Ko te mate pukupuku repeure tetahi o ngā pukupuku tino whakamate o te ao, ā, he kino te matapae. Nō reira, me whai tauira matapae tika hei tautuhi i ngā tūroro e tino mōrearea ana ki te mate pukupuku repeure kia pai ai te maimoatanga me te whakapai ake i te matapae o ēnei tūroro.
I whiwhi mātou i ngā raraunga RNAseq o te Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) mai i te pātengi raraunga UCSC Xena, i tautuhia ngā lncRNA e pā ana ki te ārai mate (irlncRNA) mā te tātari hononga, ā, i tautuhia ngā rerekētanga i waenga i te TCGA me ngā kiko adenocarcinoma pancreatic noa. DEirlncRNA) mai i te TCGA me te whakaaturanga kiko iraira (GTEx) o te kiko pancreatic. I whakahaerehia ētahi atu tātaritanga univariate me te lasso regression hei hanga tauira waitohu matapae. Kātahi ka tatauhia e mātou te horahanga i raro i te pihi, ā, i whakatauhia te uara tapahi pai rawa atu mō te tautuhi i ngā tūroro me te adenocarcinoma pancreatic mōrearea nui me te iti. Hei whakataurite i ngā āhuatanga haumanu, te urunga pūtau ārai mate, te taiao moroiti ārai mate, me te ātete chemotherapy i roto i ngā tūroro me te mate pukupuku pancreatic mōrearea nui me te iti.
I tautuhia e mātou e 20 ngā takirua DEirlncRNA, ā, i whakarōpūhia ngā tūroro kia rite ki te uara tapahi tino pai. I whakaaturia e mātou he nui te mahi a tā mātou tauira waitohu matapae ki te matapae i te matapae o ngā tūroro me te PAAD. Ko te AUC o te pihi ROC he 0.905 mō te matapae 1-tau, 0.942 mō te matapae 2-tau, me te 0.966 mō te matapae 3-tau. He iti ake ngā reiti oranga o ngā tūroro mōrearea nui, ā, he kino ake ngā āhuatanga haumanu. I whakaaturia hoki e mātou he iti te pūnaha ārai mate o ngā tūroro mōrearea nui, ā, tera pea ka whanake he ātete ki te rongoā ārai mate. Ko te aromatawai i ngā rongoā ārai matepukupuku pēnei i te paclitaxel, sorafenib, me te erlotinib i runga i ngā taputapu matapae rorohiko he mea tika pea mō ngā tūroro mōrearea nui me te PAAD.
I te nuinga o te wā, i whakatūria e tā mātou rangahau tētahi tauira mōrearea matapae hou i runga i te irlncRNA takirua, i whakaatu i te uara matapae pai mō ngā tūroro mate pukupuku repeure. Tērā pea ka āwhina tā mātou tauira mōrearea matapae ki te wehewehe i ngā tūroro PAAD e tika ana mō te maimoatanga hauora.
He pukupuku kino te mate pukupuku repeure, he iti te ora mō ngā tau e rima, ā, he teitei te taumata. I te wā e tātaritatia ana, kua tae kē te nuinga o ngā tūroro ki ngā wāhanga kua tino matatau. I roto i te horopaki o te mate urutā COVID-19, kei raro i te pēhanga nui ngā tākuta me ngā nēhi i te wā e rongoā ana i ngā tūroro he mate pukupuku repeure, ā, he maha ngā pēhanga e pā ana ki ngā whānau o ngā tūroro i te wā e whakatau ana i ngā maimoatanga [1, 2]. Ahakoa kua nui ngā whanaketanga kua puta i roto i te maimoatanga o ngā DOAD, pērā i te rongoā neoadjuvant, te tango pokanga, te rongoā irahiko, te rongoā chemotherapy, te rongoā ngota arotahi, me ngā aukati ārai mate (ICI), tata ki te 9% noa iho o ngā tūroro e ora ana i ngā tau e rima i muri i te tātaritatanga [3]. ], 4]. Nā te mea he rerekē ngā tohu tōmua o te adenocarcinoma repeure, ka tātaritatia ngā tūroro he metastases i te wāhanga kua tino matatau [5]. Nō reira, mō tētahi tūroro, me paunatia e te maimoatanga whānui takitahi ngā painga me ngā ngoikoretanga o ngā kōwhiringa maimoatanga katoa, ehara i te mea hei whakaroa i te ora, engari hei whakapai ake i te kounga o te oranga [6]. Nō reira, me whai tauira matapae whai hua hei aromatawai tika i te matapae o te tūroro [7]. Nō reira, ka taea te whiriwhiri i te maimoatanga tika hei whakataurite i te oranga me te kounga o te oranga o ngā tūroro me te PAAD.
