Author:
Zhang Bin,Han Dali,Yang LiMing,He Yang,Yang Shujun,Wang Hongbo,Zhang Xingxing,Du Yuelin,Xiong Wei,Ha Hualan,Shang Panfeng
Abstract
Abstract
Background
Mitofusin 2 (MFN2) plays an important role in many tumors, but how its role in renal clear cell carcinoma needs further research.
Methods
In this study, we analyzed the expression of MFN2 in renal clear cell carcinoma tissues and normal kidney tissues through the Cancer Genome Atlas (TCGA) database and our clinical samples.Enrichment analysis was performed to determine MFN2-related pathways and biological functions. The correlation of MFN2 expression with immune cells was analyzed.The correlation of the expression of methylation and the methylation sites of MFN2 were analyzed by UALCAN and TCGA databases. Univariate / multivariate COX risk regression and Kaplan-Meier methods were used to determine the prognostic value of MFN2.Nomograms were drawn to predict overall survival (OS) at 1,3, and 5 years. We investigated the role of MFN2 in renal cancer cells using CCK 8, clone formation, wound healing assay, and methylase qPCR experiments.
Results
MFN2 is poorly expressed in renal clear cell carcinoma compared to normal kidney tissue,and is significantly negatively associated with TNM stage, histological grade and pathological stage.MFN2 was directly associated with OS after multivariate Cox regression analysis.MFN2 shows a hypomethylation state and shows a positive correlation with multiple methylation sites.Signaling pathways through functional enrichment to B-cell receptors and oxidative stress-induced senescence.Moreover, the low expression of MFN2 was positively correlated with the degree of immune cell infiltration in a variety of immune cells.In vitro experiments showed that overexpression of MFN2 significantly inhibited the proliferation and migration of renal clear cells and promoted methylation.
Conclusions
In conclusion, MFN2 can be used as a novel prognostic marker for renal clear cell carcinoma and requires further investigation of its role in tumor development.
Funder
Special fund project for doctoral training program of Lanzhou University Second Hospital
CuiYing Science and Technology Innovation plan project of Lanzhou University Second Hospital
Medical Innovation and Development Project of Lanzhou University
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference40 articles.
1. Siegel RL, Miller KD, Fuchs HE, et al. Cancer Stat 2021 CA Cancer J Clin. 2021;71:7–33. https://doi.org/10.3322/caac.21654.
2. Cancer Stat Facts SEER. Kidney and Renal Pelvis Cancer. Bethesda, MD: National Cancer Institute. Accessed June 28., 2019. Available at: http://seer.cancer.gov/statfacts/html/kidrp.html.
3. Moch H, Gasser T, Amin MB, et al. Prognostic utility of the recently recommended histologic classification and revised TNM staging system of renal cell carcinoma: a swiss experience with 588 tumors. Cancer. 2000;89:604–14. PMID: 10931460.
4. Leibovich BC, Lohse CM, Crispen PL, et al. Histological subtype is an independent predictor of outcome for patients with renal cell carcinoma. J Urol. 2010;183:1309–15. https://doi.org/10.1016/j.juro.2009.12.035.
5. Lipworth L, Morgans AK, Edwards TL, et al. Renal cell cancer histological subtype distribution differs by race and sex. BJU Int. 2016;117:260–5. https://doi.org/10.1111/bju.12950.
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献