Comprehensive Analysis of Competing Endogenous RNA Network in T3 Colorectal Cancer Lymph Node Involvement

Abstract

Background: Lymph node involvement in T₃M₀ colorectal cancer (CRC) results in different treatments and prognoses, although the underlying mechanisms are still unclear. This study aimed to investigate the role of competing endogenous RNAs (ceRNA) in the mechanism. Methods: Differentially expressed genes were identified by comparing the transcription profiling in 83 T₃N₀M₀ versus 83 T₃N₊M₀ CRC. The ceRNA network was constructed based on the regulation of lncRNA-miRNA and miRNA-mRNA recorded in databases. Functional enrichment and overall survival analysis were then performed. Protein-Protein Interaction (PPI) Network was established to screen out hub genes and related ceRNA regulation axis. The correlation between the hub genes and immune infiltration was calculated. Results: A total of 595 DEmRNAs were identified, which were significantly enriched in cell adhesion, migration, and differentiation-associated biological processes. The similar method was used to identify 157 DElncRNAs and 15 DEmiRNAs, and a ceRNA network consisting of 17 DElncRNAs, four DEmiRNAs, and 36 DEmRNAs was constructed. The ceRNA network was associated with the regulation of homophilic cell adhesion via plasma membrane adhesion molecules, cell differentiation, and communication. A total of 13 members of the ceRNA network were associated with the outcomes of T₃ CRC patients. DRD1 and MYH11 not only participated in the ceRNA network but were hub genes. External validation cohort GSE39582 confirmed that DRD1 was up-regulated explicitly in T₃ CRC but not in T₂ and T₄. Additionally, hub genes DRD1 and MDM2 may induce an immunosuppressive microenvironment by reducing the infiltration of CD8⁺T cells and cytotoxic cells. Conclusions: The ceRNA network, especially for DRD1-related lncRNAs-miRNAs, modulates T₃ CRC lymph node involvement by affecting the adhesion and migration processes and the immune microenvironment.