Comprehensive analysis of clinical features, mRNA splicing, and immunological role of REEP5 in esophageal squamous cell carcinoma

Oct 28, 2024Scientific reports

REEP5's clinical traits, gene processing, and immune role in esophageal squamous cell cancer

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Abstract

High expression is associated with poor prognosis in esophageal squamous cell carcinoma () patients.

REEP5 was significantly enriched in ESCC tissues compared to normal tissues.
Gene Ontology analysis indicated strong correlations between REEP5 and mRNA splicing and protein stabilization processes.
Positive correlations were observed between REEP5 and mRNA spliceosome assembly and disassembly through Gene Set Enrichment Analysis.
REEP5 expression was positively associated with cancer-inhibitory immune checkpoints CTLA-4, TIM-3, and HVEM.
Single-cell clustering revealed a close relationship between REEP5 expression and T-cell infiltration, particularly in CD8+ T-cells.
REEP5 may play a crucial role in immune responses mediated by Mast cells or T-cells in ESCC.

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Esophageal squamous cell carcinoma () is a prevalent malignancy within the digestive system, characterized by high incidence and mortality rates. The biological role of in ESCC progression remains poorly understood, despite its associations with various diseases, potentially accelerating tumor malignancy. We retrieved RNA-seq data and clinical information from 179 ESCC patients from the Gene Expression Omnibus (GEO) and 93 patients from The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses were conducted to explore the biological functions of REEP5 in ESCC, its role in the tumor microenvironment, and its prognostic value. Additionally, utilizing single-cell RNA-seq (scRNA-seq) data from 3 ESCC patients in the GEO database, we performed cluster analyses to investigate cell-specific expression differences of REEP5 between cancerous and adjacent non-cancerous tissues. Molecular biology experiments were also conducted to validate REEP5 expression disparities between tumor and non-tumor tissues. Compared to normal tissues, REEP5 was significantly enriched in ESCC tissues. High REEP5 expression was closely associated with poor prognosis in ESCC patients. Gene Ontology (GO) analysis revealed strong correlations between REEP5 and processes such as mRNA splicing and protein stabilization. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicated positive correlations between REEP5 and mRNA spliceosome assembly and disassembly. Pearson correlation analysis demonstrated positive associations between REEP5 and cancer-inhibitory immune checkpoints CTLA-4, TIM-3, and HVEM. Single-cell clustering and CIBERSORT analysis showed that REEP5 expression was closely related to T-cell infiltration in ESCC, with significant enrichment effects observed in CD8+ T-cell infiltration. REEP5 expression is closely correlated with the pathological and molecular pathology of ESCC, potentially playing a crucial role in Mast cell or T-cell-mediated immune responses in ESCC. Therefore, REEP5 holds promise as a novel therapeutic target for ESCC.

Key numbers

1261 days

Overall Survival Comparison

Median survival for patients with high expression in the GEO database.

1.48×

Expression Increase

Mean relative expression level of in cancerous vs. adjacent normal tissue.

20%

T-cell Infiltration Association

Comparison of immune cell infiltration levels in vs. adjacent normal tissues.

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Comprehensive analysis of clinical features, mRNA splicing, and immunological role of REEP5 in esophageal squamous cell carcinoma

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