ʻO ke kanesa pancreatic kekahi o nā puʻupuʻu make loa ma ka honua me ka wānana maikaʻi ʻole. No laila, pono kahi kumu hoʻohālike wānana pololei e ʻike i nā poʻe maʻi i ka pilikia kiʻekiʻe o ka maʻi kanesa pancreatic e hoʻopilikino i ka lāʻau a hoʻomaikaʻi i ka wānana o kēia mau maʻi.
Ua loaʻa iā mākou ka ʻikepili RNAseq o ka Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) mai ka waihona ʻikepili UCSC Xena, ua ʻike ʻia nā lncRNA pili i ka pale ʻana (irlncRNAs) ma o ka nānā ʻana i ka pilina, a ua ʻike ʻia nā ʻokoʻa ma waena o TCGA a me nā ʻiʻo adenocarcinoma pancreatic maʻamau. DEirlncRNA) mai TCGA a me ka genotype tissue expression (GTEx) o ka ʻiʻo pancreatic. Ua hana hou ʻia nā loiloi regression univariate a me lasso e kūkulu i nā hiʻohiʻona hōʻailona prognostic. A laila ua helu mākou i ka wahi ma lalo o ke kūlou a ua hoʻoholo i ka waiwai cutoff kūpono no ka ʻike ʻana i nā maʻi me ka adenocarcinoma pancreatic kiʻekiʻe a me ka haʻahaʻa. No ka hoʻohālikelike ʻana i nā ʻano lapaʻau, ka infiltration cell immune, ka microenvironment immunosuppressive, a me ke kūʻē ʻana i ka chemotherapy i nā maʻi me ka maʻi kanesa pancreatic kiʻekiʻe a me ka haʻahaʻa.
Ua ʻike mākou i 20 mau hui DEirlncRNA a ua hoʻohui pū i nā maʻi e like me ka waiwai cutoff kūpono. Ua hōʻike mākou he hana koʻikoʻi ko kā mākou kumu hoʻohālike prognostic i ka wānana ʻana i ka prognosis o nā maʻi me PAAD. ʻO ka AUC o ka piʻo 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. ʻOi aku ka haʻahaʻa o nā helu ola o nā maʻi kiʻekiʻe a ʻoi aku ka ʻino o nā ʻano lapaʻau. Ua hōʻike pū mākou ua pale ʻia nā maʻi kiʻekiʻe a hiki ke hoʻomohala i ke kūʻē ʻana i ka immunotherapy. ʻO ka loiloi ʻana o nā lāʻau anticancer e like me paclitaxel, sorafenib, a me erlotinib e pili ana i nā mea hana wānana computational e kūpono paha no nā maʻi kiʻekiʻe me PAAD.
Ma keʻano holoʻokoʻa, ua hoʻokumu kā mākou noiʻi i kahi kumu hoʻohālike pilikia prognostic hou e pili ana i ka irlncRNA i hui pū ʻia, kahi i hōʻike i ka waiwai prognostic hoʻohiki i nā poʻe maʻi me ka maʻi ʻaʻai pancreatic. Hiki i kā mākou kumu hoʻohālike pilikia prognostic ke kōkua i ka hoʻokaʻawale ʻana i nā poʻe maʻi me PAAD i kūpono no ka mālama lapaʻau.
He puʻupuʻu ʻino ka maʻi ʻaʻai pancreatic me ka haʻahaʻa o ka nui o ke ola ʻana no ʻelima mau makahiki a me ke kiʻekiʻe. I ka manawa o ka ʻike ʻana, aia ka hapa nui o nā maʻi i nā pae holomua. I loko o ke ahulau COVID-19, aia nā kauka a me nā kahu maʻi ma lalo o ke kaomi nui i ka wā e mālama ai i nā maʻi me ke kanesa pancreatic, a ke kū nei hoʻi nā ʻohana o nā maʻi i nā kaomi he nui i ka wā e hoʻoholo ai i ka mālama ʻana [1, 2]. ʻOiai ua holomua nui ka mālama ʻana i nā DOAD, e like me ka neoadjuvant therapy, surgical resection, radiation therapy, chemotherapy, targeted molecular therapy, a me nā immune checkpoint inhibitors (ICIs), aia wale nō ma kahi o 9% o nā maʻi e ola ana i ʻelima mau makahiki ma hope o ka ʻike ʻana [3]. ], 4]. No ka mea, he atypical nā hōʻailona mua o ka pancreatic adenocarcinoma, ʻike pinepine ʻia nā maʻi me nā metastases i kahi pae holomua [5]. No laila, no kahi maʻi i hāʻawi ʻia, pono e kaupaona ka mālama piha pilikino i nā pono a me nā hemahema o nā koho lapaʻau āpau, ʻaʻole wale no ka hoʻolōʻihi ʻana i ke ola, akā no ka hoʻomaikaʻi ʻana i ke ʻano o ke ola [6]. No laila, pono kahi kumu hoʻohālike wānana kūpono e loiloi pololei i ka prognosis o ka mea maʻi [7]. No laila, hiki ke koho ʻia ka lāʻau kūpono e kaulike i ke ola a me ke ʻano o ke ola o nā maʻi me PAAD.
