The transcriptional repressor cAMP response element modulator (CREM) has an important role in T-cell development. In this study, we used the integrated Bioinformatics Methods to explore the role of CREM in gastric adenocarcinoma (GAC). Our results showed that high CREM expression was closely related with poorer overall survival in GAC. By GSEA cluster analysis, we found that the high expression of CREM was associated with the cancer-associated pathway in GAC. Moreover, single-cell sequencing data showed that CREM is mainly localized in exhausted CD8+ T cells. Its prognostic value and the potential function lead to T-cell exhaustion in the tumor microenvironment (TME). Similar results were also obtained in glioma and lung cancer. High expression of CREM, correlated with clinical relevance of GAC, was associated with T-cell exhaustion and M2 polarization in GAC. These findings suggest that CREM can be used as a prognostic biomarker in GAC, which might provide a novel direction to explore the pathogenesis of GAC.

Bladder cancer (BC) is one of the most common cancers worldwide. T-cell immunoglobulin and mucin domain 1 (TIM-1) is involved in the progression of multiple tumors. The role of TIM-1 in BC progression is poorly understood. In the present study, we searched the Gene Expression Profiling Interactive Analysis (GEPIA) database and performed immunohistochemistry (IHC) to assess TIM-1 protein expression in bladder cancer (BC) patients. The results demonstrated that BC with high TIM-1 expression was associated with longer overall survival (OS) and disease-specific survival (DSS) than BC with low TIM-1 expression. Overexpression of TIM-1 inhibited BC cell proliferation in both cell culture and animal experiments. RNA sequencing data indicated that interferon-induced protein with tetratricopeptide repeats (IFIT) genes induced by interferon-α (IFN-α) were significantly enriched among the genes upregulated by overexpression of TIM-1. Mechanistically, our data revealed that TIM-1 promoted IFN-α release and activated the IFIT2/p-STAT1 pathway, which is known to be related to tumor cell proliferation. Moreover, knockdown of IFIT2 in TIM-1-overexpressing BC cells hindered the tumor suppressive effect of TIM-1. Our results revealed TIM-1 as a potential molecular marker for prognosis in BC and indicate that high TIM-1 expression suppresses BC cell proliferation in an IFIT2/p-STAT1-dependent manner.