Ciwon daji na pancreas yana ɗaya daga cikin ciwace-ciwacen da suka fi kisa a duniya, waɗanda ba su da kyakkyawan hasashen yadda za a yi hakan. Saboda haka, ana buƙatar ingantaccen tsarin hasashen don gano marasa lafiya da ke cikin haɗarin kamuwa da ciwon daji na pancreas don daidaita magani da inganta hasashen waɗannan marasa lafiya.
Mun sami bayanan RNAseq na The Cancer Genome Atlas (TCGA) na pancreas adenocarcinoma (PAAD) daga bayanan UCSC Xena, mun gano lncRNAs masu alaƙa da garkuwar jiki (irlncRNAs) ta hanyar nazarin alaƙa, kuma mun gano bambance-bambance tsakanin TCGA da kyallen adenocarcinoma na pancreas na yau da kullun. DEirlncRNA) daga TCGA da bayyanar ƙwayoyin halittar jini (GTex) na ƙwayar pancreas. An yi ƙarin nazarin univariate da lasso regression don gina samfuran sa hannu na hasashen yanayi. Sannan muka ƙididdige yankin da ke ƙarƙashin lanƙwasa kuma muka ƙayyade mafi kyawun ƙimar yankewa don gano marasa lafiya da adenocarcinoma na pancreas mai girma da ƙasa da haɗari. Don kwatanta halayen asibiti, shigar ƙwayoyin rigakafi, yanayin ƙwayoyin rigakafi, da juriya ga chemotherapy a cikin marasa lafiya da ke da ciwon daji na pancreas mai girma da ƙasa da haɗari.
Mun gano nau'ikan DEirlncRNA guda 20 da kuma marasa lafiya da aka haɗa bisa ga ƙimar yankewa mafi kyau. Mun nuna cewa samfurin sa hannun hasashenmu yana da babban aiki wajen hasashen hasashen marasa lafiya da ke fama da PAAD. AUC na lanƙwasa na ROC shine 0.905 don hasashen shekara 1, 0.942 don hasashen shekaru 2, da 0.966 don hasashen shekaru 3. Marasa lafiya masu haɗarin gaske suna da ƙarancin adadin rayuwa da mummunan halayen asibiti. Mun kuma nuna cewa marasa lafiya masu haɗarin gaske suna da ƙarancin rigakafi kuma suna iya haɓaka juriya ga maganin rigakafi. Kimanta magungunan hana ciwon daji kamar paclitaxel, sorafenib, da erlotinib bisa ga kayan aikin hasashen lissafi na iya dacewa da marasa lafiya masu haɗarin gaske tare da PAAD.
Gabaɗaya, bincikenmu ya kafa sabon samfurin haɗarin hasashen bisa ga haɗin irlncRNA, wanda ya nuna ƙimar hasashen hasashen ga marasa lafiya da ke fama da ciwon daji na pancreas. Tsarin haɗarin hasashenmu na iya taimakawa wajen bambance marasa lafiya da ke fama da PAAD waɗanda suka dace da maganin likita.
Ciwon daji na pancreas wani mummunan ƙari ne mai ƙarancin shekaru biyar na rayuwa da kuma babban matakin rayuwa. A lokacin da aka gano cutar, yawancin marasa lafiya sun riga sun shiga matakai na gaba. A cikin yanayin annobar COVID-19, likitoci da ma'aikatan jinya suna fuskantar matsin lamba mai yawa lokacin da suke kula da marasa lafiya da ke fama da ciwon daji na pancreas, kuma iyalan marasa lafiya suna fuskantar matsin lamba da yawa yayin yanke shawara game da magani [1, 2]. Duk da cewa an sami ci gaba mai yawa a cikin maganin DOADs, kamar maganin neoadjuvant, tiyatar tiyata, maganin radiation, chemotherapy, maganin kwayoyin halitta da aka yi niyya, da masu hana garkuwar jiki (ICIs), kusan kashi 9% ne kawai na marasa lafiya ke rayuwa shekaru biyar bayan ganewar asali [3]. ], 4]. Saboda alamun farko na adenocarcinoma na pancreas ba su da alaƙa, yawanci ana gano marasa lafiya da metastases a wani mataki na gaba [5]. Saboda haka, ga wani majiyyaci, cikakken magani na musamman dole ne ya auna fa'idodi da rashin amfanin duk zaɓuɓɓukan magani, ba wai kawai don tsawaita rayuwa ba, har ma don inganta ingancin rayuwa [6]. Saboda haka, samfurin hasashen inganci ya zama dole don tantance hasashen majiyyaci daidai [7]. Saboda haka, ana iya zaɓar magani mai dacewa don daidaita rayuwa da ingancin rayuwar marasa lafiya da ke fama da PAAD.
