Ciwon daji na pancreatic yana daya daga cikin ciwace-ciwacen daji mafi muni a duniya tare da rashin hangen nesa.Sabili da haka, ana buƙatar ingantaccen samfurin tsinkaya don gano marasa lafiya da ke cikin haɗarin cutar kansar pancreatic don daidaita jiyya da haɓaka hasashen waɗannan marasa lafiya.
Mun sami The Cancer Genome Atlas (TCGA) pancreatic adenocarcinoma (PAAD) bayanan RNAseq daga bayanan UCSC Xena, gano lncRNAs masu alaƙa da rigakafi (irlncRNAs) ta hanyar nazarin daidaitawa, kuma an gano bambance-bambance tsakanin TCGA da ƙwayoyin adenocarcinoma na pancreatic na yau da kullun.DEirlncRNA) daga TCGA da genotype tissue expression (GTEx) na nama na pancreatic.An yi ƙarin nazari na regression na univariate da lasso don gina ƙirar sa hannu.Sa'an nan kuma muka ƙididdige yankin da ke ƙarƙashin lanƙwasa kuma mun ƙaddara ƙimar yanke mafi kyaun don gano marasa lafiya tare da adenocarcinoma na pancreatic mai girma da ƙananan haɗari.Don kwatanta halaye na asibiti, shigar da ƙwayoyin cuta na rigakafi, microenvironment immunosuppressive, da juriya na chemotherapy a cikin marasa lafiya da ciwon daji na pancreatic mai girma da ƙananan haɗari.
Mun gano nau'i-nau'i na DEirlncRNA guda 20 kuma mun tattara marasa lafiya bisa ga mafi kyawun ƙimar yankewa.Mun nuna cewa samfurin sa hannu na mu yana da gagarumin aiki a cikin tsinkayar hasashen marasa lafiya tare da PAAD.AUC na ROC curve shine 0.905 don hasashen shekara 1, 0.942 don hasashen shekaru 2, da 0.966 don hasashen shekaru 3.Marasa lafiya masu haɗari suna da ƙananan ƙimar rayuwa da munanan halaye na asibiti.Mun kuma nuna cewa marasa lafiya masu haɗari suna da rigakafi kuma suna iya haɓaka juriya ga immunotherapy.Ƙimar magungunan maganin ciwon daji irin su paclitaxel, sorafenib, da erlotinib bisa ga kayan aikin ƙididdiga na iya zama masu dacewa ga marasa lafiya masu haɗari tare da PAAD.
Gabaɗaya, bincikenmu ya kafa sabon ƙirar haɗarin tsinkaya dangane da haɗin gwiwar irlncRNA, wanda ya nuna ƙimar ƙima a cikin marasa lafiya da ciwon daji na pancreatic.Samfurin haɗarinmu na tsinkaye na iya taimakawa bambance marasa lafiya tare da PAAD waɗanda suka dace da jiyya.
Ciwon daji na pancreatic cuta ce mai muni tare da ƙarancin rayuwa na shekaru biyar da babban matsayi.A lokacin ganewar asali, yawancin marasa lafiya sun riga sun shiga matakan ci gaba.A cikin mahallin cutar ta COVID-19, likitoci da ma'aikatan aikin jinya suna fuskantar babban matsin lamba lokacin da suke kula da marasa lafiya da ke fama da cutar sankara, kuma dangin marasa lafiya kuma suna fuskantar matsi da yawa yayin yanke shawarar jiyya [1, 2].Kodayake an sami babban ci gaba a cikin jiyya na DOADs, irin su neoadjuvant therapy, resection tiyata, radiation far, chemotherapy, niyya kwayoyin far, da rigakafi dubawa inhibitors (ICIs), kawai game da 9% na marasa lafiya tsira shekaru biyar bayan ganewar asali [3] ].], 4].Saboda farkon bayyanar cututtuka na adenocarcinoma na pancreatic ba su da kyau, yawanci ana bincikar marasa lafiya tare da metastases a matakin ci gaba [5].Don haka, ga majiyyaci da aka ba, cikakken jiyya na ɗaiɗaikun dole ne a auna fa'ida da rashin amfanin duk zaɓuɓɓukan magani, ba kawai don tsawaita rayuwa ba, har ma don haɓaka ingancin rayuwa [6].Sabili da haka, samfurin tsinkaya mai inganci ya zama dole don kimanta hasashen mai haƙuri daidai [7].Don haka, ana iya zaɓar magani mai dacewa don daidaita rayuwa da ingancin rayuwar marasa lafiya tare da PAAD.
