Comprehensive analysis of MFN2 as a prognostic biomarker associated with immune cell infiltration in renal clear cell carcinoma

Abstract

Background: Treatment of advanced kidney renal clear cell carcinoma (KIRC) remains challenging in clinic. The functional role and prognostic significance of MFN2 in KIRC are still unclear.

Methods: In this study, we first performed a bioinformatic analysis to determine the expression level and prognostic value of MFN2 in KIRC using The Cancer Genome Atlas (TCGA) dataset, and then validated the MFN2 mRNA expression in our cohort of clinical tissue samples and cell lines of KIRC via RT-qPCR. Cox regression model was used to identify the independent prognostic factors. A nomogram was constructed to predict the prognosis of KIRC patients. Gene set enrichment analysis (GSEA) was performed to predict the involved functional pathways of MFN2 co-expressed genes. The association between MFN2 expression level and immune cell infiltration was assessed using the TIMER and the TIDISB databases. In addition, cell proliferation and migration abilities of two KIRC cell lines with MFN2 overexpression were evaluated by MTS and wound healing assays, respectively.

Results: Downregulation of MFN2 was observed in KIRC tissues and cell lines compared to the normal controls. Kaplan-Meier curve analysis indicated an inferior survival outcomes in KIRC patients with lower MFN2 expression, uncovering the tumor-suppressive role of MFN2 in KIRC. Cox regression results showed that higher MFN2 expression was one of the independent protective factors in KIRC. Besides, function predictive analysis revealed that MFN2 co-expressed genes were enriched in the biological processes of energy metabolism and autophagy. Moreover, MFN2 expression was observed to be significantly associated with immune cell infiltration and a variety of markers of tumor infiltrating immune cells (TIICs) including multiple immune checkpoints in KIRC tissues. Finally, MFN2 overexpression significantly inhibited cell proliferation and migration abilities of two KIRC cell lines examined.

Conclusion: Generally, our data suggested that MFN2 may serve as a potential prognostic biomarker and therapeutic target in KIRC.

Keywords: Immune cell infiltration; MFN2; Prognostic biomarker; Renal clear cell carcinoma.