Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

Ryuk-Jun Kwon; Yun Hak Kim; Dae Cheon Jeong; Myoung-Eun Han; Ji-Young Kim; Liangwen Liu; Jin-Sup Jung; Sae-Ock Oh

doi:10.1371/journal.pone.0171036

Expression and prognostic significance of zinc fingers and homeoboxes family members in renal cell carcinoma

PLoS One. 2017 Feb 2;12(2):e0171036. doi: 10.1371/journal.pone.0171036. eCollection 2017.

Authors

Ryuk-Jun Kwon^{1

2}, Yun Hak Kim^{1

2}, Dae Cheon Jeong³, Myoung-Eun Han^{1

2}, Ji-Young Kim^{1

2}, Liangwen Liu^{1

2}, Jin-Sup Jung⁴, Sae-Ock Oh^{1

2}

Affiliations

¹ Departments of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
² Gene & Therapy Research Center for Vessel-associated Diseases, Pusan National University, Yangsan, Republic of Korea.
³ Department of Statistics, Korea University, Seongbuk-gu, Seoul, Republic of Korea.
⁴ Departments of Physiology, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Abstract

Zinc fingers and homeoboxes (ZHX) is a transcription repressor family that contains three members; ZHX1, ZHX2, and ZHX3. Although ZHX family members have been associated with the progression of cancer, their values as prognostic factors in cancer patients have been poorly examined. Renal cell carcinoma (RCC) is a highly heterogeneous, aggressive cancer that responds variably to treatment. Thus, prognostic molecular markers are required to evaluate disease progression and to improve the survival. In clear cell RCC (ccRCC), ZHX1 and ZHX3 expression were found to be down-regulated but ZHX2 was up-regulated, and the expressions of ZHX1 and ZHX3 were significantly associated with pathological stage. Furthermore, Kaplan-Meier and multivariate regression analysis showed that reduction in the mRNA expression of ZHX1 was associated with poorer survival. Taken together, the present study shows loss of ZHX1 is correlated with ccRCC progression and suggests it is an independent prognostic marker in ccRCC.

MeSH terms

Aged
Carcinoma, Renal Cell / genetics*
Carcinoma, Renal Cell / mortality
Carcinoma, Renal Cell / pathology
Female
Gene Expression Regulation, Neoplastic
Genes, Homeobox
Homeodomain Proteins / genetics*
Humans
Kaplan-Meier Estimate
Kidney Neoplasms / genetics*
Kidney Neoplasms / mortality
Kidney Neoplasms / pathology
Male
Middle Aged
Prognosis
Repressor Proteins / genetics*
Transcription Factors / genetics*
Zinc Fingers

Substances

Homeodomain Proteins
Repressor Proteins
Transcription Factors
ZHX1 protein, human
ZHX2 protein, human
ZHX3 protein, human

Grants and funding

This work was supported by by the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIP) (NRF-2016R1A2B4014593), the Medical Research Center (MRC) Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2015R1A5A2009656) and a grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (0920050). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.