Rashin hasashe na PAAD ya samo asali ne saboda juriya ga magungunan chemotherapy.A cikin 'yan shekarun nan, an yi amfani da masu hana rigakafin rigakafi a ko'ina a cikin maganin ciwace-ciwacen daji [8].Duk da haka, amfani da ICI a cikin ciwon daji na pancreatic ba shi da nasara [9].Sabili da haka, yana da mahimmanci don gano marasa lafiya waɗanda zasu iya amfana daga maganin ICI.
Dogon RNA mara coding (lncRNA) nau'in RNA ne mara coding tare da kwafi> 200 nucleotides.LncRNAs sun yaɗu kuma sun ƙunshi kusan 80% na rubutun ɗan adam [10].Babban aikin aikin ya nuna cewa samfuran tsinkaya na tushen lncRNA na iya yin hasashen hasashen mai haƙuri yadda ya kamata [11, 12].Misali, an gano lncRNAs 18 da ke da alaƙa da autophagy don samar da sa hannun tsinkaya a cikin ciwon nono [13].An yi amfani da wasu lncRNA guda shida masu alaƙa da rigakafi don kafa fasalin hasashen glioma [14].
A cikin ciwon daji na pancreatic, wasu nazarin sun kafa sa hannu na tushen lncRNA don tsinkayar hasashen mai haƙuri.An kafa sa hannu na 3-lncRNA a cikin adenocarcinoma na pancreatic tare da yanki a ƙarƙashin ROC curve (AUC) na 0.742 kawai da cikakken rayuwa (OS) na shekaru 3 [15].Bugu da ƙari, ƙimar maganganun lncRNA sun bambanta tsakanin nau'ikan kwayoyin halitta daban-daban, tsarin bayanai daban-daban, da marasa lafiya daban-daban, kuma aikin ƙirar tsinkaya ba shi da kwanciyar hankali.Don haka, muna amfani da algorithm ɗin ƙirar ƙira, haɗawa da maimaitawa, don samar da sa hannu na lncRNA (irlncRNA) masu alaƙa da rigakafi don ƙirƙirar ingantaccen samfurin tsinkaya [8].
An daidaita bayanan RNAseq (FPKM) da ciwon daji na pancreatic TCGA da genotype tissue expression (GTEx) daga bayanan UCSC XENA (https://xenabrowser.net/datapages/).An samo fayilolin GTF daga bayanan Ensembl (http://asia.ensembl.org) kuma an yi amfani da su don cire bayanan bayanan lncRNA daga RNAseq.Mun zazzage kwayoyin halittar da ke da alaƙa da rigakafi daga bayanan ImmPort (http://www.immport.org) kuma mun gano lncRNAs masu alaƙa da rigakafi (irlncRNAs) ta amfani da nazarin daidaitawa (p <0.001, r> 0.4).Bayyana irlncRNAs daban-daban (DEirlncRNAs) ta hanyar ketare irlncRNAs da kuma bayyana lncRNAs daban-daban da aka samo daga bayanan GEPIA2 (http://gepia2.cancer-pku.cn/#index) a cikin ƙungiyar TCGA-PAAD (|logFC|> 1 da FDR). ) <0.05).