ʻO ka wānana maikaʻi ʻole o PAAD ma muli nui o ke kūʻē ʻana i nā lāʻau chemotherapy. I nā makahiki i hala iho nei, ua hoʻohana nui ʻia nā mea hoʻopaʻa checkpoint immune i ka mālama ʻana i nā tumors paʻa [8]. Eia nō naʻe, ʻaʻole i kūleʻa ka hoʻohana ʻana i nā ICI i ka maʻi kanesa pancreatic [9]. No laila, he mea nui e ʻike i nā poʻe maʻi e pōmaikaʻi paha mai ka lāʻau ICI.
ʻO ka RNA lōʻihi non-coding (lncRNA) kahi ʻano RNA non-coding me nā transcripts >200 nucleotides. He laha nā LncRNA a he 80% o ka transcriptome kanaka [10]. Ua hōʻike ʻia kahi nui o nā hana e hiki i nā hiʻohiʻona prognostic i hoʻokumu ʻia e lncRNA ke wānana pono i ka prognosis o ka mea maʻi [11, 12]. No ka laʻana, ua ʻike ʻia he 18 mau lncRNA e pili ana i ka autophagy e hana i nā pūlima prognostic i ka maʻi ʻaʻai umauma [13]. ʻEono mau lncRNA e pili ana i ka pale ʻana i hoʻohana ʻia e hoʻokumu i nā hiʻohiʻona prognostic o glioma [14].
I loko o ke kanesa pancreatic, ua hoʻokumu kekahi mau noiʻi i nā pūlima lncRNA e wānana i ka prognosis o ka mea maʻi. Ua hoʻokumu ʻia kahi pūlima 3-lncRNA i loko o ka adenocarcinoma pancreatic me kahi wahi ma lalo o ke kiʻikuhi 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 mea maʻi like ʻole, a ʻaʻole paʻa ka hana o ke kumu hoʻohālike wānana. No laila, hoʻohana mākou i kahi algorithm hoʻohālike hou, pairing a me iteration, e hana i nā pūlima lncRNA (irlncRNA) e pili ana i ka pale ʻana e hana i kahi kumu hoʻohālike wānana pololei a paʻa hoʻi [8].
Ua loaʻa nā ʻikepili RNAseq maʻamau (FPKM) a me ka ʻikepili TCGA no ka maʻi kanesa pancreatic a me ka ʻikepili genotype tissue expression (GTEx) mai ka waihona ʻikepili UCSC XENA (https://xenabrowser.net/datapages/). Ua loaʻa nā faila GTF mai ka waihona ʻikepili Ensembl (http://asia.ensembl.org) a ua hoʻohana ʻia e unuhi i nā ʻikepili hōʻike lncRNA mai RNAseq. Ua hoʻoiho mākou i nā genes e pili ana i ka pale ʻana mai ka waihona ʻikepili ImmPort (http://www.immport.org) a ua ʻike i nā lncRNA e pili ana i ka pale ʻana (irlncRNAs) me ka hoʻohana ʻana i ka loiloi correlation (p <0.001, r > 0.4). Ka ʻike ʻana i nā irlncRNA i hōʻike ʻokoʻa ʻia (DEirlncRNAs) ma ke keʻa ʻana i nā irlncRNA a me nā lncRNA i hōʻike ʻokoʻa ʻia i loaʻa mai ka waihona ʻikepili GEPIA2 (http://gepia2.cancer-pku.cn/#index) ma ka cohort TCGA-PAAD (|logFC| > 1 a me FDR) <0.05).
