo kurwara kanseri yandura kugira ngo bavurwe neza kandi banonosore imenyekanisha ry’abo barwayi.
Twabonye Kanseri Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq amakuru yo mu bubiko bwa UCSC Xena, tumenya lncRNAs (irlncRNAs) zifitanye isano n’ubudahangarwa dukoresheje isesengura rifitanye isano, tunagaragaza itandukaniro riri hagati ya TCGA nuduce dusanzwe twa adenocarcinoma.DEirlncRNA) kuva TCGA hamwe na genotype yerekana imvugo (GTEx) ya tissue pancreatic tissue.Ubundi isesengura rya univariate na lasso ryakozwe kugirango hubakwe icyitegererezo cyerekana umukono.Twahise tubara agace kari munsi y'umurongo hanyuma tumenye agaciro keza ko kugabanya abarwayi bafite pancreatic adenocarcinoma ifite ibyago byinshi kandi bike.Kugereranya ibiranga ivuriro, kwinjiza ingirabuzimafatizo, micro-ibidukikije ikingira immunosuppressive, hamwe na chimiotherapie irwanya abarwayi bafite kanseri yandura cyane.
Twabonye 20 DEirlncRNA ebyiri hamwe nitsinda ryabarwayi dukurikije agaciro keza.Twerekanye ko icyitegererezo cyumukono wa prognostic gifite imikorere igaragara muguhishurira prognoza yabarwayi bafite PAAD.AUC y'umurongo wa ROC ni 0.905 kubiteganijwe umwaka 1, 0.942 kubiteganijwe mu myaka 2, na 0.966 kubiteganijwe mu myaka 3.Abarwayi bafite ibyago byinshi bari bafite ubuzima buke bwo kubaho kandi biranga ivuriro.Twerekanye kandi ko abarwayi bafite ibyago byinshi bafite ubudahangarwa kandi bashobora guteza imbere ubudahangarwa bw'umubiri.Isuzuma ry'imiti igabanya ubukana nka paclitaxel, sorafenib, na erlotinib ishingiye ku bikoresho byo kubara bishobora kuba byiza ku barwayi bafite ibyago byinshi bafite PAAD.
Muri rusange, ubushakashatsi bwacu bwashyizeho uburyo bushya bwo kumenya ingaruka zishingiye kuri irlncRNA zombi, zerekanaga agaciro keza ko gutangaza abarwayi barwaye kanseri yandura.Icyitegererezo cyibyago bishobora gufasha gutandukanya abarwayi bafite PAAD babereye kwivuza.
Kanseri y'urwagashya ni ikibyimba kibi gifite ubuzima buke bw'imyaka itanu yo kubaho no mu rwego rwo hejuru.Mugihe cyo kwisuzumisha, abarwayi benshi basanzwe bari mubyiciro byiterambere.Mu rwego rw'icyorezo cya COVID-19, abaganga n'abaforomo bafite igitutu kinini iyo bavura abarwayi ba kanseri yandura, kandi imiryango y'abarwayi nayo ihura n'ibibazo byinshi iyo bafata ibyemezo byo kuvura [1, 2].Nubwo hari intambwe nini imaze guterwa mu kuvura DOADs, nko kuvura neoadjuvant, kuvura indwara, kuvura imishwarara, imiti ya chimiotherapie, kuvura indwara ya molekuline, hamwe no gukumira indwara zanduza indwara (ICIs), abarwayi bagera kuri 9% gusa ni bo barokoka imyaka itanu nyuma yo kwisuzumisha [3 ].], 4].Kubera ko ibimenyetso byambere bya pancreatic adenocarcinoma bidasanzwe, abarwayi basuzumwa metastase mugihe cyateye imbere [5].Kubwibyo, kumurwayi runaka, ubuvuzi bwihariye bugomba gusuzuma ibyiza nibibi byubuvuzi bwose, atari ukuramba gusa, ahubwo no kuzamura imibereho [6].Niyo mpamvu, uburyo bwiza bwo guhanura burakenewe kugirango dusuzume neza uko umurwayi amenya [7].Rero, ubuvuzi bukwiye burashobora gutoranywa kugirango habeho kubaho nubuzima bwiza bwabarwayi bafite PAAD.
