ʻO ka maʻi ʻaʻai pancreatic kekahi o nā maʻi maʻi ʻoi loa i ka honua me kahi prognosis maikaʻi ʻole.No laila, pono ke ʻano wānana pololei e ʻike ai i nā poʻe maʻi i ka nui o ka maʻi maʻi pancreatic e hoʻoponopono i ka mālama ʻana a hoʻomaikaʻi i ka wānana o kēia mau maʻi.
Loaʻa iā mākou ka ʻikepili ʻo The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) RNAseq mai ka waihona UCSC Xena, i ʻike ʻia nā lncRNAs pili i ka immune (irlncRNAs) ma o ka hoʻopili ʻana, a ʻike i nā ʻokoʻa ma waena o TCGA a me nā ʻiʻo adenocarcinoma pancreatic maʻamau.DEirlncRNA) mai ka TCGA a me ka genotype tissue expression (GTEx) o ka ʻiʻo pancreatic.Ua hana ʻia nā loiloi univariate a me ka laso regression e kūkulu i nā hiʻohiʻona pūlima prognostic.A laila, helu mākou i ka ʻāpana ma lalo o ka pihi a hoʻoholo i ka waiwai cutoff maikaʻi loa no ka ʻike ʻana i nā maʻi me ka adenocarcinoma pancreatic kiʻekiʻe a haʻahaʻa.No ka hoʻohālikelike ʻana i nā hiʻohiʻona lapaʻau, ka infiltration cell immune, immunosuppressive microenvironment, a me ka pale ʻana i ka chemotherapy i nā maʻi me ka maʻi maʻi pancreatic kiʻekiʻe a haʻahaʻa.
Ua ʻike mākou he 20 DEirlncRNA mau pālua a hui pū ʻia nā maʻi e like me ka waiwai cutoff maikaʻi loa.Ua hōʻike mākou he hana koʻikoʻi kā mākou hōʻailona hōʻailona prognostic i ka wānana i ka prognosis o nā maʻi me PAAD.ʻO ka AUC o ka pihi ROC he 0.905 no ka wānana 1 makahiki, 0.942 no ka wānana 2 makahiki, a me 0.966 no ka wānana 3 makahiki.Loaʻa i nā poʻe maʻi koʻikoʻi ke ola haʻahaʻa a ʻoi aku ka maikaʻi o nā ʻano lapaʻau.Ua hōʻike pū mākou he immunosuppressed nā poʻe maʻi kiʻekiʻe a hiki ke hoʻomohala i ke kū'ē i ka immunotherapy.ʻO ka loiloi o nā lāʻau anticancer e like me ka paclitaxel, sorafenib, a me ka erlotinib e pili ana i nā mea hana wānana helu e kūpono paha i nā poʻe maʻi kiʻekiʻe me ka PAAD.
ʻO ka holoʻokoʻa, ua hoʻokumu kā mākou noiʻi i kahi kumu hoʻohālikelike prognostic hou e pili ana i ka irlncRNA paired, ka mea i hōʻike i ka waiwai prognostic hoʻohiki i nā mea maʻi me ka maʻi maʻi pancreatic.Hiki i kā mākou kumu hoʻohālikelike prognostic ke kōkua i ka hoʻokaʻawale ʻana i nā poʻe maʻi me PAAD i kūpono no ka mālama olakino.
ʻO ka maʻi ʻaʻai pancreatic kahi maʻi maʻi maʻi me ka haʻahaʻa haʻahaʻa haʻahaʻa ola ʻelima mau makahiki a kiʻekiʻe.I ka manawa o ka hōʻoia ʻana, aia ka hapa nui o nā maʻi i nā pae holomua.I ka pōʻaiapili o ka maʻi maʻi COVID-19, aia nā kauka a me nā kahu hānai ma lalo o ke koʻikoʻi nui i ka wā e mālama ai i nā mea maʻi me ka maʻi maʻi pancreatic, a ke alo pū nei nā ʻohana o nā mea maʻi i nā pilikia he nui i ka wā e hoʻoholo ai i ka mālama ʻana [1, 2].ʻOiai ua loaʻa nā holomua nui i ka mālama ʻana i nā DOAD, e like me ka neoadjuvant therapy, ka ʻoki ʻoki ʻana, ka radiation therapy, ka chemotherapy, ka molecular therapy, a me ka immune checkpoint inhibitors (ICIs), aia wale nō ma kahi o 9% o nā maʻi e ola i ʻelima mau makahiki ma hope o ka maʻi. ].], 4].No ka mea he atypical nā hōʻailona mua o ka pancreatic adenocarcinoma, ʻike pinepine ʻia nā mea maʻi me nā metastases ma kahi pae kiʻekiʻe [5].No laila, no ka mea maʻi i hāʻawi ʻia, pono e noʻonoʻo ka mālama ʻana i nā pono a me nā hemahema o nā koho lapaʻau āpau, ʻaʻole wale e hoʻolōʻihi i ke ola, akā e hoʻomaikaʻi i ka maikaʻi o ke ola [6].No laila, pono ke kŘkohu wanana kūpono no ka loiloi pono i ka wānana o ka mea ma'i [7].No laila, hiki ke koho ʻia ka lāʻau kūpono e kaulike i ke ola a me ka maikaʻi o ke ola o nā maʻi me PAAD.