Ua hōʻike mua ʻia kēia ʻano hana [8]. Ma ke ʻano kikoʻī, kūkulu mākou iā X e pani i ka lncRNA A a me lncRNA B i hui pū ʻia. Ke kiʻekiʻe aʻe ka waiwai hōʻike o lncRNA A ma mua o ka waiwai hōʻike o lncRNA B, ua wehewehe ʻia ʻo X he 1, inā ʻaʻole ua wehewehe ʻia ʻo X he 0. No laila, hiki iā mākou ke loaʻa kahi matrix o 0 a i ʻole - 1. Hōʻike ka axis vertical o ka matrix i kēlā me kēia laʻana, a hōʻike ka axis horizontal i kēlā me kēia hui DEirlncRNA me ka waiwai o 0 a i ʻole 1.
Ua hoʻohana ʻia ka loiloi regression univariate i ukali ʻia e ka regression Lasso e nānā i nā hui DEirlncRNA prognostic. Ua hoʻohana ka loiloi regression lasso i ka 10-fold cross-validation i hana hou ʻia he 1000 mau manawa (p <0.05), me 1000 mau stimuli random no kēlā me kēia holo. I ka wā i ʻoi aku ai ke alapine o kēlā me kēia hui DEirlncRNA ma mua o 100 mau manawa i 1000 mau pōʻaiapuni, ua koho ʻia nā hui DEirlncRNA e kūkulu i kahi kumu hoʻohālike pilikia prognostic. A laila ua hoʻohana mākou i ka piʻo AUC e ʻike i ka waiwai cutoff kūpono no ka hoʻokaʻawale ʻana i nā maʻi PAAD i nā hui kiʻekiʻe a me ka haʻahaʻa. Ua helu ʻia a hoʻolālā ʻia ka waiwai AUC o kēlā me kēia kumu hoʻohālike ma ke ʻano he piʻo. Inā hiki ka piʻo i kahi kiʻekiʻe loa e hōʻike ana i ka waiwai AUC kiʻekiʻe loa, ua pau ke kaʻina hana helu a ua manaʻo ʻia ke kumu hoʻohālike ʻo ia ka moho maikaʻi loa. Ua kūkulu ʻia nā kumu hoʻohālike piʻo ROC 1-, 3- a me 5 makahiki. Ua hoʻohana ʻia nā loiloi regression univariate a me multivariate e nānā i ka hana wānana kūʻokoʻa o ke kumu hoʻohālike pilikia prognostic.
E hoʻohana i ʻehiku mau mea hana e aʻo ai i nā helu komo ʻana o nā cell immune, me XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, a me CIBERSORT. Ua hoʻoiho ʻia nā ʻikepili komo ʻana o nā cell immune mai ka waihona ʻikepili TIMER2 (http://timer.comp-genomics.org/#tab-5817-3). Ua kālailai ʻia ka ʻokoʻa o ka ʻike o nā cell immune-infiltrating ma waena o nā hui kiʻekiʻe a me nā hui haʻahaʻa o ke kumu hoʻohālike i kūkulu ʻia me ka hoʻohana ʻana i ka hoʻāʻo Wilcoxon signed-rank, hōʻike ʻia nā hopena ma ka pakuhi square. Ua hana ʻia ka loiloi correlation Spearman e kālailai i ka pilina ma waena o nā waiwai helu pilikia a me nā cell immune-infiltrating. Hōʻike ʻia ka coefficient correlation hopena ma ke ʻano he lollipop. Ua hoʻonohonoho ʻia ka paepae koʻikoʻi ma p < 0.05. Ua hana ʻia ke kaʻina hana me ka hoʻohana ʻana i ka pūʻolo R 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 komo ʻana o nā cell immune, ua hana mākou i ka pūʻolo ggstatsplot a me ka violin plot visualization.
No ka loiloi ʻana i nā ʻano lapaʻau lapaʻau no ka maʻi ʻaʻai pancreatic, ua helu mākou i ka IC50 o nā lāʻau chemotherapy i hoʻohana pinepine ʻia i ka hui TCGA-PAAD. Ua hoʻohālikelike ʻia nā ʻokoʻa ma nā hapalua inhibitory concentrations (IC50) ma waena o nā hui kiʻekiʻe a me nā hui haʻahaʻa me ka hoʻohana ʻana i ka hoʻāʻo Wilcoxon signed-rank, a ua hōʻike ʻia nā hopena ma ke ʻano he boxplots i hana ʻia me ka hoʻohana ʻana iā pRRophetic a me ggplot2 ma R. Hoʻokō nā ʻano hana āpau i nā alakaʻi a me nā loina pili.