Rashin kyawun hasashen PAAD ya samo asali ne daga rashin juriya ga magungunan chemotherapy. A cikin 'yan shekarun nan, an yi amfani da magungunan hana garkuwar jiki sosai wajen magance ciwon daji [8]. Duk da haka, amfani da ICIs a cikin ciwon daji na pancreas ba kasafai yake samun nasara ba [9]. Saboda haka, yana da mahimmanci a gano marasa lafiya waɗanda za su iya amfana daga maganin ICI.
Dogon RNA mara lamba (lncRNA) wani nau'in RNA ne wanda ba ya lamba tare da nucleotides sama da 200. LncRNAs suna yaɗuwa kuma suna wakiltar kusan kashi 80% na transcriptome na ɗan adam [10]. Babban aikin ya nuna cewa samfuran hasashen da aka yi amfani da su ta hanyar lncRNA na iya yin hasashen hasashen majiyyaci yadda ya kamata [11, 12]. Misali, an gano lncRNAs 18 masu alaƙa da autophagy don samar da sa hannun hasashen a cikin ciwon nono [13]. An yi amfani da wasu lncRNAs shida masu alaƙa da garkuwar jiki don tabbatar da siffofin hasashen glioma [14].
A cikin ciwon daji na pancreas, wasu bincike sun tabbatar da sa hannun lncRNA don hasashen hasashen majiyyaci. An kafa sa hannun lncRNA mai 3-lncRNA a cikin adenocarcinoma na pancreas tare da yanki a ƙarƙashin lanƙwasa ROC (AUC) na 0.742 kawai da kuma rayuwa gabaɗaya (OS) na shekaru 3 [15]. Bugu da ƙari, ƙimar bayyanar lncRNA ya bambanta tsakanin kwayoyin halitta daban-daban, tsarin bayanai daban-daban, da marasa lafiya daban-daban, kuma aikin samfurin hasashen ba shi da tabbas. Saboda haka, muna amfani da sabon tsarin ƙira, haɗawa da maimaitawa, don samar da sa hannun lncRNA (irlncRNA) masu alaƙa da rigakafi don ƙirƙirar samfurin hasashen da ya fi daidaito da kwanciyar hankali [8].
An samo bayanan RNAseq da aka daidaita (FPKM) da kuma bayanan TCGA na ciwon daji na pancreas da kuma bayanin genotype nama (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 bayyanar lncRNA daga RNAseq. Mun sauke 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 alaƙa (p < 0.001, r > 0.4). Gano irlncRNAs masu alaƙa da bambanci (DEirlncRNAs) ta hanyar haɗa irlncRNAs da lncRNAs masu alaƙa da bambanci da aka samu daga bayanan GEPIA2 (http://gepia2.cancer-pku.cn/#index) a cikin ƙungiyar TCGA-PAAD (|logFC| > 1 da FDR) <0.05).