ʻO ka wānana maikaʻi ʻole o PAAD ma muli o ke kūʻē ʻana i nā lāʻau lapaʻau chemotherapy.I nā makahiki i hala iho nei, ua hoʻohana nui ʻia nā mea hoʻopaʻapaʻa i ka pale ʻana i nā maʻi maʻi paʻa [8].Eia nō naʻe, ʻaʻole kūleʻa ka hoʻohana ʻana o ICI i ka maʻi maʻi pancreatic [9].No laila, he mea nui e ʻike i nā poʻe maʻi e pōmaikaʻi mai ka ICI therapy.
ʻO RNA non-coding lōʻihi (lncRNA) he ʻano RNA non-coding me nā transcripts >200 nucleotides.Laha ʻia nā LncRNA a ʻo ia ka 80% o ka transcriptome kanaka [10].Ua hōʻike ʻia kahi kino nui o ka hana e hiki i nā hiʻohiʻona prognostic e pili ana i ka lncRNA ke wānana maikaʻi i ka wānana maʻi [11, 12].No ka laʻana, ua ʻike ʻia nā lncRNA e pili ana i ka autophagy e hana i nā inoa prognostic i ka maʻi maʻi umauma [13].Ua hoʻohana ʻia ʻeono mau lncRNA pili i ka immune e hoʻokumu i nā hiʻohiʻona prognostic o glioma [14].
I loko o ka maʻi maʻi pancreatic, ua hoʻokumu kekahi mau haʻawina i nā pūlima e pili ana i ka lncRNA e wānana i ka wānana o ka maʻi.Ua hoʻokumu ʻia kahi pūlima 3-lncRNA i ka adenocarcinoma pancreatic me kahi wahi ma lalo o ka pihi ROC (AUC) o 0.742 wale nō a me ke ola holoʻokoʻa (OS) o 3 mau makahiki [15].Eia kekahi, ʻokoʻa nā waiwai hōʻike lncRNA ma waena o nā genomes like ʻole, nā ʻano ʻikepili like ʻole, a me nā maʻi like ʻole, a ʻaʻole paʻa ka hana o ke kumu wānana.No laila, hoʻohana mākou i kahi algorithm modeling novel, pairing and iteration, e hoʻohua i nā pūlima lncRNA (irlncRNA) pili i ka immunity e hana i kahi hoʻohālike wānana pololei a paʻa [8].
Ua loaʻa mai ka ʻikepili RNAseq maʻamau (FPKM) a me ka maʻi maʻi pancreatic maʻi TCGA a me ka genotype tissue expression (GTEx) mai ka waihona UCSC XENA (https://xenabrowser.net/datapages/).Ua loaʻa nā faila GTF mai ka waihona Ensembl (http://asia.ensembl.org) a hoʻohana ʻia no ka unuhi ʻana i nā moʻolelo hōʻike lncRNA mai RNAseq.Ua hoʻoiho mākou i nā genes pili i ka pale ʻana mai ka waihona ImmPort (http://www.immport.org) a ʻike i nā lncRNAs pili i ka immunity (irlncRNAs) me ka hoʻohana ʻana i ka loiloi correlation (p <0.001, r > 0.4).ʻO ka ʻike ʻana i nā irlncRNA i hōʻike ʻokoʻa ʻia (DEirlncRNAs) ma o ka hele ʻana i nā irlncRNAs a me nā lncRNA i hōʻike ʻokoʻa ʻia i loaʻa mai ka waihona GEPIA2 (http://gepia2.cancer-pku.cn/#index) ma ka hui TCGA-PAAD (|logFC| > 1 a me FDR ) <0.05).
