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

Date Published: February 2, 2017

Publisher: Public Library of Science

Author(s): Ryuk-Jun Kwon, Yun Hak Kim, Dae Cheon Jeong, Myoung-Eun Han, Ji-Young Kim, Liangwen Liu, Jin-Sup Jung, Sae-Ock Oh, Hiromu Suzuki.


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.

Partial Text

Renal cell carcinoma(RCC) is the most common type of cancer originating from the renal cortex[1], and is classified according to its pathological characteristics. Renal clear cell carcinoma (ccRCC) is the most common subtype;other subtypes include papillary, chromophobe, collecting duct, and unclassified RCC[2]. The incidence rates of RCCs have been steadily increasing at a rate of 2 to 4% per year over past decades[3]. Karnofksy performance status, low level of hemoglobin, elevated platelet count, and elevated corrected calcium are known as risk factors in RCC, and poor risk patients have a 2-year overall survival of only 7%[4]. Furthermore, patients often show poor or partial response to traditional chemotherapy and radiation therapy[5], and thus, despite treatment advances made, RCC remains a highly aggressive and often fatal disease. To improve the poor survival of ccRCC, new therapeutic or prognostic markers need to be developed.

ZHX family members has been described as tumor suppressor genes in several studies, but their prognostic relevance has been poorly characterized. The present study shows for the first time that ZHX1 and ZHX3 are upregulated and ZHX2 is downregulated and suggests that ZHX1 and ZHX3 be considered independent prognostic markers in ccRCC.

The present study shows expression of ZHX family members is correlated with ccRCC progression and prognosis. The study suggests that ZHX1 is a new independent prognostic marker in ccRCC.




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