Ua hōʻike ʻia ke kaʻina hana o kā mākou noiʻi ma ke Kiʻi 1. Ma ka hoʻohana ʻana i ka loiloi pilina ma waena o nā lncRNA a me nā genes e pili ana i ka pale ʻana, ua koho mākou i 724 irlncRNA me p <0.01 a me r > 0.4. A laila ua kālailai mākou i nā lncRNA i hōʻike ʻokoʻa ʻia o GEPIA2 (Kiʻi 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 DEirlncRNA.
Ke kūkulu ʻana i nā kumu hoʻohālike pilikia wānana. (A) Ka palapala lua pele o nā lncRNA i hōʻike ʻokoʻa ʻia. (B) Ka hoʻolaha ʻana o nā coefficients lasso no 20 mau hui DEirlncRNA. (C) ʻOkoʻa likelihood hapa o ka hoʻolaha coefficient LASSO. (D) Ka palapala ululāʻau e hōʻike ana i ka loiloi regression univariate o 20 mau hui DEirlncRNA.
Ma hope mai, ua kūkulu mākou i kahi matrix 0 a i ʻole 1 ma ka hoʻopili ʻana i 223 DEirlncRNA. Ua ʻike ʻia he 13,687 mau hui DEirlncRNA. Ma hope o ka nānā ʻana o ka univariate a me ka lasso regression, ua hoʻāʻo hope ʻia he 20 mau hui DEirlncRNA e kūkulu i kahi kumu hoʻohālike pilikia prognostic (Kiʻi 2B-D). Ma muli o nā hopena o ka Lasso a me ka nānā ʻana o ka regression lehulehu, ua helu mākou i kahi helu pilikia no kēlā me kēia maʻi ma ka cohort TCGA-PAAD (Papa 1). Ma muli o nā hopena o ka nānā ʻana o ka lasso regression, ua helu mākou i kahi helu pilikia no kēlā me kēia maʻi ma ka cohort TCGA-PAAD. ʻO ka AUC o ka piʻo ROC he 0.905 no ka wānana kumu hoʻohālike pilikia 1 makahiki, 0.942 no ka wānana 2 makahiki, a me 0.966 no ka wānana 3 makahiki (Kiʻi 3A-B). Ua hoʻonohonoho mākou i kahi waiwai cutoff kūpono o 3.105, ua hoʻokaʻawale i nā maʻi cohort TCGA-PAAD i nā hui kiʻekiʻe a me ka haʻahaʻa, a ua hoʻolālā i nā hopena ola a me nā helu pilikia no kēlā me kēia maʻi (Kiʻi 3C-E). Ua hōʻike ka loiloi Kaplan-Meier ua haʻahaʻa loa ke ola ʻana o nā maʻi PAAD i ka hui pilikia kiʻekiʻe ma mua o nā maʻi i ka hui haʻahaʻa (p < 0.001) (Kiʻi 3F).
Ka pono o nā hiʻohiʻona pilikia prognostic. (A) ROC o ke kumu hoʻohālike pilikia prognostic. (B) Nā hiʻohiʻona pilikia prognostic ROC 1-, 2-, a me 3 makahiki. (C) ROC o ke kumu hoʻohālike pilikia prognostic. Hōʻike i ke kiko ʻoki kūpono. (DE) Ka hoʻolaha ʻana o ke kūlana ola (D) a me nā helu pilikia (E). (F) Ka loiloi Kaplan-Meier o nā maʻi PAAD ma nā hui kiʻekiʻe a me ka haʻahaʻa.
