DYSF expression in clear cell renal cell carcinoma: A retrospective study of 2 independent cohorts

Mihyang Ha; Hoim Jeong; Jong Seong Roh; Beomgu Lee; Myoung-Eun Han; Sae-Ock Oh; Dong Hyun Sohn; Yun Hak Kim

doi:10.1016/j.urolonc.2019.07.007

DYSF expression in clear cell renal cell carcinoma: A retrospective study of 2 independent cohorts

Urol Oncol. 2019 Oct;37(10):735-741. doi: 10.1016/j.urolonc.2019.07.007. Epub 2019 Jul 31.

Authors

Mihyang Ha¹, Hoim Jeong², Jong Seong Roh², Beomgu Lee², Myoung-Eun Han¹, Sae-Ock Oh¹, Dong Hyun Sohn³, Yun Hak Kim⁴

Affiliations

¹ Department of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of Korea.
² Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea.
³ Department of Microbiology and Immunology, Pusan National University School of Medicine, Yangsan, Republic of Korea. Electronic address: dhsohn@pusan.ac.kr.
⁴ Department of Anatomy and Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea; Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. Electronic address: yunhak10510@pusan.ac.kr.

PMID: 31377166
DOI: 10.1016/j.urolonc.2019.07.007

Abstract

Objective: Renal cell carcinoma (RCC) is the most typical type of kidney cancer in adults. Hypercalcemia is a well known paraneoplastic syndrome associated with RCC and recent studies have reported that hypercalcemia is closely related to the poor prognosis of RCC patients. Clear cell RCC (ccRCC) is the most common and aggressive subtype of RCC. Although the histological classification of RCC is important for determination of appropriate treatment strategies, effective biomarkers for predicting prognosis of ccRCC have not yet been identified. Since calcium levels affect the prognosis of RCC patients, we evaluated whether the calcium-sensing genes on the plasma membrane, including those encoding calcium channels, CaSR, GPRC6a, and DYSF, could be used as biomarkers to predict the prognosis of ccRCC patients.

Methods: Information from 537 patients from The Cancer Genome Atlas (TCGA; n = 446) and International Cancer Genome Consortium (ICGC; n = 91) was used in this study. Among these genes, DYSF was the only gene whose expression correlated with overall survival of both TGCA and ICGC patients.

Results: Although DYSF gene expression was higher in ccRCC tissue than in normal kidney tissue, Kaplan-Meier curves showed that the survival rate of ccRCC patients with high DYSF expression was significantly higher than that of patients with low DYSF expression (TCGA, P < 0.0001; ICGC, P = 0.0011). We also validated the potential of DYSF as a prognostic biomarker for ccRCC by conducting a time-dependent area under the curve (AUC) analysis and 5-years receiver operating characteristic curve analysis. Finally, multivariate regression analysis revealed that the expression of DYSF is independent of other prognostic parameters (TCGA, P = 0.017; ICGC, P = 0.006).

Conclusions: These results suggested that DYSF may play a suppressive role in the progression of ccRCC and could act as a promising prognostic biomarker for predicting the survival of ccRCC patients.

Keywords: Clear cell renal cell carcinoma; DYSF; ICGC; Prognostic marker; TCGA.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carcinoma, Renal Cell / genetics*
Dysferlin / metabolism
Female
Humans
Kidney Neoplasms / genetics*
Male
Middle Aged
Prognosis
Retrospective Studies

Substances

DYSF protein, human
Dysferlin