CREM Is Correlated With Immune-Suppressive Microenvironment and Predicts Poor Prognosis in Gastric Adenocarcinoma

Abstract

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.

Single-Cell Profiling Comparisons of Tumor Microenvironment between Primary Advanced Lung Adenocarcinomas and Brain Metastases and Machine Learning Algorithms in Predicting Immunotherapeutic Responses

“…TF analyses for each T cluster identified CREM and NFKB1 activated specifically in CD8+ Trm (Figure 2D). CREM was found to be correlated with immune-suppressive microenvironment, thus partly explaining the greater anti-cancer efficacy of CD8+ Trm by ICIs [30]. Additionally, the activation of NFKB1 also indicated the construction of a proinflammatory microenvironment by CD8+ Trm.…”

Multi-Omics Integration-Based Prioritisation of Competing Endogenous RNA Regulation Networks in Small Cell Lung Cancer: Molecular Characteristics and Drug Candidates

“…The KEGG pathway analysis was performed to analyse the potential pathways enriched by the differentially expressed lncRNA, circRNAs, miRNAs and mRNAs. The enrichment analysis was evaluated using the R package ClusterProfiler ( 45 ), for which we considered an adjusted p < 0.05 as statistically significant ( 46 ).…”

Landscapes and mechanisms of CD8+ T cell exhaustion in gastrointestinal cancer

“…Elevated serum interleukin-8 (sIL-8) prominently originated from GC-associated fibroblasts upregulates PD-1 expression in CD8 + T cells via activating JAK2/STAT3 signaling and inhibiting PD-1 ubiquitination through Fbxo38 down-regulation, leading to (103,104). Transcriptional repressor cAMP response element modulator (CREM) is induced by cAMP signaling pathway and positively correlated with exhausted marker genes in gastric adenocarcinoma (105). Dexamethasone suppress the transcription of PD-L1 and IDO1 via nuclear translocation of GR/STAT3 complex to inhibit TEX and immune evasion in coculture system, 3D organoid model and humanized mouse model (106).…”

“…FoxP3 + Tregs in GC tissues can decompose ATP to adenosine with CD39 and CD73, and then adenosine interactives with A2aR to induce apoptosis and inhibit immune response and proliferation of CD8 + T cells ( 103 , 104 ). Transcriptional repressor cAMP response element modulator (CREM) is induced by cAMP signaling pathway and positively correlated with exhausted marker genes in gastric adenocarcinoma ( 105 ). Dexamethasone suppress the transcription of PD-L1 and IDO1 via nuclear translocation of GR/STAT3 complex to inhibit TEX and immune evasion in coculture system, 3D organoid model and humanized mouse model ( 106 ).…”