Ua hōʻike mua ʻia kēia ʻano hana [8].Ma keʻano kikoʻī, kūkulu mākou iā X e pani i ka lncRNA A a me ka lncRNA B. Ke ʻoi aku ka nui o ka waiwai hōʻike o ka lncRNA A ma mua o ka waiwai hōʻike o lncRNA B, ua wehewehe ʻia ʻo X ʻo 1, inā ʻaʻole i wehewehe ʻia ʻo X he 0. No laila, hiki iā mākou ke loaʻa. he matrix o 0 a i ole – 1. O ka axis vertical o ka matrix e hoike ana i kela a me keia laana, a o ka axis horizontal e hoike ana i kela me keia DEirlncRNA pai me ka waiwai o 0 a i ole 1.
Ua hoʻohana ʻia ka loiloi regression univariate a ukali ʻia e Lasso regression e nānā i nā pālua DEirlncRNA prognostic.Ua hoʻohana ka lasso regression analysis i ka 10-fold cross-validation i hana hou ʻia i nā manawa 1000 (p <0.05), me 1000 random stimuli no ka holo.I ka wā i ʻoi aku ai ka pinepine o kēlā me kēia DEirlncRNA ma mua o 100 mau manawa i 1000 pōʻai, ua koho ʻia nā hui DEirlncRNA e kūkulu i kahi kumu hoʻohālike prognostic.A laila ua hoʻohana mākou i ka pihi AUC e ʻike i ka waiwai cutoff maikaʻi loa no ka hoʻokaʻawale ʻana i nā maʻi PAAD i nā pūʻulu kiʻekiʻe a haʻahaʻa.Ua helu pū ʻia ka waiwai AUC o kēlā me kēia kumu hoʻohālike a hoʻolālā ʻia ma ke ʻano he pihi.Inā piʻi ka piko i ka helu kiʻekiʻe loa e hōʻike ana i ka waiwai AUC kiʻekiʻe loa, pau ke kaʻina helu helu a manaʻo ʻia ke kumu hoʻohālike ka moho maikaʻi loa.Ua kūkulu ʻia nā hiʻohiʻona 1-, 3- a me 5-makahiki ROC curve.Ua hoʻohana ʻia nā loiloi regression univariate a me multivariate e nānā i ka hana wānana kūʻokoʻa o ke kumu hoʻohālike prognostic.
E hoʻohana i ʻehiku mau mea hana no ke aʻo ʻana i ka nui o ka infiltration cell immune, me XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, a me CIBERSORT.Ua hoʻoiho ʻia ka ʻikepili infiltration cell immune mai ka waihona TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Ua kālailai ʻia ka ʻokoʻa o ka maʻiʻo o nā pūnaewele hoʻokomo kino ma waena o nā pūʻulu kiʻekiʻe a me ka haʻahaʻa o ke kumu hoʻohālike i kūkulu ʻia me ka hoʻohana ʻana i ka hōʻike hōʻailona Wilcoxon, hōʻike ʻia nā hopena ma ka pakuhi square.Ua hana ʻia ʻo Spearman correlation analysis e nānā i ka pilina ma waena o nā helu helu pilikia a me nā cell immune-infiltrating.Hōʻike ʻia ka huina hoʻoponopono i loaʻa ma ke ʻano he lollipop.Ua kau ʻia ka paepae koʻikoʻi ma ka p <0.05.Ua hana ʻia ke kaʻina hana me ka R package ggplot2.No ka nānā ʻana i ka pilina ma waena o ke kumu hoʻohālike a me nā pae hōʻike gene e pili ana i ka helu o ka infiltration cell immune, ua hana mākou i ka ggstatsplot package a me ka violin plot visualization.
No ka loiloi ʻana i nā ʻano lapaʻau lapaʻau no ka maʻi maʻi pancreatic, ua helu mākou i ka IC50 o nā lāʻau lapaʻau maʻamau i hoʻohana ʻia ma ka hui TCGA-PAAD.Ua hoʻohālikelike ʻia nā ʻokoʻa i ka hapalua o nā ʻāpana inhibitory (IC50) ma waena o nā pūʻulu kiʻekiʻe a me nā haʻahaʻa haʻahaʻa me ka hoʻohana ʻana i ka hoʻāʻo ʻana i kau inoa ʻia e Wilcoxon, a hōʻike ʻia nā hopena e like me nā pahu pahu i hana ʻia me ka pRRophetic a me ggplot2 ma R. Hoʻopili nā ʻano a pau i nā alakaʻi a me nā loina kūpono.