Ua loiloi hou mākou i nā ʻokoʻa o nā helu pilikia ma o nā ʻano lapaʻau. Hōʻike ka palapala kaha (Kiʻi 4A) i ka pilina holoʻokoʻa ma waena o nā ʻano lapaʻau a me nā helu pilikia. Ma ke ʻano kūikawā, ʻoi aku ka kiʻekiʻe o nā helu pilikia o nā maʻi ʻelemakule (Kiʻi 4B). Eia kekahi, ʻoi aku ka kiʻekiʻe o nā helu pilikia o nā maʻi me ke kahua II ma mua o nā maʻi me ke kahua I (Kiʻi 4C). E pili ana i ka pae tumor i nā maʻi PAAD, ʻoi aku ka kiʻekiʻe o nā helu pilikia o nā maʻi papa 3 ma mua o nā maʻi papa 1 a me 2 (Kiʻi 4D). Ua hana hou mākou i nā loiloi regression univariate a me multivariate a hōʻike i ka helu pilikia (p < 0.001) a me ka makahiki (p = 0.045) he mau mea prognostic kūʻokoʻa i nā maʻi me PAAD (Kiʻi 5A-B). Ua hōʻike ka piʻo ROC ua ʻoi aku ka maikaʻi o ka helu pilikia ma mua o nā ʻano lapaʻau ʻē aʻe i ka wānana ʻana i ke ola 1-, 2-, a me 3 makahiki o nā maʻi me PAAD (Kiʻi 5C-E).
Nā ʻano lapaʻau o nā kumu hoʻohālike pilikia prognostic. Hōʻike ka Histogram (A) i ka (B) makahiki, (C) kahua puʻupuʻu, (D) māka puʻupuʻu, helu pilikia, a me ke kāne o nā maʻi ma ka hui TCGA-PAAD. **p < 0.01
Ka loiloi wānana kūʻokoʻa o nā hiʻohiʻona pilikia prognostic. (AB) Nā loiloi regression Univariate (A) a me multivariate (B) o nā hiʻohiʻona pilikia prognostic a me nā ʻano lapaʻau. (CE) ROC 1-, 2-, a me 3-makahiki 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 ua pili pono ka helu pilikia i nā maʻi PAAD me nā pūnaewele CD8+ T a me nā pūnaewele NK (Kiʻi 6A), e hōʻike ana i ka hana pale i hoʻopau ʻia i ka hui pilikia kiʻekiʻe. Ua loiloi pū mākou i ka ʻokoʻa o ka infiltration cell immune ma waena o nā hui pilikia kiʻekiʻe a me nā hui pilikia haʻahaʻa a ua loaʻa nā hopena like (Kiʻi 7). Ua emi ka infiltration o nā pūnaewele CD8+ T a me nā pūnaewele NK i ka hui pilikia kiʻekiʻe. I nā makahiki i hala iho nei, ua hoʻohana nui ʻia nā mea hoʻopaʻa checkpoint immune (ICIs) i ka mālama ʻana i nā puʻupuʻu paʻa. Eia naʻe, ʻaʻole i holomua ka hoʻohana ʻana i nā ICI i ka maʻi ʻaʻai pancreatic. No laila, ua loiloi mākou i ka hōʻike ʻana o nā genes checkpoint immune i nā hui pilikia kiʻekiʻe a me nā hui pilikia haʻahaʻa. Ua ʻike mākou ua hoʻonui nui ʻia ʻo CTLA-4 a me CD161 (KLRB1) i ka hui pilikia haʻahaʻa (Kiʻi 6B-G), e hōʻike ana he maʻalahi paha nā maʻi PAAD i ka hui pilikia haʻahaʻa i ka ICI.
Ka loiloi pilina o ke kumu hoʻohālike pilikia prognostic a me ka infiltration cell immune. (A) Ka pilina ma waena o ke kumu hoʻohālike pilikia prognostic a me ka infiltration cell immune. (BG) Hōʻike i ka hōʻike ʻana o ka gene i nā hui pilikia kiʻekiʻe a me ka haʻahaʻa. (HK) Nā waiwai IC50 no nā lāʻau anticancer kikoʻī i nā hui pilikia kiʻekiʻe a me ka haʻahaʻa. *p < 0.05, **p < 0.01, ns = ʻaʻole koʻikoʻi
Ua loiloi hou mākou i ka pilina ma waena o nā helu pilikia a me nā mea hana chemotherapy maʻamau i ka hui TCGA-PAAD. Ua ʻimi mākou i nā lāʻau anticancer i hoʻohana pinepine ʻia i ka maʻi kanesa pancreatic a ua kālailai i nā ʻokoʻa i kā lākou mau waiwai IC50 ma waena o nā hui kiʻekiʻe a me nā hui haʻahaʻa. Ua hōʻike nā hopena ua ʻoi aku ka kiʻekiʻe o ka waiwai IC50 o AZD.2281 (olaparib) i ka hui kiʻekiʻe, e hōʻike ana he kūʻē paha nā maʻi PAAD i ka hui kiʻekiʻe i ka lāʻau AZD.2281 (Kiʻi 6H). Eia kekahi, ua haʻahaʻa nā waiwai IC50 o paclitaxel, sorafenib, a me erlotinib i ka hui kiʻekiʻe (Kiʻi 6I-K). Ua ʻike hou mākou i 34 mau lāʻau anticancer me nā waiwai IC50 kiʻekiʻe i ka hui kiʻekiʻe a me 34 mau lāʻau anticancer me nā waiwai IC50 haʻahaʻa i ka hui kiʻekiʻe (Papa 2).