An bayar da rahoton wannan hanyar a baya [8]. Musamman, muna gina X don maye gurbin lncRNA A da lncRNA B da aka haɗa. Lokacin da ƙimar bayyanar lncRNA A ta fi ƙimar bayyanar lncRNA B, an ayyana X a matsayin 1, in ba haka ba an ayyana X a matsayin 0. Saboda haka, za mu iya samun matrix na 0 ko – 1. Axis na tsaye na matrix yana wakiltar kowane samfuri, kuma axis na kwance yana wakiltar kowane haɗin DEirlncRNA tare da ƙimar 0 ko 1.
An yi amfani da nazarin koma-baya na Univariate wanda ya biyo baya da kuma sake-sake na Lasso don tantance nau'ikan DEirlncRNA na hasashen. Binciken komawa-sake na lasso ya yi amfani da tantancewar giciye sau 10 da aka maimaita sau 1000 (p < 0.05), tare da abubuwan da ke haifar da bazuwar 1000 a kowace gudu. Lokacin da mitar kowace ma'auratan DEirlncRNA ta wuce sau 100 a cikin zagayowar 1000, an zaɓi ma'auratan DEirlncRNA don gina samfurin haɗarin hasashen. Sannan muka yi amfani da lanƙwasa na AUC don nemo mafi kyawun ƙimar yankewa don rarraba marasa lafiya na PAAD zuwa ƙungiyoyi masu girma da ƙananan haɗari. An kuma ƙididdige ƙimar AUC na kowane samfurin kuma an zana shi azaman lanƙwasa. Idan lanƙwasa ta kai matsayi mafi girma wanda ke nuna matsakaicin ƙimar AUC, tsarin lissafi ya tsaya kuma ana ɗaukar samfurin a matsayin mafi kyawun ɗan takara. An gina samfuran lanƙwasa na ROC na shekaru 1, 3 da 5. An yi amfani da nazarin komawa-sake na Univariate da multivariate don bincika aikin hasashen mai zaman kansa na samfurin haɗarin hasashen.
Yi amfani da kayan aiki guda bakwai don nazarin ƙimar shigar ƙwayoyin rigakafi, waɗanda suka haɗa da XCELL, TIMER, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, da CIBERSORT. An sauke bayanan shigar ƙwayoyin rigakafi daga bayanan TIMER2 (http://timer.comp-genomics.org/#tab-5817-3). An yi nazarin bambancin da ke cikin abubuwan da ke cikin ƙwayoyin rigakafi masu shiga tsakanin ƙungiyoyi masu girma da ƙananan haɗari na samfurin da aka gina ta amfani da gwajin matsayi na Wilcoxon, an nuna sakamakon a cikin jadawalin murabba'i. An yi nazarin hulɗar Spearman don nazarin alaƙar da ke tsakanin ƙimar maki haɗari da ƙwayoyin da ke shiga garkuwar jiki. An nuna ma'aunin haɗin gwiwa da ya haifar a matsayin lollipop. An saita ma'aunin mahimmanci a p < 0.05. An gudanar da aikin ta amfani da fakitin R ggplot2. Don bincika alaƙar da ke tsakanin samfurin da matakan bayyanar kwayoyin halitta da ke da alaƙa da ƙimar shigar ƙwayoyin rigakafi, mun yi fakitin ggstatsplot da kuma hangen nesa na zane-zanen violin.
Domin tantance yanayin maganin cutar kansar pancreas, mun ƙididdige IC50 na magungunan chemotherapy da aka saba amfani da su a cikin ƙungiyar TCGA-PAAD. An kwatanta bambance-bambancen da ke tsakanin rabin yawan hanawa (IC50) tsakanin ƙungiyoyi masu girma da ƙananan haɗari ta amfani da gwajin Wilcoxon mai sa hannu, kuma an nuna sakamakon a matsayin boxplots da aka samar ta amfani da pRRophetic da ggplot2 a cikin R. Duk hanyoyin sun bi ƙa'idodi da ƙa'idodi masu dacewa.
