Low expression of ZHX3 is associated with progression and poor prognosis in colorectal cancer

Abstract

Accumulating studies suggest that ZHX3, the member of ZHX family, is involved in a variety of biological functions such as development and differentiation. Recently, ZHX3 may also be involved in the progression of several cancer types including renal cancer, gastric cancer, liver cancer and breast cancer. However, the potential role of ZHX3 in colorectal cancer (CRC) is still unknown. In this study, we analyzed the protein levels of ZHX3 by immunohistochemistry and evaluated its relationship with the clinicopathological features and prognosis in 286 CRC patients. In vitro cell proliferation assay, plate colony formation assay and xenograft model in nude mice were applied to evaluate CRC cell proliferative ability. Our results showed that the expression of ZHX3 was significantly downregulated in CRC tissues compared with paired adjacent nontumor tissues. Furthermore, the ZHX3 expression was found to have a strong correlation with tumor size, tumor invasion depth and TNM stage. Kaplan-Meier analysis demonstrated that low ZHX3 expression was related to a poorer overall survival and disease-free survival in CRC patients. In addition, cox's proportional hazards analysis indicated that low ZHX3 expression was an independent prognostic indicator of poor prognosis. Functionally, reduced expression of ZHX3 promotes the proliferation of CRC cells both in vitro and in vivo. Conversely, overexpression of ZHX3 inhibited the growth of CRC cells, indicated that ZHX3 was significantly correlated with CRC progression. Our results indicate for the first time that ZHX3 may be a potential marker of cancer prognosis and CRC recurrence.