An ba da rahoton wannan hanyar a baya [8].Musamman, muna gina X don maye gurbin lncRNA A da lncRNA B. Lokacin da ƙimar magana ta lncRNA A ta fi darajar magana ta lncRNA B, X an bayyana shi azaman 1, in ba haka ba X an bayyana shi azaman 0. Don haka, zamu iya samun. matrix na 0 ko - 1. Tsayin matrix na tsaye yana wakiltar kowane samfurin, kuma axis a kwance yana wakiltar kowane nau'i na DEirlncRNA tare da darajar 0 ko 1.
Ana amfani da nazarin koma bayan da bai bambanta da Lasso regression wanda aka yi amfani da shi don auna nau'ikan DEirlncRNA masu tsinkaya.Binciken lasso regression yayi amfani da 10-ninka tabbatarwa-giciye maimaita sau 1000 (p <0.05), tare da 1000 bazuwar motsa jiki a kowace gudu.Lokacin da mitar kowane nau'in DEirlncRNA ya wuce sau 100 a cikin zagayowar 1000, an zaɓi nau'ikan DEirlncRNA don gina ƙirar haɗarin tsinkaya.Daga nan mun yi amfani da madaidaicin AUC don nemo madaidaicin ƙimar yanke don rarraba marasa lafiyar PAAD zuwa ƙungiyoyi masu girma da ƙananan haɗari.An ƙididdige ƙimar AUC na kowane ƙirar kuma an ƙididdige shi azaman mai lankwasa.Idan madaidaicin ya kai matsayi mafi girma yana nuna matsakaicin darajar AUC, tsarin lissafin yana tsayawa kuma ana ɗaukar samfurin a matsayin ɗan takara mafi kyau.1-, 3- da 5-shekara ROC model an gina su.An yi amfani da nazarce-nazarcen koma-baya na bai-daya da nau'i-nau'i don bincika aikin tsinkaya mai zaman kansa na ƙirar haɗarin tsinkaya.
Yi amfani da kayan aiki guda bakwai don nazarin ƙimar kutsewar ƙwayoyin rigakafi, gami da XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, da CIBERSORT.An zazzage bayanan shigar da ƙwayoyin rigakafi daga ma'ajin TIMER2 (http://timer.comp-genomics.org/#tab-5817-3).Bambance-bambance a cikin abun ciki na ƙwayoyin cuta masu shiga cikin ƙwayoyin cuta tsakanin ƙungiyoyi masu girma da ƙananan haɗari na ƙirar da aka gina an yi amfani da su ta amfani da gwajin darajar Wilcoxon, an nuna sakamakon a cikin jadawali.An gudanar da nazarin haɗin gwiwar Spearman don nazarin alakar da ke tsakanin ƙimar ƙimar haɗari da ƙwayoyin cuta masu shiga ciki.Ana nuna sakamakon haɗin kai a matsayin lollipop.An saita ƙimar mahimmanci a p <0.05.Anyi aikin ta amfani da kunshin R ggplot2.Don bincika alakar da ke tsakanin samfurin da matakan maganganun kwayoyin halittar da ke da alaƙa da ƙimar kutsewar ƙwayoyin rigakafi, mun yi kunshin ggstatsplot da hangen nesa na violin.
Don kimanta tsarin kula da asibiti don ciwon daji na pancreatic, mun ƙididdige IC50 na magungunan chemotherapy da aka saba amfani da su a cikin ƙungiyar TCGA-PAAD.Bambance-bambance a cikin ƙananan ƙananan inhibitory (IC50) tsakanin ƙungiyoyi masu girma da ƙananan haɗari an kwatanta su ta hanyar amfani da gwajin sa hannu na Wilcoxon, kuma an nuna sakamakon a matsayin akwatunan da aka yi amfani da su ta hanyar amfani da pRrophetic da ggplot2 a cikin R. Duk hanyoyin sun dace da jagororin da ka'idoji masu dacewa.
