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Background: One of the deadliest and most prevalent cancer is pancreatic ductal adenocarcinoma (PDAC). Microarray has become an important tool in the research of PDAC genes and target therapeutic drugs., Objectives: This study intends to clarify the promising prognostic and biomarker targets in PDAC using GSE78229 and GSE62452 datasets, publicly accessible at the Gene Expression Omnibus database., Materials and Methods: Utilizing GEOquery, Bio base, gplots, and ggplot2 packages in the R program, this study detects 428 differentially expressed genes that are further applied to build a co-expression network by the weighted correlation network analysis (WGCNA). The turquoise module presented a higher correlation with PDAC progression. 79 candidate genes were selected based on the co-expression and protein-protein interaction (PPI) networks. In addition, the functional enrichment analysis was studied., Results: Five significant KEGG pathways linked to PDAC were detected, in which the endoplasmic reticulum protein processing pathway was remarked to be vital. The resulting 19 hub genes as HSPA4, PABPC1, HSP90B1, PPP1CC, USP9X, EIF2S3, MSN, RAB10, BMPR2, P4HB, UBC, B2M, SLC25A5, MMP7, SPTBN1, RALB, DNAJB1, CENPE, and PDIA6 were identified by the Network Analyst web tool founded on PPI network by the STRING. These were identified as the most connected hub proteins. The quantification of the expression of levels and survival probabilities were analyzed overall survival (OS) of the real hub genes and were investigated by Kaplan-Meier (KM) plotter through The Cancer Genome Atlas Program (TCGA) database., Conclusions: The protein-protein interactions and KEGG pathway enrichment by DAVID indicated that some pathways were involved in PDAC, such as "pathways in cancer (hsa05200)", "protein processing in the endoplasmic reticulum (hsa04141)", "antigen processing and presentation (hsa04612)", "dopaminergic synapse (hsa04728)", and "measles (hsa05162)"; in which these pathways, the "protein processing in endoplasmic reticulum (hsa04141)", was further studied because of its closely relationship with PDAC. The rest of the hub genes reviewed throughout the study might be promising targets for diagnosing and treating PDAC and relevant diseases., (Copyright: © 2021 The Author(s); Published by Iranian Journal of Biotechnology.)