Abstract
Zinc-finger proteins are transcription factors with a “finger-like” domain that are widely involved in many biological processes. The zinc-finger protein 677 (ZNF677) belongs to the zinc-finger protein family. Previous reports have highlighted the tumor suppressive role of ZNF677 in thyroid and lung cancer. However, its role in colorectal cancer (CRC) has not been explored. ZNF677 protein expression was analyzed by immunohistochemistry in a large cohort of 1158 CRC patients. ZNF677 loss of expression was more frequent in CRC tissues (45.3%, 525/1158), when compared to that of normal tissue (5.1%, 11/214) (p < 0.0001) and was associated with mucinous histology (p = 0.0311), advanced pathological stage (p < 0.0001) and lymph node (LN) metastasis (p = 0.0374). Further analysis showed ZNF677 loss to be significantly enriched in LN metastatic CRC compared to overall cohort (p = 0.0258). More importantly, multivariate logistic regression analysis showed that ZNF677 loss is an independent predictor of LN metastasis in CRC (Odds ratio = 1.41; 95% confidence interval 1.05–1.87; p = 0.0203).The gain- and loss-of-function studies in CRC cell lines demonstrated that loss of ZNF677 protein expression prominently increased cell proliferation, progression of epithelial-mesenchymal transition and conferred chemoresistance, whereas its overexpression reversed the effect. In conclusion, loss of ZNF677 protein expression is common in Middle Eastern CRC and contributes to the prediction of biological aggressiveness of CRC. Therefore, ZNF677 could not only serve as a marker in predicting clinical prognosis in patient with CRC but also as a potential biomarker for personalized targeted therapy.
Highlights
Colorectal cancer (CRC) is the second most common cause of cancer related deaths worldwide[1,2]
zinc-finger protein 677 (ZNF677) loss was noted in 45.3% (525/1158) of colorectal cancer (CRC) (Fig. 1A,B), compared to 5.1% (11/214) in normal colonic tissues (Fig. 1C,D) and this difference was statistically significant (p < 0.0001)
Loss of ZNF677 expression was significantly associated with adverse clinico-pathological parameters such as mucinous histology (p = 0.0311), T3/4 tumors (p < 0.0001), lymph node metastasis (p = 0.0374) and advanced stage (p < 0.0001), whereas no association was found with carcinoembryonic antigen (CEA) levels (p = 0.2519), BRAF (p = 0.0748), KRAS (p = 0.3429) or NRAS (p = 0.0944) mutations (Table 2)
Summary
Colorectal cancer (CRC) is the second most common cause of cancer related deaths worldwide[1,2]. Zinc-finger (ZNF) proteins are transcription factors with “fingerlike” domain that are involved in a wide variety of biological processes such as cell proliferation, differentiation and apoptosis, maintaining tissue homeostasis[10,11]. ZNF677 is a member of the Kruppel C 2H2-type zinc-finger protein family which has been shown to be frequently down regulated by promoter methylation in non-small cell lung cancer (NSCLC) and thyroid cancer[20,21]. The relevance of ZNF677 expression was analyzed using immunohistochemical staining in a large cohort (1158 patient tissues) of Middle Eastern CRC and explored the functional role of ZNF677 in CRC cell lines. We explored the correlation between ZNF677 expression and clinico-pathological parameters and sought to determine if ZNF677 could be utilized as a biomarker to predict lymph node metastasis in CRC
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
