Comprehensive study of the tumor immune microenvironment and the prognostic significance of reticulocalbin-1: a pan-cancer analysis

Reticulocalbin-1 (RCN1), an endoplasmic reticulum (ER)-related gene, demonstrates critical regulatory functions in cellular growth. RCN1 has been previously revealed to be closely associated with initiation, metastasis and chemosensitivity in some tumors. However, the prognostic significance of RCN1 and its influence on the cancer immune microenvironment remains unclear. By leveraging multi-omics data from TCGA and GEO, this study delineated the expression profile of RCN1 across various human malignancies and normal tissues. Analysis of RCN1 expression in correlation with tumor immune microenvironment characteristics was performed using CIBERSORT and ssGSEA. Pan-cancer prognostic value was assessed via multiple survival models. In glioma, immunohistochemistry, co-culture, and qPCR were utilized to further investigate the role of RCN1 in tumor immunity and prognosis. Drug-specific responses to RCN1 expression were probed for cisplatin, irinotecan, carmustine and lomustine, which are the common chemotherapeutic agents used in glioma clinical treatment. The results indicate that RCN1 is a key gene with the potential to promote the progression of multiple tumors and is closely associated with tumor immune response, particularly macrophage activation. In glioma, overexpression of RCN1 promotes tumor proliferation and indicates poor prognosis, and is closely related to endoplasmic reticulum stress. Knockdown of RCN1 enhances the chemotherapeutic efficacy of carmustine and lomustine. In conclusion, our research positioned RCN1 as an important oncogene from a pan-cancer perspective and validated its role in glioma. In particular, RCN1 is closely associated with the immune microenvironment and endoplasmic reticulum stress during tumorigenesis. In addition, RCN1 has broad prospects in guiding tumor chemotherapy pending physiological in vivo validation.