Kumenyekanisha nabi kwa PAAD biterwa ahanini no kurwanya imiti ya chimiotherapie.Mu myaka yashize, imiti igabanya ubukana yakoreshejwe cyane mu kuvura ibibyimba bikomeye [8].Ariko, gukoresha ICI muri kanseri yandura ni gake cyane [9].Niyo mpamvu, ni ngombwa kumenya abarwayi bashobora kungukirwa nubuvuzi bwa ICI.
RNA ndende idafite code (lncRNA) ni ubwoko bwa RNA idafite code hamwe na transcript> 200 nucleotide.LncRNAs irakwirakwiriye kandi igizwe na 80% by'inyandiko-mvugo y'umuntu [10].Umubiri munini wakazi werekanye ko lncRNA yerekana imiterere yerekana ibimenyetso bishobora guhanura neza abarwayi [11, 12].Kurugero, lncRNAs 18 zifitanye isano na autophagy zagaragaye kugirango zitange umukono uteganijwe muri kanseri yamabere [13].Ibindi bitandatu bifitanye isano n'ubudahangarwa lncRNAs byakoreshejwe kugirango hamenyekane ibimenyetso biranga glioma [14].
Muri kanseri yandura, ubushakashatsi bumwe na bumwe bwashyizeho umukono ushingiye kuri lncRNA yo guhanura abarwayi.Umukono wa 3-lncRNA washyizweho muri pancreatic adenocarcinoma ifite agace kari munsi yumurongo wa ROC (AUC) ya 0.742 gusa hamwe nubuzima rusange (OS) bwimyaka 3 [15].Mubyongeyeho, indangagaciro za lncRNA ziratandukanye muri genome zitandukanye, imiterere yamakuru atandukanye, nabarwayi batandukanye, kandi imikorere yuburyo bwo guhanura ntabwo ihagaze.Kubwibyo, dukoresha uburyo bushya bwo kwerekana algorithm, guhuza no gutondekanya, kugirango tubyare umukono ujyanye nubudahangarwa bwa lncRNA (irlncRNA) kugirango dukore icyitegererezo cyukuri kandi gihamye [8].
Amakuru asanzwe ya RNAseq (FPKM) hamwe na kanseri yandura kanseri ya TCGA hamwe na genotype yerekana imiterere (GTEx) yabikuye mububiko bwa UCSC XENA (https://xenabrowser.net/datapages/).Idosiye ya GTF yabonetse mububiko bwa Ensembl (http://asia.ensembl.org) kandi ikoreshwa mugukuramo imyirondoro ya lncRNA muri RNAseq.Twakuyeho genes zijyanye n'ubudahangarwa tuvuye muri base ya ImmPort (http://www.immport.org) hanyuma tumenya lncRNAs zijyanye n'ubudahangarwa (irlncRNAs) dukoresheje isesengura rifitanye isano (p <0.001, r> 0.4).Kumenyekanisha mu buryo butandukanye irlncRNAs (DEirlncRNAs) mu kwambuka irlncRNAs no kwerekana mu buryo butandukanye lncRNAs yakuwe mu bubiko bwa GEPIA2 (http://gepia2.cancer-pku.cn/#index) muri cohort ya TCGA-PAAD (| logFC |> 1 na FDR ) <0.05).
Ubu buryo bwatangajwe mbere [8].By'umwihariko, twubaka X kugirango dusimbuze lncRNA A hamwe na lncRNA B. Iyo imvugo yagaciro ya lncRNA A irenze agaciro kerekana imvugo ya lncRNA B, X isobanurwa nka 1, naho ubundi X isobanurwa nka 0. Kubwibyo, dushobora kubona matrike ya 0 cyangwa - 1. Uhagaritse umurongo wa matrix ugereranya buri cyitegererezo, naho umurongo utambitse ugereranya buri DEirlncRNA hamwe nagaciro ka 0 cyangwa 1.