Hōʻike ʻia ke kaʻina hana o kā mākou aʻo ʻana ma ka Figure 1. Ke hoʻohana nei i ka loiloi correlation ma waena o nā lncRNAs a me nā genes pili i ka immunity, ua koho mākou i 724 irlncRNAs me ka p <0.01 a me r> 0.4.Ua nānā hou mākou i nā lncRNA i hōʻike ʻia o GEPIA2 (Figure 2A).He 223 irlncRNA i hōʻike ʻokoʻa ʻia ma waena o ka adenocarcinoma pancreatic a me ka ʻiʻo pancreatic maʻamau (| logFC| > 1, FDR <0.05), i kapa ʻia ʻo DEirlncRNAs.
Ke kūkulu ʻana i nā hiʻohiʻona pōʻino wānana.(A) ʻāpana pele o nā lncRNA hōʻike ʻokoʻa.(B) Ka puunaue ana o ka laso coefficients no 20 DEirlncRNA pai.(C) Ka ʻokoʻa likelihood hapa o ka puʻunaue helu LASSO.(D) E hōʻike ana ka ʻāpana ulu lāʻau e hōʻike ana i ka loiloi regression univariate o 20 DEirlncRNA mau pālua.
Ua kūkulu hou mākou i kahi matrix 0 a i ʻole 1 ma ka hoʻopili ʻana i 223 DEirlncRNAs.Ua ʻike ʻia he 13,687 mau pālua DEirlncRNA.Ma hope o ka loiloi univariate a me ka lasso regression, ua hoʻāʻo hope ʻia ʻo 20 DEirlncRNA pai e kūkulu i kahi kumu hoʻohālikelike prognostic (Figure 2B-D).Ma muli o nā hopena o Lasso a me ka loiloi regression he nui, ua helu mākou i kahi helu pilikia no kēlā me kēia maʻi ma ka TCGA-PAAD cohort (Table 1).Ma muli o nā hopena o ka lasso regression analysis, ua helu mākou i kahi helu pilikia no kēlā me kēia maʻi ma ka TCGA-PAAD cohort.ʻO ka AUC o ka pihi ROC he 0.905 no ka wanana hoʻohālike 1-makahiki, 0.942 no ka wānana 2-makahiki, a me 0.966 no ka wānana 3-makahiki (Figure 3A-B).Hoʻonohonoho mākou i kahi waiwai cutoff maikaʻi loa o 3.105, hoʻokaʻawale i nā maʻi cohort TCGA-PAAD i nā pūʻulu kiʻekiʻe a me nā haʻahaʻa haʻahaʻa, a hoʻolālā i nā hopena ola a me nā puʻu helu pilikia no kēlā me kēia maʻi (Figure 3C-E).Ua hōʻike ʻo Kaplan-Meier i ke ola ʻana o ka poʻe maʻi PAAD i ka pūʻulu kiʻekiʻe ma mua o ka poʻe maʻi i ka hui haʻahaʻa haʻahaʻa (p <0.001) (Figure 3F).
Pono o nā kumu hoʻohālike prognostic.(A) ROC o ke kumu hoʻohālike prognostic.(B) 1-, 2-, a me 3 makahiki ROC prognostic hoʻohālike.(C) ROC o ke kumu hoʻohālike prognostic.Hōʻike i ka ʻoki ʻoki maikaʻi loa.(DE) Ka mahele ʻana o ke kūlana ola (D) a me nā helu pilikia (E).(F) Kaplan-Meier loiloi o nā maʻi PAAD i nā hui kiʻekiʻe a me nā haʻahaʻa haʻahaʻa.
