The Downregulation of Prognosis- and Immune Infiltration-Related Gene CYFIP2 Serves as a Novel Target in ccRCC

Abstract

Background: Increasing evidence indicated that the aberrant expression of the cytoplasmic FMR1-interacting protein (CYFIP) family might possess critical role and potential functions in cancer. But the role of CYFIP2 in clear cell renal cell carcinoma (ccRCC) is still uncharacteristic. Methods: We investigated the Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for the expression profile, clinicopathological variables, clinical prognosis information, and promoter methylation levels of CYFIPs in ccRCC. The aberrant CYFIP2 protein expression was validated by the Human Protein Atlas (HPA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to uncover CYFIP2 mRNA levels in 28 pairs of ccRCC cancer tissues. Kaplan-Meier analysis, univariate and multivariate Cox proportional hazard regression were performed to assess CYFIPs' prognosis value. Gene set enrichment analysis (GSEA) was used to determined hallmark functions, gene ontology of CYFIP2. TIMER database was utilized to assess the correlation with immune infiltration in ccRCC. Results: Results showed CYFIP2 was downregulated in ccRCC, relative to paired normal tissues in TCGA-KIRC database and 28 pairs of clinical samples (P < 0.0001). Similarly, a decreased CYFIP2 protein expression was confirmed by ccRCC tissues. The results showed CYFIP2 was negatively regulated by promoter DNA methylation. Survival analysis results showed CYFIP2 could be an independent biomarker for ccRCC and its reduction predicted a poor overall survival (OS) and disease-free survival (DFS). GSEA showed CYFIP2 was involved in metabolic pathways and epithelial-mesenchymal transition (EMT). Immune infiltration analysis revealed that a list of immune markers was significantly correlated with CYFIP2 expression especially with CD4+ cells and CD8+ cells in ccRCC. Conclusion:These results show that CYFIP2 was downregulated in ccRCC patients and predicted an unfavorable prognosis. CYFIP2 might be a potential novel prognostic molecule, and related to immune infiltration, the metabolism, as well as EMT process in ccRCC. CYFIP2 could act as tumor suppressor gene in ccRCC and positive modulation of CYFIP2 might lead to development of a novel strategy for ccRCC treatment.

Expression and Potential Biomarkers of Regulators for M7G RNA Modification in Gliomas

“…In addition, Saller et al reported CYFIP2 as a candidate p53 target gene in H1299 lung cancer cells ( 46 ), and Jackson et al verified in DLD1 colorectal adenocarcinoma cells that CYFIP2 can act as a p53-inducible gene to promote apoptosis in colorectal adenocarcinoma cells ( 47 ). Also, Tong et al found that CYFIP2 expression was decreased in clear cell renal cell carcinoma and was associated with poorer clinicopathological parameters of clear cell renal cell carcinoma patients ( 48 ). CYFIP2 activates the cell death program to inhibit the proliferation of tumor cells, indicating that CYFIP2 is a potent tumor suppressor.…”

A Novel 7-Methylguanosine (m7G)-Related Gene Signature for Overall Survival Prediction in Patient with Clear Cell Renal Cell Carcinoma

“…Recent research demonstrated that Cyfp 2 might play a critical role and have potential functions in cancers, such as gastric cancer [29] and colorectal adenocarcinoma [30]. Previous studies indicated CYFIP2 was downregulated in ccRCC patients due to its DNA methylation, and it was involved in the metabolic reprogramming, the EMT pathway, and immune infltration processes in ccRCC by its DNA methylation [31]. Te eukaryotic initiation factor 4A (eIF4A) family plays a vital role in many cancers [32][33][34].…”

Analysis and Experimental Validation of Rheumatoid Arthritis Innate Immunity Gene CYFIP2 and Pan-Cancer

“…A meta-analysis unearthed that CYFIP2 was upregulated and validated in peripheral blood mononuclear cell samples of RA patients, creating a novel gene signature in RA diagnostic and therapeutic interventions ( 30 ). An investigation focused on the downregulation of CYFIP2 in clear cell renal cell carcinoma (ccRCC) revealed that several immune markers were critically correlated with CYFIP2 expression, especially with CD4+ cells and CD8+ cells, which could act as a tumor suppressor gene in ccRCC and create a novel strategy in clinical treatment ( 31 ). Except for RCC, current research about CYFIP2 was mainly concentrated on neurons and encephalopathy ( 32 , 33 ), and more attention should be paid to RA.…”