Isesengura ryisubiramo rimwe rikurikirwa no gusubira inyuma kwa Lasso ryakoreshejwe mugusuzuma ibyamenyekanye DEirlncRNA byombi.Isesengura ryisubiramo rya lasso ryakoresheje inshuro 10 kwambukiranya inshuro inshuro 1000 (p <0.05), hamwe na 1000 zidasanzwe zidasanzwe kuri buri kwiruka.Iyo inshuro ya buri couple ya DEirlncRNA yarenze inshuro 100 mukuzenguruka 1000, ibice bibiri bya DEirlncRNA byatoranijwe kugirango byubake icyitegererezo cyerekana ingaruka.Twahise dukoresha umurongo wa AUC kugirango tubone agaciro keza ko kugabanya abarwayi ba PAAD mumatsinda menshi kandi afite ibyago bike.Agaciro AUC ya buri moderi nayo yabazwe kandi yateguwe nkumurongo.Niba umurongo ugeze kumurongo wo hejuru werekana agaciro ntarengwa AUC, inzira yo kubara irahagarara kandi icyitegererezo gifatwa nkumukandida mwiza.Moderi ya 1-, 3- na 5 yimyaka ya ROC yuhetamye yubatswe.Isesengura rya univariate na multivariate ryakoreshejwe mugusuzuma imikorere yigenga yo guteganya ibyitegererezo byerekana ingaruka.
Koresha ibikoresho birindwi kugirango wige ibipimo byinjira mu ngirabuzimafatizo, harimo XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, na CIBERSORT.Amakuru yinjira mu ngirabuzimafatizo yakuwe mu bubiko bwa TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Itandukaniro riri mubiri mu ngirabuzimafatizo zinjira mu mubiri hagati y’amatsinda menshi kandi afite ibyago bike by’icyitegererezo cyubatswe yasesenguwe hifashishijwe ikizamini cya Wilcoxon cyashyizweho umukono, ibisubizo byerekanwe ku gishushanyo mbonera.Isesengura rifitanye isano nicumu ryakozwe kugirango isesengure isano iri hagati y amanota yingaruka ziterwa ningirabuzimafatizo.Coefficient ijyanye nayo yerekanwe nka lollipop.Akamaro kashyizweho kuri p <0.05.Inzira yakozwe hakoreshejwe R pack ggplot2.Kugirango dusuzume isano iri hagati yicyitegererezo nurwego rwerekana imiterere ijyanye nigipimo cyumudugudu winjira, twakoze pake ya ggstatsplot hamwe na violon yerekana amashusho.
Kugirango dusuzume uburyo bwo kuvura kwa kanseri yandura, twabaze IC50 yimiti ikoreshwa cyane muri chimiotherapie muri TCGA-PAAD.Itandukaniro muri kimwe cya kabiri cyokwirinda (IC50) hagati yitsinda ryinshi kandi rifite ibyago bike wagereranijwe ukoresheje ikizamini cyashyizweho umukono na Wilcoxon, kandi ibisubizo byerekanwe nkibisanduku byatanzwe hakoreshejwe pRRophetic na ggplot2 muri R. Uburyo bwose bukurikiza amabwiriza ngenderwaho.
Urujya n'uruza rw'inyigisho zacu rwerekanwe ku gishushanyo cya 1. Dukoresheje isesengura rifitanye isano na lncRNAs na gen zijyanye n'ubudahangarwa, twahisemo 724 irlncRNAs hamwe na p <0.01 na r> 0.4.Ubukurikira twasesenguye lncRNAs zitandukanye zitandukanye za GEPIA2 (Ishusho 2A).223 irlncRNAs zagaragajwe mu buryo butandukanye hagati ya pancreatic adenocarcinoma na tissue pancreatic tissue (| logFC |> 1, FDR <0.05), yitwa DEirlncRNAs.
Kubaka ibyitegererezo byerekana ingaruka.(A) Umugambi wibirunga wa lncRNAs zitandukanye.(B) Ikwirakwizwa rya coefficient ya lasso kuri 20 DEirlncRNA ebyiri.(C) Ibice bimwe bitandukana byo gukwirakwiza coefficient ya LASSO.(D) Ikibanza cyamashyamba cyerekana isesengura ryisubiramo rimwe rya 20 DEirlncRNA ebyiri.