Ko te āhua kino o te PAAD i ahu mai i te ātete ki ngā rongoā chemotherapy. I ngā tau tata nei, kua whānuitia te whakamahinga o ngā aukati ārai mate hei rongoā i ngā pukupuku totoka [8]. Heoi, he onge te angitu o te whakamahinga o ngā ICI i roto i te mate pukupuku repe [9]. Nō reira, he mea nui kia tautuhia ngā tūroro ka whai hua pea mai i te rongoā ICI.
Ko te RNA roa kore-waehere (lncRNA) he momo RNA kore-waehere me ngā tuhinga neke atu i te 200 ngā nucleotide. He whānui ngā LncRNA, ā, tata ki te 80% o te tuhinga tangata [10]. He nui ngā mahi kua whakaatu ka taea e ngā tauira matapae e ahu mai ana i te lncRNA te matapae pai i te matapae o te tūroro [11, 12]. Hei tauira, 18 ngā lncRNA e pā ana ki te autophagy i tautuhia hei whakaputa i ngā waitohu matapae i roto i te mate pukupuku ū [13]. E ono atu ngā lncRNA e pā ana ki te ārai mate kua whakamahia hei whakatū i ngā āhuatanga matapae o te glioma [14].
I roto i te mate pukupuku repeure, kua whakatūria e ētahi rangahau he waitohu e hangai ana ki te lncRNA hei matapae i te matapae o te tūroro. I whakatūria he waitohu 3-lncRNA i roto i te adenocarcinoma repeure me te horahanga i raro i te pihi ROC (AUC) o te 0.742 anake me te oranga whānui (OS) o te 3 tau [15]. Hei tāpiri, he rerekē ngā uara whakaaturanga lncRNA i waenga i ngā ira rerekē, ngā whakatakotoranga raraunga rerekē, me ngā tūroro rerekē, ā, he koretake te mahi a te tauira matapae. Nō reira, ka whakamahia e mātou he raupapa tauira hou, te takirua me te whakahoutanga, hei whakaputa i ngā waitohu lncRNA (irlncRNA) e pā ana ki te ārai mate hei hanga i tētahi tauira matapae tika ake, pumau ake [8].
I tangohia mai ngā raraunga RNAseq kua whakaōritea (FPKM) me ngā raraunga TCGA mō te mate pukupuku repe taiaki haumanu me te whakaaturanga kiko iraira (GTEx) mai i te pātengi raraunga UCSC XENA (https://xenabrowser.net/datapages/). I tangohia mai ngā kōnae GTF mai i te pātengi raraunga Ensembl (http://asia.ensembl.org) ā, i whakamahia hei tango i ngā kōtaha whakaaturanga lncRNA mai i te RNAseq. I tangohia e mātou ngā ira e pā ana ki te ārai mate mai i te pātengi raraunga ImmPort (http://www.immport.org) ā, i tautuhia ngā lncRNA e pā ana ki te ārai mate (irlncRNA) mā te whakamahi i te tātaritanga hononga (p < 0.001, r > 0.4). Te tautuhi i ngā irlncRNA rerekē te whakaaturanga (DEirlncRNA) mā te whakawhiti i ngā irlncRNA me ngā lncRNA rerekē te whakaaturanga i tangohia mai i te pātengi raraunga GEPIA2 (http://gepia2.cancer-pku.cn/#index) i roto i te rōpū TCGA-PAAD (|logFC| > 1 me te FDR) <0.05).