Ana nuna aikin aikin binciken mu a cikin Hoto 1. Yin amfani da bincike na daidaituwa tsakanin lncRNAs da kwayoyin da ke da alaka da rigakafi, mun zaɓi 724 irlncRNAs tare da p <0.01 da r> 0.4.Mu na gaba mun bincika lncRNAs daban-daban na GEPIA2 (Hoto 2A).An bayyana jimlar 223 irlncRNAs daban-daban tsakanin adenocarcinoma na pancreatic da nama na pancreatic (|logFC|> 1, FDR <0.05), mai suna DEirlncRNAs.
Gina samfuran haɗarin tsinkaya.(A) Makircin volcano na lncRNAs daban-daban da aka bayyana.(B) Rarraba coefficients na lasso don nau'ikan DEirlncRNA guda 20.(C) Sassan yuwuwar bambance-bambancen rabon rabon LASSO.(D) Makircin daji yana nuna nazarin koma baya na nau'ikan DEirlncRNA guda 20.
Mu na gaba mun gina matrix 0 ko 1 ta hanyar haɗa 223 DEirlncRNAs.An gano jimlar nau'ikan 13,687 DEirlncRNA.Bayan nazarin koma baya na univariate da lasso, 20 DEirlncRNA nau'i-nau'i a ƙarshe an gwada su don gina ƙirar haɗarin tsinkaya (Hoto 2B-D).Dangane da sakamakon Lasso da bincike mai yawa na sake dawowa, mun ƙididdige ƙimar haɗari ga kowane mai haƙuri a cikin ƙungiyar TCGA-PAAD (Table 1).Dangane da sakamakon binciken lasso regression, mun ƙididdige ƙimar haɗari ga kowane mai haƙuri a cikin ƙungiyar TCGA-PAAD.AUC na ROC mai lankwasa shine 0.905 don tsinkayar ƙirar haɗari na shekara 1, 0.942 don tsinkayar 2-shekara, da 0.966 don tsinkayar 3-shekara (Hoto 3A-B).Mun saita mafi kyawun ƙimar yankewa na 3.105, mun tsara majinyatan ƙungiyar TCGA-PAAD zuwa ƙungiyoyi masu girma da ƙananan haɗari, kuma mun tsara sakamakon rayuwa da rarraba ƙimar haɗari ga kowane mai haƙuri (Hoto 3C-E).Binciken Kaplan-Meier ya nuna cewa rayuwar marasa lafiya na PAAD a cikin ƙungiyar masu haɗari sun kasance ƙasa da ƙasa fiye da na marasa lafiya a cikin ƙananan haɗari (p <0.001) (Hoto 3F).
Ingantattun samfuran haɗarin tsinkaya.(A) ROC na samfurin haɗarin haɗari.(B) 1-, 2-, da 3-shekara ROC haɗarin haɗari.(C) ROC na samfurin haɗarin haɗari.Yana nuna mafi kyawun wurin yanke yankewa.(DE) Rarraba matsayin rayuwa (D) da ƙimar haɗari (E).(F) Binciken Kaplan-Meier na marasa lafiya na PAAD a cikin ƙungiyoyi masu girma da ƙananan haɗari.
Mun kara tantance bambance-bambance a cikin ƙimar haɗari ta hanyar halayen asibiti.Makircin tsiri (Hoto 4A) yana nuna alaƙa gabaɗaya tsakanin halayen asibiti da ƙimar haɗari.Musamman ma, tsofaffin marasa lafiya suna da ƙimar haɗari mafi girma (Hoto 4B).Bugu da ƙari, marasa lafiya da mataki na II suna da haɗari mafi girma fiye da marasa lafiya da mataki na I (Hoto 4C).Game da ƙwayar ƙwayar cuta a cikin marasa lafiya na PAAD, marasa lafiya na 3 suna da haɗari mafi girma fiye da marasa lafiya na 1 da 2 (Hoto 4D).Mun ci gaba da yin nazari na univariate da multivariate regression kuma mun nuna cewa haɗarin haɗari (p <0.001) da shekaru (p = 0.045) sun kasance abubuwan haɓaka masu zaman kansu a cikin marasa lafiya tare da PAAD (Hoto 5A-B).Hanyar ROC ta nuna cewa haɗarin haɗari ya fi sauran halaye na asibiti a cikin tsinkayar 1-, 2-, da 3-shekara rayuwa na marasa lafiya tare da PAAD (Hoto 5C-E).
