Identification and Validation of RORC as a Circadian Rhythm-Related Biomarker in Gastric Cancer

Purpose: Gastric cancer (GC) represents a malignant neoplasm with high global incidence and mortality rates. The limited efficacy of current clinical treatment regimens underscores the urgent need for novel and more effective therapeutic targets. Patients and Methods: Through the utilization of public databases, we identified circadian rhythm genes associated with GC and conducted an analysis of their expression profiles. Enrichment analysis was performed using the KEGG/GO pathways via the "clusterProfiler" package, immune correlation was assessed through ssGSEA (GSVA), tumor mutations were analyzed using TCGA somatic data, and drug sensitivity was evaluated using the "pRRophetic" package. The biological functions of RORC in GC cells were investigated through CCK8, colony formation, and Transwell assays. Results: RORC has been identified as a pivotal gene associated with circadian modulation in gastric cancer. Its expression is markedly reduced in gastric cancer tissues compared to adjacent normal tissues. Enrichment analysis indicates a significant correlation between RORC and the regulation of circadian rhythms. Immunocorrelation analysis demonstrates a significant association between RORC gene expression and T follicular helper cells (Tfh), T cell co-stimulation, and activated dendritic cells (aDCs). Analysis of mutations related to the RORC gene reveals that missense mutations are the predominant type. Notably, key genes such as TP53 and ARID1A show relatively high mutation frequencies in both high and low RORC expression groups. Drug sensitivity analysis indicates that the RORC gene is responsive to agents such as VX-680, MG-132, and Sunitinib. Cell biology experiments have confirmed that RORC overexpression significantly diminishes the proliferation, invasion, and migration capabilities of gastric cancer cells. Conclusion: Integrating bioinformatics and cell biology experiments suggests that RORC, a gene associated with rhythm regulation, acts as a tumor suppressor gene that is underexpressed in gastric cancer, thereby serving as a potential biomarker and therapeutic target for this malignancy.