Kua pūrongohia tēnei tikanga i mua [8]. Ina koa, ka hangaia e mātou a X hei whakakapi i te takirua lncRNA A me te lncRNA B. Ina teitei ake te uara whakapuakitanga o te lncRNA A i te uara whakapuakitanga o te lncRNA B, ka tautuhia a X hei 1, ki te kore ka tautuhia a X hei 0. Nō reira, ka taea e tātou te whiwhi i tētahi matihiko o te 0, – 1 rānei. Ko te tuaka poutū o te matihiko e tohu ana i ia tauira, ā, ko te tuaka whakapae e tohu ana i ia takirua DEirlncRNA me te uara o te 0, 1 rānei.
I whakamahia te tātaritanga whakatauira kotahi-taurangi, ā, i whai ake ko te whakatauira Lasso hei tirotiro i ngā takirua DEirlncRNA matapae. I whakamahia e te tātaritanga whakatauira lasso te whakamana whakawhiti-10-wā i whakahokia 1000 ngā wā (p < 0.05), me te 1000 whakaohooho matapōkere mō ia oma. I te wā i neke atu ai te auau o ia takirua DEirlncRNA i te 100 ngā wā i roto i te 1000 huringa, i tīpakohia ngā takirua DEirlncRNA hei hanga i tētahi tauira mōrearea matapae. I muri mai ka whakamahia e mātou te pihi AUC hei kimi i te uara tapahi pai rawa atu mō te whakarōpū i ngā tūroro PAAD ki ngā rōpū mōrearea teitei me te iti. I tatauhia hoki te uara AUC o ia tauira, ā, i tuhia hei pihi. Mena ka tae te pihi ki te pūwāhi teitei rawa e tohu ana i te uara AUC mōrahi, ka mutu te tukanga tatau, ā, ka kiia te tauira ko te kaitono pai rawa atu. I hangaia ngā tauira pihi ROC 1-, 3- me te 5-tau. I whakamahia ngā tātaritanga whakatauira kotahi-taurangi me te maha-taurangi hei tirotiro i te mahi matapae motuhake o te tauira mōrearea matapae.
Whakamahia ngā taputapu e whitu hei ako i ngā reiti urunga pūtau ārai mate, tae atu ki a XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, me CIBERSORT. I tangohia ngā raraunga urunga pūtau ārai mate mai i te pātengi raraunga TIMER2 (http://timer.comp-genomics.org/#tab-5817-3). I tātarihia te rerekētanga o te ihirangi o ngā pūtau urunga-ārai mate i waenga i ngā rōpū mōrearea-tiketike me ngā rōpū mōrearea-iti o te tauira i hangaia mā te whakamahi i te whakamātautau Wilcoxon signed-rank, ka whakaaturia ngā hua ki te kauwhata tapawhā. I whakahaerehia te tātari hononga Spearman hei tātari i te whanaungatanga i waenga i ngā uara kaute mōrearea me ngā pūtau urunga-ārai mate. Ka whakaaturia te tauwehenga hononga hua hei lollipop. I whakatakotoria te paepae hiranga ki te p < 0.05. I whakahaerehia te tukanga mā te whakamahi i te mōkihi R ggplot2. Hei tirotiro i te whanaungatanga i waenga i te tauira me ngā taumata whakaaturanga ira e pā ana ki te reiti urunga pūtau ārai mate, i whakahaerehia e mātou te mōkihi ggstatsplot me te whakaaturanga kauwhata violin.
Hei aromatawai i ngā tauira maimoatanga haumanu mō te mate pukupuku repeure, i tatauhia e mātou te IC50 o ngā rongoā chemotherapy e whakamahia whānuitia ana i roto i te rōpū TCGA-PAAD. I whakaritea ngā rerekētanga o te haurua o ngā kukū aukati (IC50) i waenga i ngā rōpū mōrearea nui me ngā rōpū mōrearea iti mā te whakamahi i te whakamātautau Wilcoxon signed-rank, ā, ka whakaaturia ngā hua hei pouaka kauwhata i hangaia mā te whakamahi i te pRRophetic me te ggplot2 i roto i te R. E tutuki ana ngā tikanga katoa i ngā aratohu me ngā paerewa e tika ana.