Halayen asibiti na samfuran haɗarin haɗari.Histogram (A) yana nuna (B) shekaru, (C) matakin ƙari, (D) ƙimar ƙari, ƙimar haɗari, da jinsi na marasa lafiya a cikin ƙungiyar TCGA-PAAD.**p <0.01
Binciken tsinkayar tsinkaya mai zaman kansa na samfuran haɗarin tsinkaya.(AB) Univariate (A) da multivariate (B) nazarin sake dubawa na ƙididdigar haɗarin haɗari da halayen asibiti.(CE) 1-, 2-, da 3-shekara ROC don ƙirar haɗarin haɗari da halayen asibiti
Sabili da haka, mun bincika dangantakar tsakanin lokaci da ƙimar haɗari.Mun gano cewa ƙimar haɗari a cikin marasa lafiya na PAAD an haɗa su da sel CD8 + T da ƙwayoyin NK (Hoto 6A), yana nuna aikin garkuwar jiki a cikin ƙungiyar masu haɗari.Mun kuma kimanta bambanci a cikin shigar da ƙwayoyin rigakafi tsakanin ƙungiyoyi masu girma da ƙananan haɗari kuma mun sami sakamako iri ɗaya (Figure 7).An sami ƙarancin kutsewar ƙwayoyin CD8+ T da ƙwayoyin NK a cikin ƙungiyar masu haɗari.A cikin 'yan shekarun nan, an yi amfani da masu hana rigakafin rigakafi (ICIs) a ko'ina don maganin ciwace-ciwacen ƙwayoyi.Duk da haka, amfani da ICI a cikin ciwon daji na pancreatic yana da wuya a yi nasara.Sabili da haka, mun tantance maganganun ƙwayoyin ƙwayoyin cuta na rigakafi a cikin ƙungiyoyi masu girma da ƙananan haɗari.Mun gano cewa CTLA-4 da CD161 (KLRB1) sun yi yawa a cikin rukunin ƙananan haɗari (Figure 6B-G), yana nuna cewa marasa lafiya na PAAD a cikin ƙananan haɗari na iya zama masu kula da ICI.
Binciken daidaitawa na samfurin haɗarin tsinkaya da shigar da ƙwayoyin rigakafi.(A) Daidaita tsakanin ƙirar haɗarin tsinkaya da kutsen ƙwayoyin rigakafi.(BG) Yana Nuna maganganun kwayoyin halitta a cikin ƙungiyoyi masu haɗari da ƙananan haɗari.(HK) ƙimar IC50 don takamaiman magungunan anticancer a cikin ƙungiyoyi masu haɗari da ƙananan haɗari.*p <0.05, **p <0.01, ns = ba mahimmanci ba
Mun kara tantance haɗin kai tsakanin maƙiyin haɗari da ma'aikatan chemotherapy na gama gari a cikin ƙungiyar TCGA-PAAD.Mun nemo magungunan rigakafin ciwon daji da aka saba amfani da su a cikin ciwon daji na pancreatic kuma mun bincika bambance-bambance a cikin ƙimar su IC50 tsakanin ƙungiyoyi masu girma da ƙananan haɗari.Sakamakon ya nuna cewa darajar IC50 na AZD.2281 (olaparib) ya kasance mafi girma a cikin rukuni mai haɗari, yana nuna cewa marasa lafiya na PAAD a cikin ƙungiyar masu haɗari na iya tsayayya da maganin AZD.2281 (Figure 6H).Bugu da ƙari, ƙimar IC50 na paclitaxel, sorafenib, da erlotinib sun kasance ƙananan a cikin rukuni mai haɗari (Figure 6I-K).Mun kara gano magungunan 34 anticancer tare da ƙimar IC50 mafi girma a cikin ƙungiyar masu haɗari da kuma magungunan 34 anticancer tare da ƙananan ƙimar IC50 a cikin ƙungiyar masu haɗari (Table 2).