Ubukurikira twubatse matrike 0 cyangwa 1 duhuza 223 DEirlncRNAs.Bose hamwe 13,687 DEirlncRNA babiri bamenyekanye.Nyuma yisesengura rya univariate na lasso, 20 DEirlncRNA ebyiri zarangije kugeragezwa kugirango hubakwe icyitegererezo cyerekana ingaruka (Ishusho 2B-D).Dushingiye ku bisubizo bya Lasso hamwe nisesengura ryinshi ryisubiramo, twabaze amanota yingaruka kuri buri murwayi muri cohort ya TCGA-PAAD (Imbonerahamwe 1).Dushingiye ku bisubizo by'isesengura rya lasso, twabaze amanota y'ingaruka kuri buri murwayi muri TCGA-PAAD.AUC yumurongo wa ROC yari 0.905 kubiteganijwe kumyaka 1 yerekana ibyago, 0.942 kubihanura byimyaka 2, na 0.966 kubihanura byimyaka 3 (Ishusho 3A-B).Twashyizeho uburyo bwiza bwo kugabanya agaciro ka 3.105, dushyira abarwayi ba TCGA-PAAD mu itsinda ry’abantu benshi kandi bafite ibyago bike, kandi duteganya ibyavuye mu mibereho no kugabana amanota kuri buri murwayi (Ishusho 3C-E).Isesengura rya Kaplan-Meier ryerekanye ko kubaho kw'abarwayi ba PAAD mu itsinda ry’ibyago byinshi byari hasi cyane ugereranije n’abarwayi bo mu itsinda rifite ibyago bike (p <0.001) (Ishusho 3F).
Agaciro k'icyitegererezo cyerekana ingaruka.(A) ROC yicyitegererezo cyerekana ingaruka.(B) 1-, 2-, na 3-ROC yerekana ibyago byerekana ingaruka.(C) ROC yicyitegererezo cyerekana ingaruka.Erekana ingingo nziza yo guca.(DE) Ikwirakwizwa ryimiterere yo kubaho (D) n amanota yingaruka (E).(F) Kaplan-Meier isesengura ryabarwayi ba PAAD mumatsinda menshi kandi afite ibyago bike.
Twongeye gusuzuma itandukaniro ryamanota yingaruka ziterwa nubuvuzi.Igishushanyo mbonera (Igicapo 4A) cerekana isano rusange hagati yimiterere yubuvuzi n amanota yingaruka.By'umwihariko, abarwayi bakuze bagize amanota menshi (Ishusho 4B).Byongeye kandi, abarwayi bafite icyiciro cya II bafite amanota menshi kurusha abarwayi bafite icyiciro cya I (Ishusho 4C).Ku bijyanye n'ikibyimba ku barwayi ba PAAD, abarwayi bo mu cyiciro cya 3 bafite amanota menshi kurusha abarwayi bo mu cyiciro cya 1 n'icya 2 (Ishusho 4D).Twongeye gukora isesengura rinyuranye kandi rinyuranye kandi twerekana ko amanota yingaruka (p <0.001) n'imyaka (p = 0.045) aribintu byigenga byamenyekanye kubarwayi barwaye PAAD (Igicapo 5A-B).Umurongo wa ROC werekanye ko amanota y’ibyago yarutaga ibindi biranga amavuriro mu guhanura ubuzima bw’abarwayi barwaye PAAD 1-, 2-, na 3 (Ishusho 5C-E).
Ibiranga ivuriro ryerekana ibyago byerekana ingaruka.Histogramu (A) yerekana (B) imyaka, (C) icyiciro cyibibyimba, (D) igipimo cyibibyimba, amanota yingaruka, nuburinganire bwabarwayi bo muri TCGA-PAAD.** p <0.01
Isesengura ryigenga ryo gusesengura ibyitegererezo byerekana ingaruka..:
Kubwibyo, twasuzumye isano iri hagati yigihe n amanota yingaruka.Twabonye ko amanota y’ibyago ku barwayi ba PAAD yari afitanye isano rya bugufi na CD8 + T na selile NK (Igishusho 6A), byerekana imikorere y’ubudahangarwa mu itsinda rifite ibyago byinshi.Twasuzumye kandi itandukaniro ryinjira mu ngirabuzimafatizo hagati y’amatsinda menshi kandi afite ibyago bike kandi dusanga ibisubizo bimwe (Ishusho 7).Habayeho gucengeza gake kwa CD8 + T na selile NK mumatsinda afite ibyago byinshi.Mu myaka yashize, imiti igabanya ubukana (ICIs) yakoreshejwe cyane mu kuvura ibibyimba bikomeye.Ariko, gukoresha ICI muri kanseri yandura ntago byagenze neza.Kubwibyo, twasuzumye imvugo ya gen igenzura immunite mumatsinda menshi kandi afite ibyago bike.Twasanze CTLA-4 na CD161 (KLRB1) byarakabije cyane mu itsinda rifite ibyago bike (Ishusho 6B-G), byerekana ko abarwayi ba PAAD bari mu itsinda rifite ibyago bike bashobora kumva ICI.