Kei te Pikitia 1 te rere o tā mātou rangahau. Mā te whakamahi i te tātari hononga i waenga i ngā lncRNA me ngā ira e pā ana ki te ārai mate, i tīpakohia e mātou he 724 irlncRNA me te p < 0.01 me te r > 0.4. I muri mai ka tātarihia e mātou ngā lncRNA rerekē te whakaaturanga o te GEPIA2 (Pikitia 2A). E 223 ngā irlncRNA katoa i rerekē te whakaaturanga i waenga i te adenocarcinoma pancreatic me te kiko pancreatic noa (|logFC| > 1, FDR < 0.05), ko ngā DEirlncRNA te ingoa.
Te hanga tauira mōrearea matapae. (A) Kauwhata puia o ngā lncRNA rerekē te whakaaturanga. (B) Te tohatoha o ngā tauwehenga lasso mō ngā takirua DEirlncRNA e 20. (C) Te rerekētanga tūponotanga ā-wāhanga o te tohatoha tauwehenga LASSO. (D) Kauwhata ngahere e whakaatu ana i te tātaritanga whakatauira kotahi o ngā takirua DEirlncRNA e 20.
I muri mai ka hangaia e mātou he matihiko 0, 1 rānei mā te hono i te 223 DEirlncRNA. I tautuhia katoatia he 13,687 ngā takirua DEirlncRNA. Whai muri i te tātaritanga univariate me te lasso regression, i whakamatautauria kia 20 ngā takirua DEirlncRNA hei hanga i tētahi tauira mōrearea matapae (Pikitia 2B-D). I runga i ngā hua o te tātaritanga Lasso me te maha regression, i tatauhia e mātou he kaute mōrearea mō ia tūroro i roto i te rōpū TCGA-PAAD (Ripanga 1). I runga i ngā hua o te tātaritanga lasso regression, i tatauhia e mātou he kaute mōrearea mō ia tūroro i roto i te rōpū TCGA-PAAD. Ko te AUC o te pihi ROC he 0.905 mō te matapae tauira mōrearea 1-tau, 0.942 mō te matapae 2-tau, me te 0.966 mō te matapae 3-tau (Pikitia 3A-B). I whakatakotoria e mātou he uara tapahi tino pai o te 3.105, i wehewehea ngā tūroro o te rōpū TCGA-PAAD ki ngā rōpū mōrearea-tiketike me ngā rōpū mōrearea-iti, ā, i tuhia ngā putanga oranga me ngā tohatoha kaute mōrearea mō ia tūroro (Pikitia 3C-E). I whakaatuhia e te tātaritanga Kaplan-Meier he iti ake te oranga o ngā tūroro PAAD i roto i te rōpū mōrearea-tiketike i tērā o ngā tūroro i roto i te rōpū mōrearea-iti (p < 0.001) (Pikitia 3F).
Te whai mana o ngā tauira mōrearea matapae. (A) ROC o te tauira mōrearea matapae. (B) Ngā tauira mōrearea matapae ROC 1-, 2-, me te 3-tau. (C) ROC o te tauira mōrearea matapae. E whakaatu ana i te pūwāhi tapahi pai rawa atu. (DE) Te tohatoha o te tūnga oranga (D) me ngā kaute mōrearea (E). (F) Te tātaritanga Kaplan-Meier o ngā tūroro PAAD i roto i ngā rōpū mōrearea teitei me te iti.