ʻAʻole hiki ke hōʻole ʻia he nui nā lncRNA, mRNA, a me miRNA e noho nei a he kuleana 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 miRNA i ka wānana ʻana i ke ola holoʻokoʻa i kekahi mau ʻano maʻi kanesa. ʻOiaʻiʻo, ua hoʻokumu ʻia nā hiʻohiʻona pilikia prognostic he nui ma luna o nā lncRNA. No ka laʻana, ʻo Luo et al. Ua hōʻike nā haʻawina he kuleana koʻikoʻi ʻo LINC01094 i ka hoʻolaha ʻana o PC a me ka metastasis, a ʻo ka hōʻike kiʻekiʻe o LINC01094 e hōʻike ana i ka ola maikaʻi ʻole o nā maʻi maʻi kanesa pancreatic [16]. ʻO ke aʻo ʻana i hōʻike ʻia e Lin et al. Ua hōʻike nā haʻawina ʻo ka downregulation o lncRNA FLVCR1-AS1 e pili ana me ka prognosis maikaʻi ʻole i nā maʻi maʻi kanesa pancreatic [17]. Eia naʻe, ʻaʻole i kūkākūkā nui ʻia nā lncRNA e pili ana i ka pale ʻana e pili ana i ka wānana ʻana i ke ola holoʻokoʻa o nā maʻi kanesa. I kēia manawa, ua kālele ʻia ka nui o ka hana ma ke kūkulu ʻana i nā hiʻohiʻona pilikia prognostic e wānana i ke ola o nā maʻi kanesa a no laila e hoʻoponopono i nā ʻano lapaʻau [18, 19, 20]. Ke ulu nei ka ʻike ʻana i ke kuleana koʻikoʻi o nā infiltrates immune i ka hoʻomaka ʻana o ka maʻi kanesa, ka holomua, a me ka pane ʻana i nā lāʻau lapaʻau e like me ka chemotherapy. Ua hōʻoia nā haʻawina he nui he kuleana koʻikoʻi ko nā pūnaewele pale ʻōpū e komo ana i ka tumor i ka pane ʻana i ka chemotherapy cytotoxic [21, 22, 23]. He mea nui ka microenvironment pale ʻōpū i ke ola o nā maʻi tumor [24, 25]. Hoʻohana nui ʻia ka immunotherapy, ʻoiai ka ICI therapy, i ka mālama ʻana i nā tumors paʻa [26]. Hoʻohana nui ʻia nā genes e pili ana i ka immune e kūkulu i nā hiʻohiʻona pilikia prognostic. No ka laʻana, ʻo Su et al. Hoʻokumu ʻia ke kumu hoʻohālike pilikia prognostic e pili ana i ka immune ma nā genes protein-coding e wānana i ka prognosis o nā maʻi maʻi kanesa ovarian [27]. He kūpono hoʻi nā genes non-coding e like me lncRNAs no ke kūkulu ʻana i nā hiʻohiʻona pilikia prognostic [28, 29, 30]. Ua hoʻāʻo ʻo Luo et al i ʻehā mau lncRNA e pili ana i ka immune a kūkulu i kahi kumu hoʻohālike wānana no ka pilikia o ka maʻi kanesa cervical [31]. Khan et al. Ua ʻike ʻia he 32 mau transcripts i hōʻike ʻokoʻa ʻia, a ma muli o kēia, ua hoʻokumu ʻia kahi kumu hoʻohālike wānana me 5 mau transcripts koʻikoʻi, i manaʻo ʻia he mea hana i ʻōlelo nui ʻia no ka wānana ʻana i ka hōʻole koke ʻana o ka biopsy ma hope o ka hoʻoili ʻana o ka puʻupaʻa [32].