Ua loiloi hou mākou i nā ʻokoʻa o nā helu pilikia e nā ʻano lapaʻau.Hōʻike ka ʻāpana ʻāpana (Figure 4A) i ka pilina holoʻokoʻa ma waena o nā ʻano lapaʻau a me nā helu pilikia.ʻO ka mea nui, ua loaʻa i nā poʻe maʻi kahiko nā helu pilikia (Figure 4B).Eia kekahi, ʻoi aku ka nui o nā helu pilikia ma mua o nā maʻi me ka pae I (Figure 4C).E pili ana i ka pae maʻi maʻi maʻi PAAD, ʻoi aku ka nui o nā maʻi maʻi 3 ma mua o nā maʻi maʻi 1 a me 2 (Figure 4D).Ua hana hou mākou i nā loiloi univariate a me multivariate regression a hōʻike i ka helu pilikia (p <0.001) a me nā makahiki (p = 0.045) he mau mea kūʻokoʻa prognostic i nā maʻi me PAAD (Figure 5A-B).Ua hōʻike ka ʻaoʻao ROC ua ʻoi aku ka maikaʻi o ka helu pilikia ma mua o nā ʻano lapaʻau ʻē aʻe i ka wānana 1-, 2-, a me 3-makahiki ola o nā maʻi me PAAD (Figure 5C-E).
Nā hiʻohiʻona maʻi o nā kumu hoʻohālike prognostic.Hōʻike ka histogram (A) i (B) makahiki, (C) pae maʻi tumora, (D) pae maʻi, helu pilikia, a me ke kāne o nā maʻi ma ka hui TCGA-PAAD.**p < 0.01
Ka nānā 'ana wanana kū'oko'a o nā kumu ho'ohālike prognostic.(AB) Univariate (A) and multivariate (B) regression analysis of prognostic risk models and clinical features.(CE) 1-, 2-, a me 3-makahiki ROC no nā hiʻohiʻona pilikia prognostic a me nā ʻano lapaʻau.
No laila, ua nānā mākou i ka pilina ma waena o ka manawa a me nā helu pilikia.Ua ʻike mākou i ka helu pilikia i nā maʻi PAAD i hoʻopili ʻia me nā cell CD8 + T a me nā pūnaewele NK (Figure 6A), e hōʻike ana i ka hoʻopaʻa ʻana i ka hana immune i ka hui kiʻekiʻe.Ua loiloi pū mākou i ka ʻokoʻa o ka infiltration cell immune ma waena o nā hui kiʻekiʻe a me ka haʻahaʻa haʻahaʻa a loaʻa nā hopena like (Figure 7).Ua emi iho ka infiltration o CD8+ T cell a me NK cell i loko o ka pūʻulu pilikia.I nā makahiki i hala iho nei, ua hoʻohana nui ʻia nā mea hoʻopaʻapaʻa hoʻomaʻamaʻa immune (ICI) i ka mālama ʻana i nā maʻi maʻi paʻa.Eia naʻe, ʻaʻole i kūleʻa ka hoʻohana ʻana i nā ICI i ka maʻi maʻi pancreatic.No laila, ua loiloi mākou i ka hōʻike ʻana o nā genes checkpoint immune i nā pūʻulu kiʻekiʻe a haʻahaʻa.Uaʻike mākou ua hoʻonuiʻia ka CTLA-4 a me CD161 (KLRB1) i ka hui haʻahaʻa haʻahaʻa (Figure 6B-G), e hōʻike ana i nā maʻi PAAD i ka hui haʻahaʻa haʻahaʻa hiki ke maʻalahi i ka ICI.
Ka hoʻoponopono hoʻoponopono o ka prognostic risk model and immune cell infiltration.(A) Ka pilina ma waena o ke kumu hoʻohālikelike prognostic a me ka hoʻokomo ʻana o nā cell immune.(BG) Hōʻike i ka hōʻike gene i nā pūʻulu pilikia nui a haʻahaʻa.(HK) IC50 waiwai no nā lāʻau anticancer kūikawā i nā hui kiʻekiʻe a haʻahaʻa.*p <0.05, **p <0.01, ns = ʻaʻole koʻikoʻi
Ua loiloi hou mākou i ka hui ma waena o nā helu pilikia a me nā mea hana chemotherapy maʻamau i ka TCGA-PAAD cohort.Ua ʻimi mākou i nā lāʻau anticancer maʻamau i ka maʻi maʻi pancreatic a nānā i nā ʻokoʻa i kā lākou mau waiwai IC50 ma waena o nā hui kiʻekiʻe a me nā haʻahaʻa haʻahaʻa.Ua hōʻike nā hualoaʻa i ka waiwai IC50 o AZD.2281 (olaparib) iʻoi aku ka kiʻekiʻe ma ka hui kiʻekiʻe, e hōʻike ana i nā poʻe maʻi PAAD i ka hui kiʻekiʻe ke kū'ē i ka lāʻau AZD.2281 (Figure 6H).Eia kekahi, ʻoi aku ka haʻahaʻa o nā koina IC50 o paclitaxel, sorafenib, a me erlotinib i ka hui kiʻekiʻe (Figure 6I-K).Ua ʻike hou mākou i nā lāʻau lapaʻau anticancer 34 me nā koina IC50 kiʻekiʻe i ka hui kiʻekiʻe a me nā lāʻau anticancer 34 me nā koina IC50 haʻahaʻa i ka hui kiʻekiʻe (Table 2).
