A comprehensive pancancer analysis reveals the potential value of RAR-related orphan receptor C (RORC) for cancer immunotherapy

Abstract

Background: RAR-related orphan receptor C (RORC) plays an important role in autoimmune responses and inflammation. However, its function in cancer immunity is still unclear. Its potential value in cancer immunotherapy (CIT) needs to be further studied.Methods: Expression and clinical data for 33 cancers were obtained from UCSC-Xena. The correlation between RORC expression and clinical parameters was analyzed using the limma software package to assess the prognostic value of RORC. Timer2.0 and DriverDBv3 were used to analyze the RORC mutation and methylation profiles. RORC-associated signaling pathways were identified by GSEA. The correlations of RORC expression with tumor microenvironment factors were further assessed, including immune cell infiltration (obtained by CIBERSORT) and immunomodulators (in pancancer datasets from the Tumor-Immune System Interactions and Drug Bank [TISIDB] database). In addition, the correlations of RORC with four CIT biomarkers (tumor mutational burden, microsatellite instability, programmed death ligand-1, and mismatch repair) were explored. Furthermore, three CIT cohorts (GSE67501, GSE168204, and IMvigor210) from the Gene Expression Omnibus database and a previously published study were used to determine the association between RORC expression and CIT response.Results: RORC was differentially expressed in many tumor tissues relative to normal tissues (20/33). In a small number of cancers, RORC expression was correlated with age (7/33), sex (4/33), and tumor stage (9/33). Furthermore, RORC expression showed prognostic value in many cancers, especially in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and mesothelioma (MESO). The mutation rate of RORC in most cancer types was low, while RORC was hypermethylated or hypomethylated in multiple cancers. RORC was associated with a variety of biological processes and signal transduction pathways in various cancers. Furthermore, RORC was strongly correlated with immune cell infiltration, immunomodulators, and CIT

Prognostic and immunological significance of metastasis-associated protein 3 in patients with thymic epithelial tumors

“…S5B). Given that RORC has previously been associated with immune cell infiltration in TETs [ 39 ] and that MTA3 has previously been implicated in immune response regulation [ 19 – 22 ], we focused on the role of MTA3 in TETs. We found that MTA3 was significantly downregulated in thymic tumors (Fig.…”

Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity

“…A previous study has shown that the neuropeptide nociceptin/orphanin' FQ (N/OFQ) has been identified as a promising immunomodulator for inflammatory bowel diseases [37]. RORC, the core genes of the circadian clock, is a critical transcription factor for Th17 polarization and function, and it plays a significant role in autoimmunity and inflammation [38,39]. It is proved that RORC mRNA expression was increased in patients with UC [40,79].…”

Circadian clock-related genome-wide Mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity

“…A previous study has shown that the neuropeptide nociceptin/orphanin' FQ (N/OFQ) has been identi ed as a promising immunomodulator for in ammatory bowel diseases (34). RORC is a critical transcription factor for Th17 polarization and function, and it plays a signi cant role in autoimmunity and in ammation (35). It is proved that RORC mRNA expression was increased in patients with UC(36).…”