Abstract
Thyroid cancer incidence has increased in recent decades. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. Approximately 30% of PTC patients develop recurrence or distant metastasis and tend to have poor prognosis. Therefore, the identification of targetable biomarkers in this subset of patients is of great importance. Accumulating evidence indicates that zinc finger protein 677 (ZNF677), which belongs to the zinc finger protein family, is an important effector during the progression of multiple malignancies. However, its role in Middle Eastern PTC patients has not been fully illustrated. Here, we uncovered the molecular mechanism and the clinical impact of ZNF677 expression in a large cohort of more than 1200 Middle Eastern PTC and 15 metastatic tissues. We demonstrated that ZNF677 is frequently downregulated in primary PTC (13.6%, 168/1235) and showed that complete loss of expression of ZNF677 is significantly associated with aggressive clinico-pathological markers such as extrathyroidal extension (p = 0.0008) and distant metastases (p < 0.0001). We also found a significantly higher incidence of ZNF677 loss in primary tumors with distant metastases (33.3%; p < 0.0001) as well as in distant metastatic tissues (46.7%; p = 0.0002) compared to the overall cohort (13.6%). More importantly, PTC with loss of ZNF677 expression showed significantly lower metastasis-free survival (p = 0.0090). Interestingly, on multivariate logistic regression analysis, ZNF677 loss was an independent predictor of distant metastasis in PTC (Odds ratio = 2.60, 95% Confidence interval = 1.20–5.62, p = 0.0155). In addition, we found a significant association between ZNF677 loss and phospho-AKT expression (p < 0.0001). Our functional molecular results suggest that ZNF677 acts as a tumor suppressor, mediating its effect by inhibiting AKT phosphorylation. Taken together, our results highlight the pivotal role played by ZNF677 during carcinogenesis and metastasis formation in Middle Eastern PTC patients.
Highlights
Since we found a significant association of zinc finger protein 677 (ZNF677) loss with distant metastasis, we further analyzed the incidence of
ZNF677 loss in primary cases with distant metastasis (n = 72) and found a statistically significant difference in the incidence of ZNF677 loss between this subset of patients and the overall cohort (33.3% vs. 13.6%, p < 0.0001)
We demonstrated in our Papillary thyroid carcinoma (PTC) patient cohort that complete loss of ZNF677 protein expression is significantly associated with aggressive clinico-pathological parameters such as extrathyroidal extension and distant metastasis
Summary
Thyroid cancer is the most common endocrine malignancy, with a recent rapid increase in its incidence [1,2,3,4]. Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancers and is known to have favorable prognosis [3,5,6]. Up to 15% of PTC patients were found to develop distant metastases [7,8,9,10] after initial therapy, which was the main cause of thyroid cancer-related deaths [11,12,13,14]. Disease-specific mortality rates at 10 years for patients with distant metastasis is 70% [15]. Distant metastasis is considered the most important prognostic factor for PTC patients.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