ʻAʻole hiki ke hōʻole ʻia ka nui o nā lncRNAs, mRNAs, a me miRNAs a he hana koʻikoʻi i ka ulu ʻana o ka maʻi kanesa.Nui nā hōʻike e kākoʻo ana i ke kuleana koʻikoʻi o ka mRNA a i ʻole ka miRNA i ka wānana ʻana i ke ola holoʻokoʻa i nā ʻano maʻi kanesa.ʻAʻole kānalua, nui nā kumu hoʻohālike prognostic e pili ana i nā lncRNA.Eia kekahi laʻana, Luo et al.Ua hōʻike nā haʻawina he mea nui ka LINC01094 i ka hoʻonui ʻana o PC a me ka metastasis, a ʻo ka ʻōlelo kiʻekiʻe o LINC01094 e hōʻike ana i ke ola maikaʻi ʻole o nā maʻi maʻi maʻi pancreatic [16].ʻO ka haʻawina i hōʻike ʻia e Lin et al.Ua hōʻike nā haʻawina e pili ana ka downregulation o lncRNA FLVCR1-AS1 me ka prognosis maikaʻi ʻole i nā maʻi maʻi maʻi pancreatic [17].Eia nō naʻe, ʻaʻole i kūkākūkā nui ʻia nā lncRNA pili i ka immunity e pili ana i ka wānana i ke ola holoʻokoʻa o nā maʻi maʻi maʻi.I kēia mau lā, ua nui ka nui o ka hana i ke kūkulu ʻana i nā hiʻohiʻona prognostic e wānana i ke ola o nā maʻi maʻi maʻi a no laila e hoʻoponopono i nā ʻano lapaʻau [18, 19, 20].Ke ulu nei ka hoʻomaopopo ʻana i ke kuleana nui o nā infiltrates immune i ka hoʻomaka ʻana o ka maʻi maʻi, ka holomua, a me ka pane ʻana i nā lāʻau lapaʻau e like me ka chemotherapy.Ua hōʻoia ka nui o nā noiʻi ʻana i ka nui o nā cell immune infiltrating tumor i ka pane ʻana i ka chemotherapy cytotoxic [21, 22, 23].ʻO ka tumor immune microenvironment kahi mea nui i ke ola o nā maʻi maʻi maʻi [24, 25].Hoʻohana nui ʻia ka Immunotherapy, ʻoi aku ka ICI therapy, i ka mālama ʻana i nā maʻi maʻi paʻa [26].Hoʻohana nui ʻia nā genes pili i ke kino no ke kūkulu ʻana i nā hiʻohiʻona prognostic risk.Eia kekahi laʻana, Su et al.Hoʻokumu ʻia ke kumu hoʻohālikelike prognostic pili i ka immune i nā genes-coding e wānana i ka wānana o nā maʻi maʻi ovarian [27].He kūpono hoʻi nā genes non-coding e like me lncRNAs no ke kūkulu ʻana i nā hiʻohiʻona prognostic risk [28, 29, 30].Ua hoʻāʻo ʻo Luo et al i ʻehā mau lncRNA pili i ka immune a kūkulu i kahi hiʻohiʻona wānana no ka maʻi kanesa cervical [31].ʻO Khan et al.Ua ʻike ʻia ka huina o 32 i hōʻike ʻia, a ma muli o kēia, ua hoʻokumu ʻia kahi hiʻohiʻona wānana me 5 mau transcripts koʻikoʻi, i manaʻo ʻia ma ke ʻano he mea hana i manaʻo ʻia no ka wānana ʻana i ka hōʻole ʻana i ka biopsy-hōʻoia ʻia ma hope o ka hoʻololi ʻana o ka kidney [32].
