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

Autor: Siraj AK; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Parvathareddy SK; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Siraj N; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Al-Obaisi K; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Aldughaither SM; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., AlManea HM; Department of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., AlHussaini HF; Department of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Al-Dayel F; Department of Pathology, King Faisal Specialist Hospital and Research Centre, P.O. Box 3354, Riyadh, 11211, Saudi Arabia., Al-Kuraya KS; Human Cancer Genomic Research, Research Center, King Faisal Specialist Hospital and Research Center, MBC#98-16, P.O. Box 3354, Riyadh, 11211, Saudi Arabia. kkuraya@kfshrc.edu.sa.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Nov 16; Vol. 11 (1), pp. 22346. Date of Electronic Publication: 2021 Nov 16.
DOI: 10.1038/s41598-021-01869-0
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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