Characterization of the prognostic and oncologic values of ITGB superfamily members in pancreatic cancer

• Published in: Journal of cellular and molecular medicine 2020-11, Vol.24 (22), p.13481-13493
• Main Authors: Zhuang, Hongkai, Zhou, Zixuan, Ma, Zuyi, Li, Zhenchong, Liu, Chunsheng, Huang, Shanzhou, Zhang, Chuanzhao, Hou, Baohua
• Format: Article
• Language: English
• Subjects: AP-2 protein; Binding sites; Biomarkers, Tumor; CD8+ T cells; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Computational Biology - methods; Correlation analysis; Databases, Genetic; Datasets; Disease Susceptibility; DNA Methylation; FHL2 protein; Gene expression; Gene Expression Regulation, Neoplastic; Genomes; Humans; immune infiltration; Immunosuppression; Immunotherapy; Integrins - genetics; Integrins - metabolism; ITGB superfamily members; Kaplan-Meier Estimate; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Lymphocytes, Tumor-Infiltrating - pathology; Medical prognosis; Multigene Family; Neoplasm Grading; Neoplasm Staging; Original; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Prognosis; Promoter Regions, Genetic; Proportional Hazards Models; ROC Curve; Signal transduction; Software; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocyte Subsets - pathology; Wnt protein
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15990

Integrin β (ITGB) superfamily members have been reported to play important roles in multiple biological functions in various cancers. However, the prognostic and oncologic values of ITGB superfamily members have not been systematically investigated in pancreatic cancer (PC). In this study, the mRNA expression and biological functions of ITGB superfamily members in PC were evaluated by bioinformatic analysis. Our results demonstrated that ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were significantly associated with advanced AJCC stage and histologic grade, and worse prognosis in PC. A prognostic signature based on ITGB1, ITGB4, ITGB5 and ITGB6 showed a reliable predictive performance. Furthermore, one CpGs (cg20545410) in promoter region of ITGB1, four (cg18709893, cg15700850, cg20667796 and cg18326022) of ITGB4, two (cg10977398 and cg03518058) of ITGB5 and one (cg23008083) of ITGB6 were negatively associated with their corresponding mRNA expression, and positively associated with prognosis in PC. We also identified TFAP2A as the potential transcription factor for ITGB4, SP1 for ITGB1 and ITGB6, and FHL2 for ITGB5 and ITGB6. ITGB1, ITGB4, ITGB5 and ITGB6 overexpressions were all significantly involved in focal adhesion signalling pathway. ITGB1 and ITGB5 overexpressions also associated with up‐regulation of TGF‐β and WNT signalling pathway, whereas ITGB4 and ITGB6 overexpressions associated with up‐regulation of Notch signalling pathway. Besides, ITGB1, ITGB5 and ITGB6 overexpressions significantly correlated with immunosuppression in PC. In summary, our study investigated the multilevel prognostic and biological values of ITGB superfamily members in PC.