PMID- 34007003 OWN - NLM STAT- MEDLINE VI - 11 IP - 1 TI - ITGA2, LAMB3, and LAMC2 may be the potential therapeutic targets in pancreatic ductal adenocarcinoma: an integrated bioinformatics analysis. PG - 10563 LA - eng PT - Journal Article PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 IS - 2045-2322 (Electronic) LID - 10.1038/s41598-021-90077-x [doi] FAU - Islam, Shajedul AU - Islam S AUID- ORCID: 0000-0002-4939-1001 AD - Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. FAU - Kitagawa, Takao AU - Kitagawa T AD - Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. FAU - Baron, Byron AU - Baron B AD - Centre for Molecular Medicine and Biobanking, University of Malta, Msida, MSD 2080, Malta. FAU - Abiko, Yoshihiro AU - Abiko Y AD - Division of Oral Medicine and Pathology, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. FAU - Chiba, Itsuo AU - Chiba I AD - Division of Disease Control and Molecular Epidemiology, Department of Oral Growth and Development, School of Dentistry, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. FAU - Kuramitsu, Yasuhiro AU - Kuramitsu Y AD - Advanced Research Promotion Center, Health Sciences University of Hokkaido, 1757 Kanazawa, Ishikari-Tobetsu, Hokkaido, 061-0293, Japan. climates@hoku-iryo-u.ac.jp. IS - 2045-2322 (Linking) RN - 0 (Cell Adhesion Molecules) RN - 0 (ITGA2B protein, human) RN - 0 (Integrin alpha2) RN - 0 (LAMC2 protein, human) RN - 0 (Laminin) RN - 0 (RNA, Messenger) SB - IM MH - Carcinoma, Pancreatic Ductal/*genetics/pathology/*therapy MH - Cell Adhesion Molecules/*genetics MH - Computational Biology/*methods MH - Datasets as Topic MH - Gene Expression Profiling MH - Humans MH - Integrin alpha2/*genetics MH - Laminin/*genetics MH - Pancreatic Neoplasms/*genetics/pathology/*therapy MH - RNA, Messenger/genetics MH - Signal Transduction MH - Survival Analysis MH - Kalinin PMC - PMC8131351 DCOM- 20211108 LR - 20231213 DP - 20210518 DEP - 20210518 AB - Pancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer with an abysmal prognosis rate over the last few decades. Early diagnosis and prevention could effectively combat this malignancy. Therefore, it is crucial to discover potential biomarkers to identify asymptomatic premalignant or early malignant tumors of PDAC. Gene expression analysis is a powerful technique to identify candidate biomarkers involved in disease progression. In the present study, five independent gene expression datasets, including 321 PDAC tissues and 208 adjacent non-cancerous tissue samples, were subjected to statistical and bioinformatics analysis. A total of 20 differentially expressed genes (DEGs) were identified in PDAC tissues compared to non-cancerous tissue samples. Gene ontology and pathway enrichment analysis showed that DEGs were mainly enriched in extracellular matrix (ECM), cell adhesion, ECM-receptor interaction, and focal adhesion signaling. The protein-protein interaction network was constructed, and the hub genes were evaluated. Collagen type XII alpha 1 chain (COL12A1), fibronectin 1 (FN1), integrin subunit alpha 2 (ITGA2), laminin subunit beta 3 (LAMB3), laminin subunit gamma 2 (LAMC2), thrombospondin 2 (THBS2), and versican (VCAN) were identified as hub genes. The correlation analysis revealed that identified hub genes were significantly interconnected. Wherein COL12A1, FN1, ITGA2, LAMB3, LAMC2, and THBS2 were significantly associated with PDAC pathological stages. The Kaplan-Meier survival plots revealed that ITGA2, LAMB3, and LAMC2 expression were inversely correlated with a prolonged patient survival period. Furthermore, the Human Protein Atlas database was used to validate the expression and cellular origins of hub genes encoded proteins. The protein expression of hub genes was higher in pancreatic cancer tissue than in normal pancreatic tissue samples, wherein ITGA2, LAMB3, and LAMC2 were exclusively expressed in pancreatic cancer cells. Pancreatic cancer cell-specific expression of these three proteins may play pleiotropic roles in cancer progression. Our results collectively suggest that ITGA2, LAMB3, and LAMC2 could provide deep insights into pancreatic carcinogenesis molecular mechanisms and provide attractive therapeutic targets.