Integrin alpha L (ITGAL) is a member of the integrin family in which the abnormal expression is linked with carcinogenesis and immune regulation. However, the relation between ITGAL and the prognosis of gastric cancer (GC) and tumor-infiltrating lymphocytes (TILs) are not well understood. The differential expressions of ITGAL in human tumors and the clinical prognosis in GC were systematically analyzed via multiple databases including Gene Expression Profiling Interaction Analysis (GEPIA), UALCAN, Tumor Immune Estimation Resource (TIMER), and Kaplan-Meier (KM) plotter. TIMER, GEPIA, and TISIDB databases were used to comprehensively investigate the correlation between ITGAL and tumor infiltration immune cells. Also, further results were investigated by immunohistochemistry, qRT-PCR, and Western blot. We found that ITGAL expression in GC samples was considerably increased than in peritumor samples. Sample type, subgroup, cancer stage, lymphatic node stage, and worse survival were strongly related to high ITGAL expression. Moreover, upregulated ITGAL expression was strongly connected with immunomodulators, chemokines, and infiltrating levels of CD8+, CD4+ T cell, B cell, monocyte, neutrophil, macrophage, T-cell regulatory, NK cell, and myeloid dendritic cell in stomach adenocarcinoma (STAD). Specifically, immunohistochemistry and bioinformatic analysis showed that ITGAL expression was shown to have strong relationships with various immunological marker sets including PD1 (T-cell exhaustion marker). In conclusion, ITGAL is a prognostic biomarker for GC patients. It might regulate tumor immune microenvironment leading to poor prognosis. Furthermore, studies are essential to explore therapeutic targeting ITGAL.
Keywords: PD-1; gastric cancer; integrin alpha L (ITGAL); prognosis; tumor immune microenvironment; tumor-associated macrophages.
Copyright © 2022 Zhang, Wang, Yuan, Wu, Xu, Chen, Zhang and He.