An nuna tsarin aikin bincikenmu a Hoto na 1. Ta amfani da nazarin alaƙa tsakanin lncRNAs da kwayoyin halittar da ke da alaƙa da rigakafi, mun zaɓi irlncRNAs 724 tare da p < 0.01 da r > 0.4. Na gaba mun yi nazarin lncRNAs masu bayyana daban-daban na GEPIA2 (Hoto na 2A). Jimillar irlncRNAs 223 an bayyana su daban-daban tsakanin adenocarcinoma na pancreas da nama na pancreas na yau da kullun (|logFC| > 1, FDR < 0.05), mai suna DEirlncRNAs.
Gina samfuran haɗarin da ake hasashensu. (A) Tsarin aman wuta na lncRNAs masu bayyana daban-daban. (B) Rarraba ma'aunin lasso don nau'ikan DEirlncRNA 20. (C) Bambancin yuwuwar ɓangare na rarraba ma'aunin LASSO. (D) Tsarin daji yana nuna nazarin koma-baya na univariate na nau'ikan DEirlncRNA 20.
Mun sake gina matrix 0 ko 1 ta hanyar haɗa DEirlncRNAs 223. An gano jimillar nau'ikan DEirlncRNA guda 13,687. Bayan nazarin univariate da lasso regression, an gwada nau'ikan DEirlncRNA guda 20 a ƙarshe don gina samfurin haɗarin hasashen (Hoto na 2B-D). Dangane da sakamakon Lasso da nazarin regression da yawa, mun ƙididdige maki na haɗari ga kowane majiyyaci a cikin ƙungiyar TCGA-PAAD (Tebur na 1). Dangane da sakamakon nazarin regression na lasso, mun ƙididdige maki na haɗari ga kowane majiyyaci a cikin ƙungiyar TCGA-PAAD. AUC na lanƙwasa ROC shine 0.905 don hasashen samfurin haɗari na shekara 1, 0.942 don hasashen shekaru 2, da 0.966 don hasashen shekaru 3 (Hoto na 3A-B). Mun sanya ƙimar yankewa mafi kyau ta 3.105, mun rarraba marasa lafiya na ƙungiyar TCGA-PAAD zuwa ƙungiyoyi masu yawa da ƙananan haɗari, kuma muka tsara sakamakon rayuwa da rarraba maki haɗari ga kowane majiyyaci (Hoto na 3C-E). Binciken Kaplan-Meier ya nuna cewa rayuwar marasa lafiya na PAAD a cikin rukunin masu haɗari ya yi ƙasa sosai fiye da na marasa lafiya a cikin rukunin masu haɗari (p < 0.001) (Hoto na 3F).
Ingancin samfuran haɗarin hasashen. (A) ROC na samfurin haɗarin hasashen. (B) samfuran haɗarin hasashen ROC na shekaru 1, 2, da 3. (C) ROC na samfurin haɗarin hasashen. Yana nuna mafi kyawun wurin yankewa. (DE) Rarraba yanayin rayuwa (D) da maki na haɗari (E). (F) Binciken Kaplan-Meier na marasa lafiya na PAAD a cikin ƙungiyoyi masu yawa da ƙananan haɗari.
Mun ƙara tantance bambance-bambance a cikin makin haɗari ta hanyar halayen asibiti. Tsarin tsiri (Hoto na 4A) yana nuna alaƙar gabaɗaya tsakanin halayen asibiti da makin haɗari. Musamman ma, tsofaffi marasa lafiya suna da makin haɗari mafi girma (Hoto na 4B). Bugu da ƙari, marasa lafiya da ke da makin mataki na II suna da makin haɗari mafi girma fiye da marasa lafiya da ke da makin mataki na I (Hoto na 4C). Dangane da makin ƙari a cikin marasa lafiya da ke da makin PAAD, marasa lafiya na aji na 3 suna da makin haɗari mafi girma fiye da marasa lafiya na aji na 1 da 2 (Hoto na 4D). Mun ƙara yin nazarin koma-baya na univariate da multivariate kuma mun nuna cewa makin haɗari (p < 0.001) da shekaru (p = 0.045) dalilai ne na hasashen masu zaman kansu a cikin marasa lafiya da ke da PAAD (Hoto na 5A-B). Tsarin ROC ya nuna cewa makin haɗari ya fi sauran halaye na asibiti wajen annabta tsawon shekaru 1, 2, da 3 na rayuwa ga marasa lafiya da ke da PAAD (Hoto na 5C-E).
