ZFP91 zinc finger protein expression pattern in normal tissues and cancers

Abstract Background: Nasopharyngeal carcinoma (NPC) is a common type of cancer mainly caused by EB virus infection in southern China and Southeast Asia. Zinc finger protein of the cerebellum 2 has been reported to be dysregulated in numerous cancers. However, its role in NPC has not yet been completely investigated. Methods: ZIC2 mRNA expression and clinical role of NPC was explored by Gene Expression Omnibus (GEO) databases and tissue microarrays. Immunohistochemical (IHC) staining was used to assessed the protein expression level of ZIC2 in NPC. Moreover, functional enrichment analyses were performed by the overlapping genes of differentially expressed genes in NPC and ZIC2 related co-expressed genes. Cistrome Data Browser (Cistrome DB) and scatter diagrams displayed the possibility of ATAD2 as a target gene of ZIC2. Last, characteristic phenotype was identified by weighted gene co-expression network analysis (WGCNA).Results: The mRNA expression levels of ZIC2 were significantly increased in NPC within genechips and tissue microarrays (SMD = 2.14; 95% CI = 1.85–2.44). Increased ZIC2 correlated with poor prognosis in NPC patients. The IHC results also showed that ZIC2 protein expression in NPC tissues was remarkably higher than in control tissues. Enrichment analysis showed that genes positively related to ZIC2 are mainly enriched in cell division and in the cell cycle. WGCNA analysis discovered that NPC dataset GSE12452 may be positive correlated with N stage and nagetive correlated with grade. Conclusion: ZIC2 upregulation may promote NPC tumorigenesis through cancer cell proliferation and cell cycle regulation. ATAD2 may produce a marked effect as the downstream target of ZIC2.

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Loss of ZNF677 expression is a predictive biomarker for lymph node metastasis in Middle Eastern Colorectal Cancer

Scientific Reports ◽

10.1038/s41598-021-01869-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Abdul K. Siraj ◽

Sandeep Kumar Parvathareddy ◽

Nabil Siraj ◽

Khadija Al-Obaisi ◽

Saud M. Aldughaither ◽

...

Keyword(s):

Colorectal Cancer ◽

Lymph Node ◽

Protein Expression ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Middle Eastern ◽

Clinical Prognosis ◽

Mesenchymal Transition ◽

Finger Protein ◽

Potential Biomarker

AbstractZinc-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.

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