I arotakehia anō e mātou ngā rerekētanga o ngā kaute mōrearea mā ngā āhuatanga haumanu. E whakaatu ana te kauwhata rīpene (Pikitia 4A) i te whanaungatanga whānui i waenga i ngā āhuatanga haumanu me ngā kaute mōrearea. Ina koa, he nui ake ngā kaute mōrearea o ngā tūroro pakeke ake (Pikitia 4B). Hei tāpiri, he nui ake ngā kaute mōrearea o ngā tūroro me te wāhanga II i ngā tūroro me te wāhanga I (Pikitia 4C). Mō te taumata pukupuku i roto i ngā tūroro PAAD, he nui ake ngā kaute mōrearea o ngā tūroro taumata 3 i ngā tūroro taumata 1 me te 2 (Pikitia 4D). I whakahaerehia anō e mātou ngā tātaritanga whakatautau kotahi me te maha, ā, i whakaaturia ko te kaute mōrearea (p < 0.001) me te tau (p = 0.045) he āhuatanga matapae motuhake i roto i ngā tūroro me te PAAD (Pikitia 5A-B). I whakaatuhia e te pihi ROC he pai ake te kaute mōrearea i ētahi atu āhuatanga haumanu i roto i te matapae i te oranga 1-, 2-, me te 3-tau o ngā tūroro me te PAAD (Pikitia 5C-E).
Ngā āhuatanga haumanu o ngā tauira mōrearea matapae. E whakaatu ana te kauwhata (A) i te (B) tau, (C) wāhanga pukupuku, (D) taumata pukupuku, kaute mōrearea, me te ira tangata o ngā tūroro i roto i te rōpū TCGA-PAAD. **p < 0.01
Tātari matapae motuhake o ngā tauira mōrearea matapae. (AB) Ngā tātari whakatauira kotahi-taurangi (A) me te maha-taurangi (B) o ngā tauira mōrearea matapae me ngā āhuatanga haumanu. (CE) ROC 1-, 2-, me te 3-tau mō ngā tauira mōrearea matapae me ngā āhuatanga haumanu
Nō reira, i tirotirohia e mātou te whanaungatanga i waenga i te wā me ngā kaute mōrearea. I kitea e mātou he hononga whakahuri te kaute mōrearea i roto i ngā tūroro PAAD ki ngā pūtau CD8+ T me ngā pūtau NK (Pikitia 6A), e tohu ana i te ngoikore o te mahi ārai mate i roto i te rōpū mōrearea nui. I aromatawaihia hoki e mātou te rerekētanga o te urunga o ngā pūtau ārai mate i waenga i ngā rōpū mōrearea nui me ngā rōpū mōrearea iti, ā, i kitea ngā hua ōrite (Pikitia 7). He iti ake te urunga o ngā pūtau CD8+ T me ngā pūtau NK i roto i te rōpū mōrearea nui. I ngā tau tata nei, kua whānuitia te whakamahinga o ngā aukati ārai mate (ICI) hei rongoā i ngā pukupuku totoka. Heoi, he onge te angitu o te whakamahinga o ngā ICI i roto i te mate pukupuku repeure. Nō reira, i aromatawaihia e mātou te whakaaturanga o ngā ira ārai mate i roto i ngā rōpū mōrearea nui me ngā rōpū mōrearea iti. I kitea e mātou he nui rawa te whakaaturanga o CTLA-4 me CD161 (KLRB1) i roto i te rōpū mōrearea iti (Pikitia 6B-G), e tohu ana ko ngā tūroro PAAD i roto i te rōpū mōrearea iti ka tairongo pea ki te ICI.
Tātari hononga o te tauira mōrearea matapae me te urunga pūtau ārai mate. (A) Hononga i waenga i te tauira mōrearea matapae me te urunga pūtau ārai mate. (BG) E tohu ana i te whakaaturanga ira i roto i ngā rōpū mōrearea teitei me te iti. (HK) Ngā uara IC50 mō ngā rongoā ārai matepukupuku motuhake i roto i ngā rōpū mōrearea teitei me te iti. *p < 0.05, **p < 0.01, ns = kāore i te hiranga
I arotakehia anō e mātou te hononga i waenga i ngā kaute mōrearea me ngā kaihoko chemotherapy noa i roto i te rōpū TCGA-PAAD. I rapua e mātou ngā rongoā ārai matepukupuku e whakamahia whānuitia ana i roto i te matepukupuku repeure, ā, i tātarihia ngā rerekētanga o ō rātou uara IC50 i waenga i ngā rōpū mōrearea teitei me ngā rōpū mōrearea iti. I whakaatuhia e ngā hua he teitei ake te uara IC50 o AZD.2281 (olaparib) i roto i te rōpū mōrearea teitei, e tohu ana ko ngā tūroro PAAD i roto i te rōpū mōrearea teitei ka ātete pea ki te maimoatanga AZD.2281 (Pikitia 6H). Hei tāpiri, he iti ake ngā uara IC50 o paclitaxel, sorafenib, me te erlotinib i roto i te rōpū mōrearea teitei (Pikitia 6I-K). I tautuhia anō e mātou e 34 ngā rongoā ārai matepukupuku me ngā uara IC50 teitei ake i roto i te rōpū mōrearea teitei me te 34 ngā rongoā ārai matepukupuku me ngā uara IC50 iti ake i roto i te rōpū mōrearea teitei (Ripanga 2).