Ba za a iya musun cewa lncRNAs, mRNAs, da miRNAs sun wanzu kuma suna taka muhimmiyar rawa a ci gaban kansa.Akwai kwararan shaidu da ke goyan bayan muhimmiyar rawar mRNA ko miRNA wajen tsinkayar rayuwa gabaɗaya a cikin nau'ikan ciwon daji da yawa.Babu shakka, yawancin nau'ikan haɗarin haɗari suma sun dogara ne akan lncRNAs.Alal misali, Luo et al.Nazarin ya nuna cewa LINC01094 yana taka muhimmiyar rawa a haɓakar PC da metastasis, kuma babban magana na LINC01094 yana nuna rashin lafiyar marasa lafiya na pancreatic ciwon daji [16].Binciken da Lin et al.Nazarin ya nuna cewa raguwar lncRNA FLVCR1-AS1 yana da alaƙa da rashin fahimta mara kyau a cikin marasa lafiya na pancreatic [17].Koyaya, lncRNAs masu alaƙa da rigakafi ba a ɗan tattauna su sosai dangane da tsinkayar rayuwar masu cutar kansa gabaɗaya.Kwanan nan, an mai da hankali kan babban adadin aiki don gina samfuran haɗarin haɗari don tsinkaya rayuwar marasa lafiya da ciwon daji kuma ta haka ne daidaita hanyoyin jiyya [18, 19, 20].Ana samun fahimtar mahimmancin rawar da ke tattare da garkuwar jiki a farkon cutar kansa, ci gaba, da kuma mayar da martani ga jiyya kamar chemotherapy.Yawancin karatu sun tabbatar da cewa ƙwayoyin rigakafi masu kamuwa da ƙwayar cuta suna taka muhimmiyar rawa wajen mayar da martani ga chemotherapy na cytotoxic [21, 22, 23].Ciwon ƙwayar cuta na rigakafi yana da muhimmiyar mahimmanci a cikin rayuwar marasa lafiya na ciwon daji [24, 25].Immunotherapy, musamman magungunan ICI, ana amfani dashi sosai a cikin maganin ciwace-ciwacen ƙwayoyi [26].Kwayoyin da ke da alaƙa da rigakafi ana amfani da su sosai don gina ƙirar haɗarin haɗari.Misali, Su et al.Samfurin haɗarin haɗari mai alaƙa da rigakafi ya dogara ne akan ƙwayoyin furotin-coding don hango hasashen hasashen marasa lafiya na ovarian [27].Kwayoyin da ba su da lambar kamar lncRNAs suma sun dace da gina samfuran haɗarin tsinkaya [28, 29, 30].Luo et al sun gwada lncRNA guda huɗu masu alaƙa da rigakafi kuma sun gina ƙirar tsinkaya don haɗarin kansar mahaifa [31].Khan et al.An gano jimlar 32 da aka bayyana daban-daban kwafi, kuma bisa ga wannan, an kafa samfurin tsinkaya tare da mahimman bayanan 5, wanda aka ba da shawarar azaman kayan aikin da aka ba da shawarar sosai don tsinkayar biopsy-tabbatar da ƙiyayya mai ƙarfi bayan dashen koda [32].