Isesengura rifitanye isano na prognostic risque model hamwe na immun selile yinjira.(A) Isano riri hagati yingero ziterwa ningaruka ziterwa no kwanduza ingirabuzimafatizo.(BG) Yerekana imvugo ya gene mumatsinda menshi kandi make.(HK) IC50 indangagaciro kumiti yihariye ya anticancer mumatsinda menshi kandi make.* p <0.05, ** p <0.01, ns = ntabwo ari ngombwa
Twongeye gusuzuma isano iri hagati yamanota yingaruka hamwe na chimiotherapie isanzwe muri TCGA-PAAD cohort.Twashakishije imiti ikoreshwa cyane muri kanseri yandura kandi tunasesengura itandukaniro riri hagati yagaciro ka IC50 hagati yitsinda ryinshi kandi rifite ibyago bike.Ibisubizo byagaragaje ko agaciro ka IC50 ka AZD.2281 (olaparib) kari hejuru mu itsinda ry’ibyago byinshi, byerekana ko abarwayi ba PAAD bo mu itsinda ry’ibyago byinshi bashobora kurwanya AZD.2281 (Ishusho 6H).Mubyongeyeho, indangagaciro za IC50 za paclitaxel, sorafenib, na erlotinib zari hasi mumatsinda afite ibyago byinshi (Ishusho 6I-K).Twongeye kumenya imiti 34 ya anticancer ifite agaciro gakomeye ka IC50 mu itsinda ry’ibyago byinshi hamwe n’imiti 34 ya anticancer ifite agaciro ka IC50 mu itsinda rifite ibyago byinshi (Imbonerahamwe 2).
Ntidushobora guhakana ko lncRNAs, mRNAs, na miRNAs zibaho cyane kandi zikagira uruhare runini mu iterambere rya kanseri.Hano hari ibimenyetso byinshi byerekana uruhare rukomeye rwa mRNA cyangwa miRNA mu guhanura ubuzima rusange muri kanseri zitandukanye.Nta gushidikanya, ibyitegererezo byinshi byerekana ingaruka nabyo bishingiye kuri lncRNAs.Kurugero, Luo n'abandi.Ubushakashatsi bwerekanye ko LINC01094 igira uruhare runini mu gukwirakwiza PC na metastasis, kandi imvugo ya LINC01094 ikagaragaza ubuzima bubi bw’abarwayi ba kanseri yandura [16].Ubushakashatsi bwatanzwe na Lin n'abandi.Ubushakashatsi bwerekanye ko kugabanya lncRNA FLVCR1-AS1 bifitanye isano no kutamenya neza abarwayi ba kanseri yandura [17].Nyamara, lncRNAs zijyanye n'ubudahangarwa usanga zaganiriweho cyane mubijyanye no guhanura muri rusange abarwayi ba kanseri.Vuba aha, imirimo myinshi yibanze ku kubaka icyitegererezo cy’ingaruka zo guhanura ubuzima bwa abarwayi ba kanseri bityo bigahindura uburyo bwo kuvura [18, 19, 20].Hariho kumenyekanisha uruhare rukomeye rwumudugudu winjira mugutangiza kanseri, gutera imbere, no gusubiza imiti nka chimiotherapie.Ubushakashatsi bwinshi bwemeje ko ingirangingo z'umubiri zinjira mu kibyimba zigira uruhare runini mu gusubiza imiti ya cytotoxic [21, 22, 23].Ibibyimba birinda microen ibidukikije ni ikintu cyingenzi mu mibereho y’abarwayi b’ibibyimba [24, 25].Immunotherapy, cyane cyane ivura ICI, ikoreshwa cyane mu kuvura ibibyimba bikomeye [26].Imirasire ijyanye na immun ikoreshwa cyane mukubaka ibyitegererezo byerekana ingaruka.Kurugero, Su n'abandi.Icyitegererezo cy’ingaruka ziterwa n’ubudahangarwa bushingiye ku ngirabuzimafatizo za poroteyine kugira ngo hamenyekane neza abarwayi ba kanseri y’intanga [27].Ingirabuzimafatizo zidafite kode nka lncRNAs nazo zirakwiriye mu kubaka icyitegererezo cy’ingaruka zishobora kubaho [28, 29, 30].Luo n'abandi bapimishije lncRNAs enye zijyanye n'ubudahangarwa kandi bubaka icyitegererezo cyo guhanura kanseri y'inkondo y'umura [31].Khan n'abandi.Hamenyekanye inyandiko-mvugo 32 zitandukanye mu buryo butandukanye, kandi hashingiwe kuri ibyo, hashyizweho uburyo bwo guhanura hamwe n’inyandiko 5 z’ingenzi, bwatanzwe nk’igikoresho cyasabwe cyane mu guhanura biopsy yemejwe no kwangwa nyuma yo guterwa impyiko [32].