Kāore e taea te whakakorekore he whānuitia te noho o ngā lncRNA, ngā mRNA, me ngā miRNA, ā, he mea nui tā rātou mahi ki te whanaketanga o te mate pukupuku. He nui ngā taunakitanga e tautoko ana i te mahi nui a te mRNA, arā, te miRNA, ki te matapae i te oranga whānui i roto i ētahi momo mate pukupuku. Kāore e kore, he maha ngā tauira mōrearea matapae e ahu mai ana i ngā lncRNA. Hei tauira, kua whakaatuhia e Luo et al. he mahi nui tā LINC01094 ki te horapa me te horapa o te PC, ā, ko te nui o te whakaaturanga o LINC01094 e tohu ana i te oranga ngoikore o ngā tūroro mate pukupuku repe [16]. Kua whakaatuhia e te rangahau i tukuna e Lin et al. ko te whakahekenga o te lncRNA FLVCR1-AS1 e pā ana ki te oranga kino i roto i ngā tūroro mate pukupuku repe [17]. Heoi, he iti ake te kōrero mō ngā lncRNA e pā ana ki te ārai mate mō te matapae i te oranga whānui o ngā tūroro mate pukupuku. Nō nā tata nei, he nui ngā mahi kua arotahi ki te hanga tauira mōrearea matapae hei matapae i te oranga o ngā tūroro mate pukupuku, ā, mā reira ka whakatikatika i ngā tikanga maimoatanga [18, 19, 20]. Kei te piki haere te mōhio ki te mahi nui a ngā urutomo ārai mate ki te tīmatanga, te haere whakamua, me te urupare ki ngā maimoatanga pēnei i te chemotherapy. He maha ngā rangahau kua whakaū he mahi nui tā ngā pūtau ārai mate e uru ana ki te pukupuku i roto i te urupare ki te chemotherapy cytotoxic [21, 22, 23]. He mea nui te taiao ārai mate pukupuku ki te oranga o ngā tūroro pukupuku [24, 25]. He whānuitia te whakamahinga o te immunotherapy, inā koa te ICI therapy, hei rongoā i ngā pukupuku totoka [26]. He whānuitia te whakamahinga o ngā ira e pā ana ki te ārai mate hei hanga tauira mōrearea matapae. Hei tauira, ko Su et al. Ko te tauira mōrearea matapae e pā ana ki te ārai mate e ahu mai ana i ngā ira e whakakōrero ana i te pūmua hei matapae i te matapae o ngā tūroro mate pukupuku ovarian [27]. He pai hoki ngā ira kore-whakakōrero pēnei i ngā lncRNA mō te hanga tauira mōrearea matapae [28, 29, 30]. I whakamātauhia e Luo et al e whā ngā lncRNA e pā ana ki te ārai mate, ā, i hangaia he tauira matapae mō te mōrearea mate pukupuku waha kōpū [31]. I tautuhia e Khan et al. E 32 ngā tuhinga rerekē te whakaaturanga katoa, ā, i runga i tēnei, i whakatūria he tauira matapae me te 5 ngā tuhinga nui, i whakaarohia hei taputapu tino taunakitia mō te matapae i te whakakorenga ohorere kua whakamātauhia e te koiora i muri i te whakawhitinga whatukuhu [32].
