Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance

  • Authors:
    • Fan Yang
    • Dongchen Liu
    • Yupeng Deng
    • Jun Wang
    • Shuyu Mei
    • Shuang Ge
    • Hailing Li
    • Cuijuan Zhang
    • Tingguo Zhang
  • View Affiliations

  • Published online on: March 19, 2020     https://doi.org/10.3892/ol.2020.11467
  • Pages: 3602-3608
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Abstract

Homeobox D 10 (HOXD10) is important in cell differentiation and morphogenesis and serves as a tumor suppressor gene (TSG) in a number of malignancies. The present study investigated its promoter methylation status and association with the clinicopathological features of endometrial cancer (EC), and measured HOXD10 protein expression levels. EC samples (n=62), including 50 endometroid adenocarcinoma (EA) and 12 mucinous endometrial carcinoma samples (EC) and 70 non‑cancerous samples were collected. All samples were evaluated for the methylation status of several TSGs, including HOXD10, using methylation‑specific PCR. HOXD10 expression level was evaluated using immunohistochemistry. 5‑Aza‑2‑deoxycytidine treatment was performed in the EC cell line Ishikawa to observe the change in HOXD10 expression levels. HOXD10 promoter methylation was more frequent in cancer samples (P<0.001). Downregulation of HOXD10 in EC samples was confirmed at the protein level using immunohistochemistry (P<0.001) and immunohistochemical staining was negatively associated with methylation status (P<0.05). Less HOXD10 protein was expressed in MEC compared with EA samples (P<0.001). The HOXD10 promoter was hypermethylated in both EA and MEC, causing decreased HOXD10 protein expression levels in EC cells. HOXD10 expression levels were partially reversed by 5‑Aza‑2‑deoxycytidine treatment. The results of the present study demonstrated that epigenetic silencing of HOXD10 putatively contributed to the tumorigenesis of EA. Although there was no significant difference in HOXD10 methylation between EA and MEC, HOXD10 protein expression levels differed between these two diseases, indicating that it may be a useful protein biomarker for distinguishing between these two lesions.

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May 2020
Volume 19 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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APA
Yang, F., Liu, D., Deng, Y., Wang, J., Mei, S., Ge, S. ... Zhang, T. (2020). Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance. Oncology Letters, 19, 3602-3608. https://doi.org/10.3892/ol.2020.11467
MLA
Yang, F., Liu, D., Deng, Y., Wang, J., Mei, S., Ge, S., Li, H., Zhang, C., Zhang, T."Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance". Oncology Letters 19.5 (2020): 3602-3608.
Chicago
Yang, F., Liu, D., Deng, Y., Wang, J., Mei, S., Ge, S., Li, H., Zhang, C., Zhang, T."Frequent promoter methylation of HOXD10 in endometrial carcinoma and its pathological significance". Oncology Letters 19, no. 5 (2020): 3602-3608. https://doi.org/10.3892/ol.2020.11467