Yawancin waɗannan samfuran sun dogara ne akan matakan maganganun kwayoyin halitta, ko dai kwayoyin halittar sunadaran sunadaran ko kuma waɗanda ba sa coding.Koyaya, wannan nau'in kwayar halitta na iya samun ƙimar magana daban-daban a cikin nau'ikan genomes daban-daban, tsarin bayanai da kuma a cikin marasa lafiya daban-daban, wanda ke haifar da ƙididdige ƙididdiga a cikin samfuran tsinkaya.A cikin wannan binciken, mun gina ingantaccen tsari tare da nau'i-nau'i na lncRNA guda biyu, masu zaman kansu daga ainihin ƙimar magana.
A cikin wannan binciken, mun gano irlncRNA a karon farko ta hanyar nazarin alaƙa tare da kwayoyin da ke da alaƙa da rigakafi.Mun bincika 223 DEirlncRNAs ta hanyar haɓaka tare da bayyana lncRNAs daban-daban.Na biyu, mun gina matrix 0-ko-1 dangane da hanyar haɗin gwiwar DEirlncRNA da aka buga [31].Daga nan mun yi nazari na univariate da lasso regression don gano nau'i-nau'i na DEirlncRNA mai tsinkaya da gina ƙirar haɗarin tsinkaya.Mun kara nazarin haɗin gwiwa tsakanin ƙimar haɗari da halayen asibiti a cikin marasa lafiya tare da PAAD.Mun gano cewa samfurin haɗarinmu na haɓakawa, a matsayin wani abu mai zaman kanta a cikin marasa lafiya na PAAD, zai iya bambanta marasa lafiya masu daraja daga marasa lafiya marasa lafiya da marasa lafiya masu daraja daga marasa lafiya marasa lafiya.Bugu da ƙari, ƙimar AUC na madaidaicin ROC na ƙirar haɗarin haɗari sun kasance 0.905 don hasashen 1-shekara, 0.942 don hasashen 2-shekara, da 0.966 don hasashen 3-shekara.
Masu bincike sun ba da rahoton cewa marasa lafiya tare da mafi girma CD8 + T cell infiltration sun fi kula da maganin ICI [33].Haɓaka abun ciki na ƙwayoyin cytotoxic, ƙwayoyin CD56 NK, ƙwayoyin NK da CD8+ T a cikin ƙwayoyin ƙwayoyin cuta na ƙwayar cuta na iya zama ɗaya daga cikin dalilan da ke haifar da tasirin ƙwayar ƙwayar cuta [34].Nazarin da ya gabata ya nuna cewa manyan matakan CD4 (+) T da CD8 (+) T suna da alaƙa da tsayin rayuwa [35].Rashin ƙarancin CD8 T cell infiltration, ƙananan nauyin neoantigen, da ƙananan ƙwayoyin cuta na ƙwayoyin cuta suna haifar da rashin amsawa ga maganin ICI [36].Mun gano cewa haɗarin haɗari yana da alaƙa mara kyau tare da sel CD8 + T da ƙwayoyin NK, yana nuna cewa marasa lafiya da ke da babban haɗarin ƙila ba za su dace da jiyya na ICI ba kuma suna da tsinkaye mafi muni.