Ko te nuinga o ēnei tauira e ahu mai ana i ngā taumata whakapuakanga ira, arā, ngā ira e whakakōwae ana i te pūmua, ngā ira kāore rānei e whakakōwae ana. Heoi anō, ka rerekē pea ngā uara whakapuakanga o te ira kotahi i roto i ngā ira rerekē, ngā whakatakotoranga raraunga me ngā tūroro rerekē, ā, ka hua ake he whakatau tata koretake i roto i ngā tauira matapae. I roto i tēnei rangahau, i hangaia e mātou he tauira whaitake me ngā takirua lncRNA e rua, kāore e pā ki ngā uara whakapuakanga tuturu.
I roto i tēnei rangahau, i tautuhia e mātou te irlncRNA mō te wā tuatahi mā te tātari hononga me ngā ira e pā ana ki te ārai mate. I tirotirohia e mātou te 223 DEirlncRNA mā te whakaranu me ngā lncRNA rerekē te whakaaturanga. Tuarua, i hangaia e mātou he matihiko 0-ranei-1 i runga i te tikanga takirua DEirlncRNA kua whakaputaina [31]. I muri mai ka whakahaerehia e mātou he tātaritanga univariate me te lasso regression hei tautuhi i ngā takirua DEirlncRNA matapae me te hanga i tētahi tauira mōrearea matapae. I tātarihia anō e mātou te hononga i waenga i ngā kaute mōrearea me ngā āhuatanga haumanu i roto i ngā tūroro me te PAAD. I kitea e mātou ko tā mātou tauira mōrearea matapae, hei āhuatanga matapae motuhake i roto i ngā tūroro PAAD, ka taea te wehewehe i ngā tūroro taumata teitei mai i ngā tūroro taumata iti me ngā tūroro taumata teitei mai i ngā tūroro taumata iti. Hei tāpiri, ko ngā uara AUC o te pihi ROC o te tauira mōrearea matapae he 0.905 mō te matapae 1-tau, 0.942 mō te matapae 2-tau, me te 0.966 mō te matapae 3-tau.
I rīpoatahia e ngā kairangahau he nui ake te aro o ngā tūroro he nui ake te urunga o ngā pūtau CD8+ T ki roto i te tinana mate pukupuku [33]. Ko te pikinga ake o ngā pūtau cytotoxic, ngā pūtau CD56 NK, ngā pūtau NK me ngā pūtau CD8+ T i roto i te taiao ārai mate pukupuku tētahi o ngā take mō te pānga pehi pukupuku [34]. I whakaatuhia e ngā rangahau o mua he nui ake te hononga o ngā taumata teitei o te CD4(+) T me te CD8(+) T e uru ana ki te pukupuku ki te roa o te oranga [35]. Ko te ngoikore o te urunga o ngā pūtau CD8 T, te iti o te kawenga neoantigen, me te taiao ārai mate pukupuku tino pehi i te ārai mate ka arahi ki te korenga o te urupare ki te rongoā ICI [36]. I kitea e mātou he hononga kino te kaute mōrearea ki ngā pūtau CD8+ T me ngā pūtau NK, e tohu ana ko ngā tūroro he nui ngā kaute mōrearea kāore pea e tika mō te maimoatanga ICI, ā, he kino ake te matapae.