Hoʻokumu ʻia ka hapa nui o kēia mau hiʻohiʻona i nā pae hōʻike gene, nā genes-coding genes a i ʻole nā genes non-coding.Eia nō naʻe, hiki i ka gene like ke loaʻa i nā waiwai hōʻike like ʻole i nā genomes like ʻole, nā palapala ʻikepili a me nā maʻi like ʻole, e alakaʻi ana i nā kuhi paʻa ʻole i nā hiʻohiʻona wānana.I loko o kēia haʻawina, kūkulu mākou i kumu hoʻohālike kūpono me ʻelua mau lncRNA, kūʻokoʻa i nā waiwai hōʻike pololei.
Ma kēia noiʻi ʻana, ua ʻike mākou i ka irlncRNA no ka manawa mua ma o ka hoʻopili ʻana i ka hoʻopili ʻana me nā genes pili i ka immunity.Ua nānā mākou i nā DEirlncRNAs 223 e ka hybridization me nā lncRNA i hōʻike ʻokoʻa.ʻO ka lua, ua kūkulu mākou i kahi matrix 0-a-1 paha e pili ana i ke ʻano pairing DEirncRNA i paʻi ʻia [31].A laila, hana mākou i nā loiloi univariate a me ka laso regression e ʻike i nā pālua DEirlncRNA prognostic a kūkulu i kahi kumu hoʻohālikelike wānana.Hoʻopili hou mākou i ka hui ma waena o nā helu pilikia a me nā hiʻohiʻona maʻi i nā maʻi me PAAD.Ua ʻike mākou ʻo kā mākou hiʻohiʻona hoʻoweliweli prognostic, ma ke ʻano he kumu kūʻokoʻa kūʻokoʻa i nā maʻi PAAD, hiki ke hoʻokaʻawale maikaʻi i nā maʻi kiʻekiʻe mai nā maʻi haʻahaʻa a me nā maʻi kiʻekiʻe mai nā maʻi haʻahaʻa.Eia kekahi, ʻo nā waiwai AUC o ka pihi ROC o ke kumu hoʻohālikelike prognostic he 0.905 no ka wānana 1-makahiki, 0.942 no ka wānana 2-makahiki, a me 0.966 no ka wānana 3-makahiki.
Ua hōʻike nā mea noiʻi ua ʻoi aku ka maʻalahi o nā maʻi me ka CD8 + T cell infiltration kiʻekiʻe i ka mālama ICI [33].ʻO ka hoʻonui ʻana i ka ʻike o nā cell cytotoxic, CD56 NK cell, NK cell a me CD8 + T cell i ka tumor immune microenvironment ʻo ia paha kekahi o nā kumu o ka hopena suppressive tumor [34].Ua hōʻike ʻia nā haʻawina mua e pili nui ana nā pae kiʻekiʻe o ka CD4 (+) T a me CD8 (+) T me ke ola lōʻihi [35].ʻO ka CD8 T cell infiltration, haʻahaʻa neoantigen haʻahaʻa, a me kahi microenvironment tumor immunosuppressive nui e alakaʻi i ka nele o ka pane i ka ICI therapy [36].Ua ʻike mākou ua pili maikaʻi ʻole ka helu pilikia me nā pūnaewele CD8 + T a me nā pūnaewele NK, e hōʻike ana ʻaʻole kūpono nā maʻi me nā helu koʻikoʻi no ka mālama ʻana i ka ICI a ʻoi aku ka maikaʻi o ka prognosis.