Halayen asibiti na samfuran haɗarin hasashen. Histogram (A) yana nuna (B) shekaru, (C) matakin ƙari, (D) matakin ƙari, ƙimar haɗari, da jinsi na marasa lafiya a cikin ƙungiyar TCGA-PAAD. **p < 0.01
Nazarin hasashen yanayi mai zaman kansa na samfuran haɗarin hasashen yanayi. (AB) Nazarin juyawar Univariate (A) da multivariate (B) na samfuran haɗarin hasashen yanayi da halayen asibiti. (CE) ROC na shekaru 1, 2, da 3 don samfuran haɗarin hasashen yanayi da halayen asibiti
Saboda haka, mun bincika alaƙar da ke tsakanin lokaci da maki masu haɗari. Mun gano cewa maki masu haɗari a cikin marasa lafiya na PAAD yana da alaƙa da ƙwayoyin T na CD8+ da ƙwayoyin NK (Hoto na 6A), wanda ke nuna aikin garkuwar jiki da aka danne a cikin ƙungiyar masu haɗari. Mun kuma tantance bambanci a cikin shigar ƙwayoyin garkuwar jiki tsakanin ƙungiyoyi masu haɗari da masu haɗari kuma mun sami sakamako iri ɗaya (Hoto na 7). An sami ƙarancin shigar ƙwayoyin T na CD8+ da ƙwayoyin NK a cikin ƙungiyar masu haɗari. A cikin 'yan shekarun nan, an yi amfani da masu hana garkuwar jiki (ICIs) sosai wajen magance ciwon daji. Duk da haka, amfani da ICIs a cikin ciwon daji na pancreas ba kasafai yake samun nasara ba. Saboda haka, mun tantance bayyanar kwayoyin halittar gwajin rigakafi a cikin ƙungiyoyi masu haɗari da masu haɗari. Mun gano cewa CTLA-4 da CD161 (KLRB1) sun fi yawa a cikin ƙungiyar masu haɗari (Hoto na 6B-G), wanda ke nuna cewa marasa lafiya na PAAD a cikin ƙungiyar masu haɗari na iya zama masu saurin kamuwa da ICI.
Binciken daidaituwa na samfurin haɗarin hasashen da shigar ƙwayoyin rigakafi. (A) Alaƙa tsakanin samfurin haɗarin hasashen da shigar ƙwayoyin rigakafi. (BG) Yana nuna bayyanar kwayoyin halitta a cikin ƙungiyoyi masu haɗari da ƙananan haɗari. (HK) ƙimar IC50 don takamaiman magungunan hana ciwon daji a cikin ƙungiyoyi masu haɗari da ƙananan haɗari. *p < 0.05, **p < 0.01, ns = ba mahimmanci ba
Mun ƙara tantance alaƙar da ke tsakanin ma'aunin haɗari da magungunan chemotherapy na gama gari a cikin ƙungiyar TCGA-PAAD. Mun nemi magungunan hana ciwon daji da aka saba amfani da su a cikin ciwon daji na pancreas kuma mun bincika bambance-bambancen da ke cikin ƙimar IC50 tsakanin ƙungiyoyi masu girma da marasa haɗari. Sakamakon ya nuna cewa ƙimar IC50 na AZD.2281 (olaparib) ta fi girma a cikin rukunin masu haɗari, wanda ke nuna cewa marasa lafiyar PAAD a cikin rukunin masu haɗari na iya jure wa maganin AZD.2281 (Hoto na 6H). Bugu da ƙari, ƙimar IC50 na paclitaxel, sorafenib, da erlotinib sun yi ƙasa a cikin rukunin masu haɗari (Hoto na 6I-K). Mun ƙara gano magungunan hana ciwon daji 34 waɗanda ke da ƙimar IC50 mafi girma a cikin rukunin masu haɗari da kuma magungunan hana ciwon daji 34 waɗanda ke da ƙimar IC50 mafi girma a cikin rukunin masu haɗari (Tebur na 2).