Ko te CD161 he tohu mō ngā pūtau kaikōhuru taiao (NK). Ko ngā pūtau T CD8+CD161+ CAR-transduced e whakatairanga ana i te whai huatanga antitumor in vivo i roto i ngā tauira xenograft adenocarcinoma ductal pancreatic HER2+ [37]. Ko ngā aukati tirotiro ārai mate e aro ana ki te pūmua lymphocyte cytotoxic T 4 (CTLA-4) me te pūmua mate pūtau kua whakaritea 1 (PD-1)/ligant mate pūtau kua whakaritea 1 (PD-L1) ā, he nui te kaha ki ngā wāhi maha. He iti ake te whakaaturanga o te CTLA-4 me te CD161 (KLRB1) i roto i ngā rōpū mōrearea nui, e tohu ana anō kāore pea ngā tūroro he nui ngā kaute mōrearea e tika ana mō te maimoatanga ICI. [38]
Hei kimi i ngā kōwhiringa maimoatanga e tika ana mō ngā tūroro mōrearea nui, i tātarihia e mātou ngā momo rongoā ārai matepukupuku, ā, i kitea ko te paclitaxel, sorafenib, me te erlotinib, e whakamahia whānuitia ana i roto i ngā tūroro PAAD, he pai pea mō ngā tūroro mōrearea nui me te PAAD. [33]. I kitea e Zhang et al ko ngā whakarerekētanga i roto i tētahi ara urupare kino DNA (DDR) ka arahi ki te matapae kino i roto i ngā tūroro matepukupuku prostate [39]. I whakaatuhia e te whakamātautau Pancreatic Cancer Olaparib Ongoing (POLO) ko te maimoatanga pupuri me te olaparib i roa ake te ora kore-haere whakamua i whakaritea ki te placebo i muri i te chemotherapy e hangai ana ki te platinum raina tuatahi i roto i ngā tūroro me te adenocarcinoma ductal pancreatic me ngā whakarerekētanga germline BRCA1/2 [40]. Ka whakaratohia e tēnei he tumanako nui ka pai ake ngā putanga maimoatanga i roto i tēnei rōpū iti o ngā tūroro. I roto i tēnei rangahau, ko te uara IC50 o AZD.2281 (olaparib) he teitei ake i roto i te rōpū mōrearea nui, e tohu ana ko ngā tūroro PAAD i roto i te rōpū mōrearea nui ka ātete pea ki te maimoatanga me te AZD.2281.
He pai ngā hua matapae o ngā tauira matapae i roto i tēnei rangahau, engari e ahu mai ana i ngā matapae tātari. He pātai nui te pehea e whakaū ai i ēnei hua me ngā raraunga haumanu. Kua noho te ultrasonography ngongo ngira pai endoscopic (EUS-FNA) hei tikanga tino nui mō te tautuhi i ngā whara pancreatic totoka me te extrapancreatic me te aro o te 85% me te motuhake o te 98% [41]. Ko te taenga mai o ngā ngira koiora ngira pai EUS (EUS-FNB) e ahu mai ana i ngā painga kua kitea i runga i te FNA, pēnei i te tika o te taatai, te whiwhi tauira e tiaki ana i te hanganga histological, ā, nā reira ka puta he kiko ārai mate he mea nui mō ētahi taatai. he tae motuhake [42]. I whakaūhia e te arotake pūnaha o ngā tuhinga ko ngā ngira FNB (ina koa ko te 22G) e whakaatu ana i te tino whai huatanga ki te hauhake kiko mai i ngā puranga pancreatic [43]. I te taha haumanu, he iti noa iho ngā tūroro e tika ana mō te pokanga radical, ā, he maha ngā tūroro he pukupuku kāore e taea te mahi i te wā o te taatai tuatahi. I roto i te mahi haumanu, he iti noa iho te ōwehenga o ngā tūroro e tika ana mō te pokanga radical nā te mea he maha ngā tūroro he pukupuku kāore e taea te mahi i te wā o te taatai tuatahi. Whai muri i te whakaūnga o te mate mā te EUS-FNB me ētahi atu tikanga, ka whiriwhiria te maimoatanga paerewa kore-pokanga pērā i te chemotherapy. Ko tā mātou kaupapa rangahau e whai ake nei ko te whakamātautau i te tauira matapae o tēnei rangahau i roto i ngā rōpū pokanga me ngā rōpū kore-pokanga mā te tātari whakamuri.
I te nuinga o te wā, i whakatūria e tā mātou rangahau tētahi tauira mōrearea matapae hou i runga i te irlncRNA takirua, i whakaatu i te uara matapae pai mō ngā tūroro mate pukupuku repeure. Tērā pea ka āwhina tā mātou tauira mōrearea matapae ki te wehewehe i ngā tūroro PAAD e tika ana mō te maimoatanga hauora.
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Wā tuku: Hepetema-22-2023