CD161 alama ce ta ƙwayoyin kisa ta halitta (NK).CD8+CD161+ CAR-canzawar ƙwayoyin T sel waɗanda aka haɓaka a cikin tasirin antitumor a cikin HER2+ pancreatic ductal adenocarcinoma xenograft model [37].Masu hana rigakafi na rigakafi sun yi amfani da cytotoxic T lymphocyte da ke hade da furotin 4 (CTLA-4) da furotin mutuwar kwayar halitta 1 (PD-1) / shirye-shiryen mutuwar kwayar cutar ligand 1 (PD-L1) kuma suna da babbar dama a wurare da yawa.Maganar CTLA-4 da CD161 (KLRB1) sun ragu a cikin ƙungiyoyi masu haɗari masu haɗari, suna kara nuna cewa marasa lafiya da ƙananan haɗari bazai cancanci samun magani na ICI ba.[38]
Don nemo zaɓuɓɓukan magani da suka dace da marasa lafiya masu haɗari, mun bincikar magungunan anticancer daban-daban kuma mun gano cewa paclitaxel, sorafenib, da erlotinib, waɗanda ake amfani da su sosai a cikin marasa lafiya tare da PAAD, na iya dacewa da marasa lafiya masu haɗari tare da PAAD.[33].Zhang et al ya gano cewa maye gurbi a cikin kowane hanyar lalacewar DNA (DDR) na iya haifar da rashin fahimta mara kyau a cikin marasa lafiya na prostate [39].Gwajin Ciwon daji na Pancreatic Olaparib na ci gaba (POLO) ya nuna cewa kulawar kulawa tare da olaparib ya tsawaita rayuwa marar ci gaba idan aka kwatanta da placebo bayan layin farko na platinum na chemotherapy a cikin marasa lafiya tare da pancreatic ductal adenocarcinoma da germline BRCA1/2 maye gurbi [40].Wannan yana ba da kyakkyawan fata cewa sakamakon jiyya zai inganta sosai a cikin wannan rukunin marasa lafiya.A cikin wannan binciken, ƙimar IC50 na AZD.2281 (olaparib) ya kasance mafi girma a cikin rukuni mai haɗari, yana nuna cewa marasa lafiya na PAAD a cikin ƙungiyar masu haɗari na iya tsayayya da jiyya tare da AZD.2281.
Samfuran tsinkaya a cikin wannan binciken suna samar da kyakkyawan sakamako na tsinkaya, amma sun dogara ne akan hasashen nazari.Yadda za a tabbatar da waɗannan sakamakon tare da bayanan asibiti tambaya ce mai mahimmanci.Endoscopic fine allura aspiration ultrasonography (EUS-FNA) ya zama wata hanya mai mahimmanci don bincikar raunuka masu ƙarfi da ƙari na pancreatic tare da azanci na 85% da takamaiman 98% [41].Zuwan EUS fine-needle biopsy (EUS-FNB) allura ya dogara ne akan fa'idodin da aka sani akan FNA, kamar ingantaccen bincike, samun samfuran da ke adana tsarin tarihi, don haka samar da nama na rigakafi wanda ke da mahimmanci ga wasu bincike.tabo ta musamman [42].Binciken da aka tsara na wallafe-wallafen ya tabbatar da cewa allurar FNB (musamman 22G) suna nuna mafi girman inganci a cikin girbi nama daga ƙwayar pancreatic [43].A asibiti, ƙananan marasa lafiya ne kawai suka cancanci yin tiyata mai tsattsauran ra'ayi, kuma yawancin marasa lafiya suna da ciwace-ciwace marasa aiki a lokacin ganewar asali.A cikin aikin asibiti, ƙananan ƙananan marasa lafiya ne kawai suka dace da tiyata mai tsattsauran ra'ayi saboda yawancin marasa lafiya suna da ciwace-ciwacen da ba za su iya aiki ba a lokacin ganewar asali.Bayan tabbatar da ilimin cututtuka ta hanyar EUS-FNB da sauran hanyoyin, ana zabar daidaitattun jiyya marasa aikin tiyata kamar chemotherapy.Shirin bincikenmu na gaba shine don gwada samfurin tsinkaya na wannan binciken a cikin ƙungiyoyin tiyata da marasa tiyata ta hanyar bincike na baya.
Gabaɗaya, bincikenmu ya kafa sabon ƙirar haɗarin tsinkaya dangane da haɗin gwiwar irlncRNA, wanda ya nuna ƙimar ƙima a cikin marasa lafiya da ciwon daji na pancreatic.Samfurin haɗarinmu na tsinkaye na iya taimakawa bambance marasa lafiya tare da PAAD waɗanda suka dace da jiyya.
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Lokacin aikawa: Satumba-22-2023