Ba za a iya musanta cewa lncRNAs, mRNAs, da miRNAs suna wanzuwa sosai kuma suna taka muhimmiyar rawa a ci gaban cutar kansa ba. Akwai isassun shaidu da ke goyon bayan muhimmiyar rawar da mRNA ko miRNA ke takawa wajen hasashen rayuwa gaba ɗaya a cikin nau'ikan cutar kansa da dama. Babu shakka, samfuran haɗarin hasashen da yawa suma sun dogara ne akan lncRNAs. Misali, Luo et al. Bincike ya nuna cewa LINC01094 yana taka muhimmiyar rawa wajen yaduwar PC da metastasis, kuma yawan bayyanar LINC01094 yana nuna rashin lafiyar masu cutar kansar pancreas [16]. Binciken da Lin et al suka gabatar ya nuna cewa raguwar lncRNA FLVCR1-AS1 yana da alaƙa da mummunan hasashen a cikin marasa lafiya da cutar kansar pancreas [17]. Duk da haka, ba a tattauna lncRNAs masu alaƙa da rigakafi ba dangane da hasashen rayuwar marasa lafiya da cutar kansa gaba ɗaya. Kwanan nan, an mayar da hankali sosai kan gina samfuran haɗarin hasashen don annabta rayuwar marasa lafiya da cutar kansa ta haka kuma an daidaita hanyoyin magani [18, 19, 20]. Akwai ƙaruwar fahimtar muhimmancin shigar garkuwar jiki cikin fara cutar kansa, ci gaba, da kuma amsawa ga jiyya kamar chemotherapy. Nazarce-nazarce da dama sun tabbatar da cewa ƙwayoyin garkuwar jiki masu shiga cikin ƙwayoyin cuta suna taka muhimmiyar rawa wajen mayar da martani ga maganin chemotherapy mai guba [21, 22, 23]. Yanayin garkuwar jiki mai ƙarfi na ciwon daji muhimmin abu ne a cikin rayuwar marasa lafiya da ciwon daji [24, 25]. Ana amfani da maganin rigakafi, musamman maganin ICI, sosai wajen magance ciwon daji masu ƙarfi [26]. Ana amfani da kwayoyin halitta masu alaƙa da garkuwar jiki sosai don gina samfuran haɗarin hasashen. Misali, Su et al. Tsarin haɗarin hasashen hasashen ya dogara ne akan kwayoyin halitta masu alaƙa da furotin don annabta hasashen masu cutar kansar mahaifa [27]. Kwayoyin halitta marasa lamba kamar lncRNAs suma sun dace da gina samfuran haɗarin hasashen hasashen [28, 29, 30]. Luo et al sun gwada lncRNAs guda huɗu masu alaƙa da garkuwar jiki kuma sun gina samfurin hasashen haɗarin cutar kansar mahaifa [31]. Khan et al. An gano jimillar rubuce-rubuce 32 da aka bayyana daban-daban, kuma bisa ga wannan, an kafa samfurin hasashen da ke ɗauke da muhimman rubuce-rubuce guda 5, wanda aka gabatar a matsayin kayan aiki da aka ba da shawarar sosai don hasashen ƙin yarda da cutar bayan dashen koda da aka tabbatar da shi ta hanyar biopsy [32].
