Expression and prognostic significance of MT1 isoforms in clear cell renal cell carcinoma

Xiaohua Niu,Ling Deng,Dexiang Zhuo,Chaoming Tang

doi:10.12688/f1000research.22996.1

Xiaohua Niu, Ling Deng + Show 2 more

Open Access

https://doi.org/10.12688/f1000research.22996.1

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Abstract

Metallothioneins (MTs), a family of low-weight cysteine-rich proteins, play key roles in tumor biology, such as proliferation, differentiation, apoptosis, and drug resistance. Clinical studies have demonstrated that deregulation of MTs in various types of solid cancers. However, a comprehensive overview of MT1 isoforms expression and clinical relevance in clear cell renal cell cancer (ccRCC) is lacking. The present study explored mRNA expression levels and prognostic values of MT1 isoforms in ccRCC tissues using The Cancer Genome Atlas (TCGA), Gene Expression Profiling and Interactive Analysis (GEPIA) and Oncomine database. The study observed that mRNA expression levels of six members of MT1 isoforms decreased in renal cancer tumor tissues compared with normal tissues. We further found that high-expression of MT1G, MT1H, MT1F and MT1X was related with poor overall survival time in ccRCC patients and high-expression of MT1G, MT1F and MT1X were inversely associated with disease-free survival time in ccRCC patients. Based on the correlation analysis, MT1G was identified to be co-expressed with MT1H and MT1F in ccRCC tissues. These findings suggested that MT1 isoforms mRNA may serve as diagnostic and prognostic markers for ccRCC.

Highlights

Clear cell renal cell carcinoma is the most common type of renal tumor, which approximately constitutes 3% of adult malignancies and accounts for 90% of all renal malignancies[1,2]
We found that mRNA expression levels of six MT1 isoforms, including MT1G, MT1H, MT1F, MT1X, MT1E and MT1M were simultaneously decreased in Clear cell renal cell carcinoma (ccRCC) tumor tissues compared with normal tissues (Figure 1)
Using data from The Cancer Genome Atlas (TCGA)-KIRC, we found that mRNA expression levels of MT1G, MT1H, MT1F, MT1X, MT1E and MT1M were simultaneously decreased in ccRCC tumor tissues compared with normal tissues

Summary

Introduction

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal tumor, which approximately constitutes 3% of adult malignancies and accounts for 90% of all renal malignancies[1,2]. Metallothioneins (MTs) are a family of cysteine-rich proteins. Their molecular weight ranges from 6 to 7 kDa and they play essential roles in tumor biology such as proliferation, differentiation, apoptosis, and drug-resistance[6,7,8,9,10,11]. MT1 isoform profiling had been utilized as diagnostic markers and as prognostic predictors of tumor diseases[12,13,14]. Lots of work has been performed regarding the expression and prognostic value of MT1 isoforms in ccRCC19–22. There was still not enough information about the expression and prognostic value of the MT1 isoforms in ccRCC. It would be of great importance to elucidate the pattern of MT1 isoform expression and evaluate their prognostic value in ccRCC for patients’ benefits

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