Byinshi muribi byitegererezo bishingiye ku miterere ya gene, yaba gen-protein-coding cyangwa gen-code.Nyamara, gene imwe irashobora kugira indangagaciro zitandukanye muri genome zitandukanye, imiterere yamakuru ndetse no mubarwayi batandukanye, biganisha ku mibare idahwitse muburyo bwo guhanura.Muri ubu bushakashatsi, twubatse icyitegererezo cyumvikana hamwe na joriji ebyiri za lncRNAs, tutisunze indangagaciro nyayo zerekana.
Muri ubu bushakashatsi, twabonye irlncRNA kunshuro yambere dukoresheje isesengura rifitanye isano na genes zijyanye n'ubudahangarwa.Twerekanye 223 DEirlncRNAs muguhuza hamwe na lncRNAs zitandukanye.Icya kabiri, twubatse matrike 0-cyangwa-1 dushingiye ku buryo bwo guhuza DEirlncRNA bwatangajwe [31].Twahise dukora analyse univariate na lasso regression kugirango tumenye ibyateganijwe DEirlncRNA byombi hanyuma twubake icyitegererezo cyo guhanura.Twongeye gusesengura isano iri hagati y amanota yingaruka nibiranga ivuriro kubarwayi barwaye PAAD.Twabonye ko icyitegererezo cyibyago byerekana, nkibintu byigenga byerekana abarwayi ba PAAD, bishobora gutandukanya neza abarwayi bo mu rwego rwo hejuru n’abarwayi bo mu rwego rwo hasi n’abarwayi bo mu rwego rwo hejuru n’abarwayi bo mu rwego rwo hasi.Byongeye kandi, indangagaciro za AUC zerekana umurongo wa ROC zerekana ingaruka zishobora guterwa ni 0.905 kubiteganijwe umwaka 1, 0.942 kubiteganijwe mu myaka 2, na 0.966 kubiteganijwe mu myaka 3.
Abashakashatsi bavuze ko abarwayi bafite CD8 + T yinjira cyane mu ngirabuzimafatizo bumva neza ubuvuzi bwa ICI [33].Ubwiyongere bwibiri muri selile cytotoxic, CD56 NK selile, NK selile na CD8 + T mumyanya mikorobe ikingira ikibyimba bishobora kuba imwe mumpamvu zitera ingaruka zo guhagarika ikibyimba [34].Ubushakashatsi bwibanze bwerekanye ko urwego rwo hejuru rwa CD4 (+) T na CD8 (+) T rwagize uruhare runini mu kubaho igihe kirekire [35].Kwinjira kwa selile CD8 T, umutwaro muke wa neoantigen, hamwe na microen ibidukikije ikingira indwara ikingira indwara itera kutitabira imiti ya ICI [36].Twabonye ko amanota yingaruka yari afitanye isano nabi na selile CD8 + T na selile NK, byerekana ko abarwayi bafite amanota menshi ashobora kuba badakwiriye kuvurwa na ICI kandi bafite prognoz mbi.