Yawancin waɗannan samfuran sun dogara ne akan matakan bayyanar kwayoyin halitta, ko dai kwayoyin halittar da ke ɗauke da sunadaran ko kwayoyin halittar da ba sa ɗauke da sunadaran. Duk da haka, kwayar halittar iri ɗaya na iya samun ƙimar bayyana daban-daban a cikin kwayoyin halitta daban-daban, tsarin bayanai da kuma a cikin marasa lafiya daban-daban, wanda ke haifar da ƙiyasin rashin daidaituwa a cikin samfuran hasashen. A cikin wannan binciken, mun gina samfuri mai ma'ana tare da nau'i biyu na lncRNAs, ba tare da la'akari da ainihin ƙimar bayyana ba.
A cikin wannan binciken, mun gano irlncRNA a karon farko ta hanyar nazarin alaƙa da kwayoyin halitta masu alaƙa da rigakafi. Mun tantance DEirlncRNAs 223 ta hanyar haɗakarwa tare da lncRNAs masu bayyana daban-daban. Na biyu, mun gina matrix 0-ko-1 bisa ga hanyar haɗin DEirlncRNA da aka buga [31]. Sannan muka yi nazarin univariate da lasso regression don gano nau'ikan DEirlncRNA na hasashen yanayi da kuma gina samfurin hasashen yanayi. Mun ƙara yin nazarin alaƙar da ke tsakanin makin haɗari da halayen asibiti a cikin marasa lafiya da PAAD. Mun gano cewa samfurin haɗarin hasashen yanayi, a matsayin abin da ke haifar da hasashen yanayi mai zaman kansa a cikin marasa lafiya da PAAD, zai iya bambanta marasa lafiya da ...
Masu bincike sun ba da rahoton cewa marasa lafiya da ke da yawan shigar ƙwayoyin CD8+ T sun fi saurin kamuwa da cutar ICI [33]. Ƙara yawan ƙwayoyin cytotoxic, ƙwayoyin NK na CD56, ƙwayoyin NK da ƙwayoyin CD8+ T a cikin yanayin garkuwar jiki na iya zama ɗaya daga cikin dalilan da ke haifar da tasirin rage girman ciwon [34]. Nazarin da aka yi a baya ya nuna cewa matakan CD4(+) T da CD8(+) T masu shiga cikin ciwon suna da alaƙa da tsawon rai [35]. Rashin shigar ƙwayoyin CD8 T, ƙarancin nauyin neoantigen, da kuma yanayin ciwon da ke rage ƙarfin garkuwar jiki yana haifar da rashin amsawa ga maganin ICI [36]. Mun gano cewa ƙimar haɗari tana da alaƙa mara kyau da ƙwayoyin CD8+ T da ƙwayoyin NK, wanda ke nuna cewa marasa lafiya da ke da yawan haɗarin ƙila ba su dace da maganin ICI ba kuma suna da mummunan hasashen.
