Loss of CDH16 expression is a strong independent predictor for lymph node metastasis in Middle Eastern papillary thyroid cancer.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 10 2023
29 10 2023
Historique:
received:
12
03
2023
accepted:
25
10
2023
medline:
31
10
2023
pubmed:
30
10
2023
entrez:
30
10
2023
Statut:
epublish
Résumé
Papillary Thyroid Cancer (PTC) is the most common type of thyroid cancer. The membrane-associated glycoprotein cadherin-16 (CDH16) plays a significant role in the embryonal development of thyroid follicles and cell adhesion. Previous studies have indicated a substantial downregulation of CDH16 in PTC. However, its role in Middle Eastern PTC has not been elucidated. We analyzed a tissue microarray comprising 1606 PTC and 240 normal thyroid tissues using immunohistochemistry to assess CDH16 expression and determine its clinico-pathological associations. We also conducted BRAF and TERT mutations analyses through Sanger sequencing. Disease-free survival (DFS) was assessed using Kaplan-Meier curves. CDH16 immunostaining was seen in 100% of normal thyroid tissues but only in 9.4% of PTC tissues (p < 0.0001). The loss of CDH16 expression was associated with aggressive PTC characteristics including bilaterality, multifocality, extrathyroidal extension, tall cell variant, lymph node metastasis (LNM) and distant metastasis. Additionally a correlation between loss of CDH16 expression and BRAF and TERT mutations was identified. Intriguingly, upon conducting multivariate logistic regression analysis, CDH16 was determined to be an independent predictor for LNM (Odds ratio = 2.46; 95% confidence interval = 1.60-3.79; p < 0.0001). Furthermore, CDH16 loss was associated with a shorter DFS (p = 0.0015). However, when we further subdivided CDH16 negative patients based on the co-existence of TERT and/or BRAF mutations, we found that patients with both CDH16 negative expression and TERT mutation exhibited the shortest DFS (p < 0.0001). In conclusion, our results suggest that CDH16 protein expression could serve as a valuable diagnostic tool for PTC. Furthermore, these findings demonstrate that the loss of CDH16 expression is an independent predictor of LNM and may contribute to the aggressiveness of PTC. Therefore, downregulation of CDH16 in PTC might be a potential target for designing novel therapeutic strategies to treat PTC.
Identifiants
pubmed: 37899424
doi: 10.1038/s41598-023-45882-x
pii: 10.1038/s41598-023-45882-x
pmc: PMC10613612
doi:
Substances chimiques
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
CDH16 protein, human
0
Cadherins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
18559Informations de copyright
© 2023. The Author(s).
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