ʻO CD161 kahi hōʻailona o nā pūnana pepehi kanaka maoli (NK).CD8+CD161+ CAR-transduced T cell mediate enhanced in vivo antitumor efficacy in HER2+ pancreatic ductal adenocarcinoma xenograft models [37].Hoʻopaʻa ʻia nā mea hoʻopaneʻe hoʻopaʻa kino i nā alahele cytotoxic T lymphocyte e pili ana i ka protein 4 (CTLA-4) a me ka programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) a loaʻa ka mana nui ma nā wahi he nui.ʻO ka hōʻikeʻana o CTLA-4 a me CD161 (KLRB1) he haʻahaʻa i nā pūʻulu kiʻekiʻe, e hōʻike ana i nā maʻi me nā helu kiʻekiʻe e hikiʻole ke kūpono i ka lāʻau ICI.[38]
No ka ʻimi ʻana i nā koho lapaʻau kūpono no nā poʻe maʻi kiʻekiʻe, ua ʻimi mākou i nā lāʻau anticancer like ʻole a ʻike i ka paclitaxel, sorafenib, a me erlotinib, i hoʻohana nui ʻia i nā poʻe maʻi me PAAD, hiki ke kūpono i nā maʻi kiʻekiʻe me ka PAAD.[33].Ua ʻike ʻo Zhang et al e hiki i ka hoʻololi ʻana i kekahi ala hōʻino DNA (DDR) ke alakaʻi i ka prognosis maikaʻi ʻole i nā maʻi maʻi prostate [39].Ua hōʻike ʻia ka hoʻokolohua Pancreatic Cancer Olaparib Ongoing (POLO) i ka mālama mālama ʻana me ka olaparib i hoʻolōʻihi i ke ola holomua ʻole me ka placebo ma hope o ka lāʻau lapaʻau platinum-based chemotherapy i nā maʻi me ka pancreatic ductal adenocarcinoma a me ka germline BRCA1/2 mutations [40].Hāʻawi kēia i ka manaʻo manaʻo nui e hoʻomaikaʻi maikaʻi nā hopena lapaʻau i kēia pūʻulu o nā maʻi.I loko o kēia haʻawina, ʻoi aku ka kiʻekiʻe o ka waiwai IC50 o AZD.2281 (olaparib) i ka hui kiʻekiʻe, e hōʻike ana i nā maʻi PAAD i ka hui kiʻekiʻe e kūʻē i ka mālama ʻana me AZD.2281.
ʻO nā hiʻohiʻona wānana i kēia haʻawina e hoʻopuka i nā hopena wānana maikaʻi, akā ua hoʻokumu ʻia lākou ma nā wānana analytical.Pehea e hōʻoia ai i kēia mau hopena me ka ʻikepili lapaʻau he nīnau koʻikoʻi.Ua lilo ʻo Endoscopic fine needle aspiration ultrasonography (EUS-FNA) i mea koʻikoʻi no ka hoʻomaʻamaʻa ʻana i nā maʻi pancreatic paʻa a me ka extrapancreatic me ka sensitivity o 85% a me ka kikoʻī o 98% [41].ʻO ka hiki ʻana mai o nā kola biopsy maikaʻi ʻo EUS (EUS-FNB) ma muli o nā pono i ʻike ʻia ma luna o FNA, e like me ke kiʻekiʻe o ka diagnostic pololei, ka loaʻa ʻana o nā laʻana e mālama ai i ke ʻano histological, a pēlā e hoʻoulu ai i ka ʻiʻo immune i koʻikoʻi no kekahi mau maʻi.hoʻopaʻa ʻia [42].Ua hōʻike ʻia kahi loiloi ʻōnaehana o ka palapala e hōʻike ana nā kola FNB (ʻoi aku ka 22G) i ka hana kiʻekiʻe loa i ka ʻohi ʻana i nā kiko mai ka pancreatic masses [43].ʻO ka maʻi maʻi, he liʻiliʻi wale nō o nā mea maʻi i kūpono no ka hōʻoki radical, a ʻo ka hapa nui o nā maʻi i loaʻa i nā maʻi ʻaʻole hiki ke hoʻohana ʻia i ka manawa o ka ʻike mua.Ma ka hoʻomaʻamaʻa hoʻomaʻamaʻa, he hapa liʻiliʻi wale nō o nā maʻi i kūpono no ke kaʻina radical no ka mea ʻo ka hapa nui o nā maʻi i loaʻa nā maʻi ʻaʻole hiki ke hoʻohana ʻia i ka manawa o ka ʻike mua.Ma hope o ka hōʻoia ʻana o ka pathological e EUS-FNB a me nā ʻano hana ʻē aʻe, koho maʻamau ka mālama ʻana i ka non-surgical e like me ka chemotherapy.ʻO kā mākou papahana noiʻi hope e hoʻāʻo i ka hiʻohiʻona prognostic o kēia haʻawina i nā cohorts ʻokiʻoki a me ka nonsurgical ma o ka loiloi retrospective.
ʻO ka holoʻokoʻa, ua hoʻokumu kā mākou noiʻi i kahi kumu hoʻohālikelike prognostic hou e pili ana i ka irlncRNA paired, ka mea i hōʻike i ka waiwai prognostic hoʻohiki i nā mea maʻi me ka maʻi maʻi pancreatic.Hiki i kā mākou kumu hoʻohālikelike prognostic ke kōkua i ka hoʻokaʻawale ʻana i nā poʻe maʻi me PAAD i kūpono no ka mālama olakino.
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Ka manawa hoʻouna: Sep-22-2023