CD161 ni ikimenyetso cyica selile (NK) selile.CD8 + CD161 + CAR-yandujwe na T selile ihuza imbaraga muri vivo antitumor efficacy muri HER2 + pancreatic ductal adenocarcinoma xenograft yerekana [37].Immune igenzura ibuza cytotoxic T lymphocyte ifitanye isano na poroteyine 4 (CTLA-4) hamwe na poroteyine y'urupfu rwa selile 1 (PD-1) / porogaramu y'urupfu rwa selile ligand 1 (PD-L1) kandi ifite imbaraga nyinshi mubice byinshi.Kugaragaza CTLA-4 na CD161 (KLRB1) biri hasi mumatsinda afite ibyago byinshi, bikomeza byerekana ko abarwayi bafite amanota menshi ashobora kutemererwa kuvurwa na ICI.[38]
Kugirango tubone uburyo bwo kuvura bubereye abarwayi bafite ibyago byinshi, twasesenguye imiti itandukanye ya anticancer dusanga paclitaxel, sorafenib, na erlotinib, zikoreshwa cyane kubarwayi barwaye PAAD, zishobora kuba zibereye abarwayi bafite ibyago byinshi bafite PAAD.[33].Zhang n'abandi basanze ihinduka ry’imihindagurikire y’inzira zose zangiza ADN (DDR) rishobora gutuma umuntu atamenya neza abarwayi ba kanseri ya prostate [39].Ikigeragezo cya Kanseri ya Pancreatic Olaparib Ikomeje (POLO) cyerekanye ko kuvura hamwe na olaparib igihe kirekire cyo kubaho nta terambere ugereranije na placebo nyuma ya chimiotherapie yo mu murongo wa mbere wa platine ku barwayi bafite pancreatic ductal adenocarcinoma na germine BRCA1 / 2 ihinduka [40].Ibi bitanga icyizere gikomeye ko ibisubizo byubuvuzi bizatera imbere cyane muri iri tsinda ry abarwayi.Muri ubu bushakashatsi, agaciro ka IC50 ka AZD.2281 (olaparib) kari hejuru mu itsinda ry’ibyago byinshi, byerekana ko abarwayi ba PAAD bo mu itsinda ry’ibyago byinshi bashobora kwihanganira kwivuza hamwe na AZD.2281.
Uburyo bwo guhanura muri ubu bushakashatsi butanga ibisubizo byiza byo guhanura, ariko bishingiye kubisesengura.Nigute ushobora kwemeza ibisubizo hamwe namakuru yubuvuzi nikibazo cyingenzi.Endoscopique nziza y'urushinge aspirasi ultrasonography (EUS-FNA) yahindutse uburyo bwingenzi bwo gusuzuma ibikomere bikomeye kandi bidasanzwe byitwa pancreatic pancreatic bifite sensibilité ya 85% kandi byihariye bya 98% [41].Kuza kwa urushinge rwa EUS rwiza-urushinge (EUS-FNB) rushingiye ahanini ku nyungu zigaragara kurenza FNA, nko kumenya neza niba kwisuzumisha neza, kubona ingero zibungabunga imiterere y’amateka, bityo bikabyara ingirangingo z'umubiri zifite akamaro kanini mu gusuzuma.umwanda udasanzwe [42].Isubiramo rifatika ry’ubuvanganzo ryemeje ko inshinge za FNB (cyane cyane 22G) zigaragaza imikorere myiza yo gusarura ingirabuzimafatizo ziva mu mitsi ya pancreatic [43].Mubuvuzi, umubare muto wabarwayi ni bo bemerewe kubagwa bikabije, kandi abarwayi benshi bafite ibibyimba bidashoboka mugihe cyo kwisuzumisha bwa mbere.Mubikorwa byubuvuzi, umubare muto wabarwayi ubereye kubagwa bikabije kuko abarwayi benshi bafite ibibyimba bidashoboka mugihe cyo kwisuzumisha bwa mbere.Nyuma yo kwemezwa na patologi na EUS-FNB nubundi buryo, ubuvuzi busanzwe butari kubaga nka chimiotherapie burahitamo.Gahunda yacu y'ubushakashatsi ikurikira ni ukugerageza icyitegererezo cy'ubu bushakashatsi muri cohort yo kubaga no kubaga binyuze mu isesengura ryihuse.
Muri rusange, ubushakashatsi bwacu bwashyizeho uburyo bushya bwo kumenya ingaruka zishingiye kuri irlncRNA zombi, zerekanaga agaciro keza ko gutangaza abarwayi barwaye kanseri yandura.Icyitegererezo cyibyago bishobora gufasha gutandukanya abarwayi bafite PAAD babereye kwivuza.
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Igihe cyo kohereza: Nzeri-22-2023