Hoʻokumu ʻia ka hapa nui o kēia mau kumu hoʻohālike ma nā pae hōʻike gene, ʻo ia hoʻi nā genes coding protein a i ʻole nā genes non-coding. Eia nō naʻe, hiki i ka gene like ke loaʻa nā waiwai hōʻike like ʻole i nā genomes like ʻole, nā ʻano ʻikepili a me nā maʻi like ʻole, e alakaʻi ana i nā kuhi paʻa ʻole i nā hiʻohiʻona wānana. Ma kēia haʻawina, ua kūkulu mākou i kahi kumu hoʻohālike kūpono me ʻelua mau pālua o nā lncRNA, kūʻokoʻa i nā waiwai hōʻike pololei.
Ma kēia haʻawina, ua ʻike mākou i ka irlncRNA no ka manawa mua ma o ka loiloi correlation me nā genes e pili ana i ka pale ʻana. Ua nānā mākou i 223 DEirlncRNAs ma o ka hybridization me nā lncRNAs i hōʻike ʻokoʻa ʻia. ʻO ka lua, ua kūkulu mākou i kahi matrix 0-a i ʻole-1 e pili ana i ke ʻano hoʻohui DEirlncRNA i paʻi ʻia [31]. A laila ua hana mākou i nā loiloi regression univariate a me lasso e ʻike i nā hui DEirlncRNA prognostic a kūkulu i kahi kumu hoʻohālike pilikia wānana. Ua kālailai hou mākou i ka pilina ma waena o nā helu pilikia a me nā ʻano lapaʻau i nā maʻi me PAAD. Ua ʻike mākou ʻo kā mākou kumu hoʻohālike pilikia prognostic, ma ke ʻano he kumu prognostic kūʻokoʻa i nā maʻi PAAD, hiki ke hoʻokaʻawale pono i nā maʻi kiʻekiʻe mai nā maʻi haʻahaʻa a me nā maʻi kiʻekiʻe mai nā maʻi haʻahaʻa. Eia kekahi, ʻo nā waiwai AUC o ke kaʻe ROC o ke kumu hoʻohālike pilikia 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 kānaka noiʻi ua ʻoi aku ka maʻalahi o nā maʻi me ka infiltration kiʻekiʻe o nā cell CD8+ T i ka mālama ʻana iā ICI [33]. ʻO ka hoʻonui ʻia ʻana o ka nui o nā cell cytotoxic, nā cell CD56 NK, nā cell NK a me nā cell CD8+ T i loko o ka microenvironment pale ʻana o ka tumor kekahi o nā kumu no ka hopena hoʻopau ʻana o ka tumor [34]. Ua hōʻike nā haʻawina mua ua pili nui nā pae kiʻekiʻe o ka tumor-infiltrating CD4(+) T a me CD8(+) T me ke ola lōʻihi [35]. ʻO ka infiltration cell CD8 T maikaʻi ʻole, ka ukana neoantigen haʻahaʻa, a me kahi microenvironment tumor immunosuppressive kiʻekiʻe e alakaʻi ai i ka nele o ka pane i ka lāʻau ICI [36]. Ua ʻike mākou ua pili maikaʻi ʻole ka helu pilikia me nā cell CD8+ T a me nā cell NK, e hōʻike ana ʻaʻole kūpono nā maʻi me nā helu pilikia kiʻekiʻe no ka mālama ʻana iā ICI a he prognosis ʻoi aku ka maikaʻi ʻole.
