Abstract
Objects:
Colorectal cancer (CRC) is the third most prevalent cancer globally and the second leading cause of cancer-related mortality. This study aims to investigate the expression of REEP6 (Receptor-expression enhancing protein 6) and its association with molecular interactions, immune infiltration, and patient survival across colorectal cancer.
Materials and methods
Data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, including datasets GSE89076, GSE37364, and GSE20916 for validation. RNA sequencing data were normalized using the DESeq2 R package, while microarray data underwent background correction and normalization via the Robust Multi-array Average method. Batch effects were corrected using the Combat method. Differentially expressed genes (DEGs) were identified based on |log2 Fold Change| > 1.5 and adjusted p-value < 0.05. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses were conducted using the Cluster Profiler R package. Correlation analyses employed Spearman's rank correlation coefficient. Kaplan-Meier survival analysis was performed to evaluate patient outcomes, and ROC (Receiver Operating Characteristic) curve analysis assessed model performance. Immune infiltration was analyzed in relation to REEP6 expression.
Results
REEP6 expression is significantly elevated in colorectal cancer samples compared to normal tissues (P < 0.001). ROC analysis revealed an area under the curve of 0.880, indicating high diagnostic potential. DEGs associated with REEP6 included UPK1A, SLC7A9, SLC22A31, and NLRP6, all positively correlated with REEP6 expression. Enrichment analyses suggested these genes are involved in nucleosome formation and DNA packaging complexes, implicating systemic lupus erythematosus and alcoholism pathways. Although Kaplan-Meier survival curves showed no significant difference in overall survival between high and low REEP6 expression groups (HR = 1.31, P = 0.133), immune infiltration analysis indicated increased NK CD56bright cell levels in high REEP6 expression samples (R = 0.333558, P < 0.001).
Conclusion
REEP6 is highly expressed in colorectal cancer and correlates with specific molecular pathways and immune cell infiltration but does not significantly impact patient survival outcomes alone. These findings highlight REEP6's potential as a diagnostic biomarker and suggest further research into its role in cancer immunology is warranted.