CD161 alama ce ta ƙwayoyin halitta masu kisa (NK). Kwayoyin T da aka canza daga CD8+CD161+ suna daidaita ingancin maganin ƙari a cikin ƙwayoyin halittar HER2+ na pancreas ductal adenocarcinoma xenograft [37]. Masu hana garkuwar jiki suna kai hari ga hanyoyin cytotoxic T lymphocyte masu alaƙa da cytotoxic protein 4 (CTLA-4) da kuma 1 (PD-1)/wanda aka tsara don mutuwar ƙwayoyin halitta ligand 1 (PD-L1) kuma suna da babban damar a wurare da yawa. Bayyanar CTLA-4 da CD161 (KLRB1) yana da ƙasa a cikin ƙungiyoyi masu haɗari, wanda hakan ke nuna cewa marasa lafiya da ke da ƙimar haɗari mai yawa ƙila ba za su cancanci maganin ICI ba. [38]
Domin nemo hanyoyin magani da suka dace da marasa lafiya masu haɗarin kamuwa da cutar kansa, mun yi nazari kan magunguna daban-daban na maganin ciwon daji kuma mun gano cewa paclitaxel, sorafenib, da erlotinib, waɗanda ake amfani da su sosai a cikin marasa lafiya da ke fama da cutar PAAD, na iya dacewa da marasa lafiya masu haɗarin kamuwa da cutar PAAD. [33]. Zhang da abokan aikinsa sun gano cewa maye gurbi a cikin kowace hanyar amsawar lalacewar DNA (DDR) na iya haifar da mummunan hasashen ga marasa lafiya da ke fama da cutar kansar prostate [39]. Gwajin Ciwon Daji na Olaparib Ongoing (POLO) ya nuna cewa maganin kulawa tare da olaparib yana da tsawon rai ba tare da ci gaba ba idan aka kwatanta da placebo bayan maganin chemotherapy na platinum na farko a cikin marasa lafiya da ke fama da cutar kansar ductal adenocarcinoma da maye gurbi na BRCA1/2 [40]. Wannan yana ba da kyakkyawan fata cewa sakamakon magani zai inganta sosai a cikin wannan rukunin marasa lafiya. A cikin wannan binciken, ƙimar IC50 na AZD.2281 (olaparib) ya fi girma a cikin rukunin masu haɗarin kamuwa da cutar, yana nuna cewa marasa lafiya da ke cikin rukunin masu haɗarin kamuwa da cutar PAAD na iya jure wa magani tare da AZD.2281.
Samfuran hasashen da ke cikin wannan binciken suna samar da kyakkyawan sakamako na hasashen, amma sun dogara ne akan hasashen nazari. Yadda ake tabbatar da waɗannan sakamakon tare da bayanan asibiti muhimmiyar tambaya ce. Ɗaukar hoton allurar endoscopic fine needle aspiration (EUS-FNA) ya zama hanya mai mahimmanci don gano raunukan pancreas masu ƙarfi da waɗanda ba su cikin pancreas tare da jin daɗin kashi 85% da takamaiman kashi 98% [41]. Zuwan allurar EUS fine-needle biopsy (EUS-FNB) ya dogara ne akan fa'idodin da aka gani akan FNA, kamar ingantaccen ganewar asali, samun samfuran da ke kiyaye tsarin histological, don haka samar da kyallen garkuwar jiki wanda yake da mahimmanci ga wasu ganewar asali. Tabo na musamman [42]. Wani bita na tsari na wallafe-wallafen ya tabbatar da cewa allurar FNB (musamman 22G) suna nuna mafi girman inganci wajen tattara kyallen daga tarin pancreas [43]. A asibiti, ƙananan adadin marasa lafiya ne kawai suka cancanci tiyata mai tsauri, kuma yawancin marasa lafiya suna da ƙari marasa aiki a lokacin ganewar asali. A aikin asibiti, ƙaramin adadin marasa lafiya ne kawai suka dace da tiyata mai tsauri saboda yawancin marasa lafiya suna da ƙari marasa aiki a lokacin ganewar asali. Bayan tabbatar da cututtuka ta hanyar EUS-FNB da sauran hanyoyin, yawanci ana zaɓar maganin da ba na tiyata ba kamar chemotherapy. Shirin bincikenmu na gaba shine don gwada samfurin hasashen wannan binciken a cikin ƙungiyoyin tiyata da waɗanda ba na tiyata ba ta hanyar nazarin baya.
Gabaɗaya, bincikenmu ya kafa sabon samfurin haɗarin hasashen bisa ga haɗin irlncRNA, wanda ya nuna ƙimar hasashen hasashen ga marasa lafiya da ke fama da ciwon daji na pancreas. Tsarin haɗarin hasashenmu na iya taimakawa wajen bambance marasa lafiya da ke fama da PAAD waɗanda suka dace da maganin likita.
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Lokacin Saƙo: Satumba-22-2023