ʻO CD161 kahi māka o nā pūnaewele pepehi kanaka kūlohelohe (NK). Hoʻopili nā pūnaewele T i hoʻololi ʻia e CD8+CD161+ CAR i ka hoʻonui ʻana i ka pono antitumor in vivo i nā hiʻohiʻona xenograft adenocarcinoma ductal pancreatic HER2+ [37]. Hoʻopili nā mea hoʻopaʻa checkpoint immune i ka cytotoxic T lymphocyte associated protein 4 (CTLA-4) a me nā ala o ka protein make cell i hoʻonohonoho ʻia 1 (PD-1)/programmed cell death ligand 1 (PD-L1) a he nui ka hiki ke loaʻa i nā wahi he nui. ʻOi aku ka haʻahaʻa o ka hōʻike ʻana o CTLA-4 a me CD161 (KLRB1) i nā hui pilikia kiʻekiʻe, e hōʻike hou ana ʻaʻole kūpono nā maʻi me nā helu pilikia kiʻekiʻe no ka mālama ʻana iā ICI. [38]
No ka loaʻa ʻana o nā koho lapaʻau kūpono no nā poʻe maʻi kiʻekiʻe, ua kālailai mākou i nā lāʻau anticancer like ʻole a ua ʻike ʻia he kūpono paha ka paclitaxel, sorafenib, a me ka erlotinib, i hoʻohana nui ʻia i nā poʻe maʻi me PAAD, no nā poʻe maʻi kiʻekiʻe me PAAD. [33]. Ua ʻike ʻo Zhang et al e hiki i nā mutations i kekahi ala pane hōʻino DNA (DDR) ke alakaʻi i ka prognosis maikaʻi ʻole i nā poʻe maʻi maʻi prostate [39]. Ua hōʻike ka hoʻokolohua Pancreatic Cancer Olaparib Ongoing (POLO) i ka mālama ʻana me ka olaparib i hoʻolōʻihi i ke ola ʻole me ka holomua i hoʻohālikelike ʻia me ka placebo ma hope o ka chemotherapy platinum-based mua i nā poʻe maʻi me ka pancreatic ductal adenocarcinoma a me nā germline BRCA1/2 mutations [40]. Hāʻawi kēia i ka manaʻolana koʻikoʻi e hoʻomaikaʻi nui ʻia nā hopena lapaʻau i kēia hui liʻiliʻi o nā poʻe maʻi. Ma kēia haʻawina, ʻoi aku ka kiʻekiʻe o ka waiwai IC50 o AZD.2281 (olaparib) i ka hui kiʻekiʻe, e hōʻike ana he kūʻē paha nā poʻe maʻi PAAD i ka hui kiʻekiʻe i ka mālama ʻana me AZD.2281.
Hoʻopuka nā kumu hoʻohālike wānana ma kēia haʻawina i nā hopena wānana maikaʻi, akā ua hoʻokumu ʻia lākou ma nā wānana loiloi. Pehea e hōʻoia ai i kēia mau hopena me ka ʻikepili lapaʻau he nīnau koʻikoʻi. Ua lilo ka Endoscopic fine needle aspiration ultrasonography (EUS-FNA) i mea pono ʻole no ka ʻike ʻana i nā lesions pancreatic paʻa a me nā extrapancreatic me ka ʻike o 85% a me ka specificity o 98% [41]. ʻO ka hiki ʻana mai o nā nila biopsy nila maikaʻi EUS (EUS-FNB) e pili ana i nā pono i ʻike ʻia ma luna o FNA, e like me ka pololei diagnostic kiʻekiʻe, ka loaʻa ʻana o nā laʻana e mālama i ke ʻano histological, a pēlā e hana ai i nā ʻiʻo pale kino he mea koʻikoʻi no kekahi mau diagnoses. staining kūikawā [42]. Ua hōʻoia kahi loiloi ʻōnaehana o ka palapala e hōʻike ana nā nila FNB (ʻoi aku ka 22G) i ka pono kiʻekiʻe loa i ka ʻohi ʻana i nā ʻiʻo mai nā puʻupuʻu pancreatic [43]. Ma ke ʻano lapaʻau, he kakaikahi wale nō o nā maʻi i kūpono no ke ʻoki radical, a ʻo ka hapa nui o nā maʻi he mau puʻupuʻu inoperable i ka manawa o ka hōʻoia mua. Ma ka hana lapaʻau, he hapa liʻiliʻi wale nō o nā maʻi i kūpono no ke ʻoki radical no ka mea ʻo ka hapa nui o nā maʻi he mau puʻupuʻu inoperable i ka manawa o ka hōʻoia mua. Ma hope o ka hōʻoia ʻana o ka pathological e EUS-FNB a me nā ʻano hana ʻē aʻe, koho pinepine ʻia ka lāʻau lapaʻau maʻamau ʻole e like me ka chemotherapy. ʻO kā mākou papahana noiʻi ma hope aku, ʻo ia ka hoʻāʻo ʻana i ke kumu hoʻohālike prognostic o kēia haʻawina i nā cohorts ʻokiʻoki a me nā nonsurgical ma o kahi loiloi retrospective.
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Ka manawa hoʻouna: Sep-22-2023