Objective: The main reasons for the poor prognoses of pancreatic adenocarcinoma (PA) patients are rapid early-stage progression, advanced stage metastasis, and chemotherapy resistance. Identification of novel diagnostic and prognostic biomarkers of PA is therefore urgently needed.Methods: Three mRNA microarray datasets were obtained from the Gene Expression Omnibus database to select differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses for hub genes were performed using DAVID. Correlations between expression levels of hub genes and cancer-infiltrating immune cells were investigated by TIMER. Cox proportional hazard regression analyses were also performed. Serum hub genes were screened using the HPA platform and verified for diagnostic value using ELISAs. Results: We identified 59 hub genes among 752 DEGs. GO analysis indicated that these 59 hub genes were mainly involved in the defense response to viruses and the type I interferon signaling pathway. We also discovered that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment. Additionally, DLGAP5 mRNA might be used as an independent risk factor for the prognoses of PA patients. Furthermore, the protein encoded by ISG15, which exists in peripheral blood, was validated as a potential diagnostic biomarker that distinguished PA patients from healthy controls (area under the curve: 0.902, 95％ confidence interval: 0.819–0.961). Conclusions: Our study suggested that RSAD2 and SMC4 were associated with immune cell infiltration in the PA microenvironment, while DLGAP5 mRNA expression might be an independent risk factor for the survival prognoses of PA patients. Moreover, ELISAs indicated that serum ISG15 could be a potential novel diagnostic biomarker for PA.

Duo Zuo;Yongzi Chen;Xinwei Zhang;Zhuozhi Wang;Wenna Jiang;Fan Tang;Runfen Cheng;Yi Sun;Lu Sun;Li Ren;Rui Liu

Department of Clinical Laboratory;Department of Tumor Cell Biology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China;School of Biomedical Engineering,Tianjin Medical University,Tianjin 300070,China;Department of Pathology,Tianjin Huanhu Hospital,Tianjin 300350,China;Department of Pathology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China;School of Pharmacy,Tianjin Medical University,Tianjin 300070,China;Department of Gastrointestinal Medical Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin,Tianjin's Clinical Research Center for Cancer,Tianjin 300060,China

癌症生物学与医学（英文版）

[1]Duo Zuo;Yongzi Chen;Xinwei Zhang;Zhuozhi Wang;Wenna Jiang;Fan Tang;Runfen Cheng;Yi Sun;Lu Sun;Li Ren;Rui Liu-.Identification of hub genes and their novel diagnostic and prognostic significance in pancreatic adenocarcinoma)[J].癌症生物学与医学（英文版）,2022(07):1029-1046

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