4.7 Article

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

Journal

INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 111, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.intimp.2022.109169

Keywords

MFN2; Renal clear cell carcinoma; Immune cell infiltration; Prognostic biomarker

Ask authors/readers for more resources

In this study, the researchers investigated the functional role and prognostic significance of MFN2 in kidney renal clear cell carcinoma (KIRC). They found that downregulation of MFN2 was associated with inferior survival outcomes in KIRC patients. MFN2 was also shown to be involved in energy metabolism and autophagy, and associated with immune cell infiltration and immune checkpoints in KIRC tissues. Moreover, overexpression of MFN2 inhibited cell proliferation and migration in KIRC cell lines. These findings suggest that MFN2 may serve as a potential prognostic biomarker and therapeutic target in KIRC.
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 prog-nostic 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 func-tional 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 ther-apeutic target in KIRC.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available