NM23-H1 Expression of Head and Neck Squamous Cell Carcinoma in Association With the Response to Irradiation

Yi-Fen Wang; Yi-Ke Lin; Chin-Ping Lin; Yu-Jen Chen; Chun-Ju Chang

doi:10.3389/fonc.2021.646167

NM23-H1 Expression of Head and Neck Squamous Cell Carcinoma in Association With the Response to Irradiation

Front Oncol. 2021 Mar 30:11:646167. doi: 10.3389/fonc.2021.646167. eCollection 2021.

Authors

Yi-Fen Wang^{1

2}, Yi-Ke Lin^{1

3}, Chin-Ping Lin⁴, Yu-Jen Chen^{4

5

6

7

8}, Chun-Ju Chang³

Affiliations

¹ Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.
² Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
³ Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan.
⁴ Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
⁵ Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan.
⁶ Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan.
⁷ Department of Nursing, MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.
⁸ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.

Abstract

A low NM23-H1 expression in head and neck squamous cell carcinoma (HNSCC) was found to be associated with poor clinical outcome. Therefore, we investigated the role of NM23-H1 in the susceptibility of HNSCC cells to irradiation and its clinical significance. An in vitro study was also conducted to validate the results. Furthermore, we used immunohistochemistry to analyze NM23-H1 expression found in specimens of 50 HNSCC patients with cervical metastases receiving postoperative radiotherapy. Low tumor NM23-H1 expression was associated with locoregional recurrence of HNSCC (p=0.040; Hazard ratio=5.62) and poor clinical outcome (p=0.001; Hazard ratio=4.90). To confirm the effect of NM23-H1 on radiation-induced cytotoxicity, we generated several stable clones derived from a human HNSCC cell line (SAS) using knockdown and overexpression of NM23-H1. Knockdown of NM23-H1 decreased the radio-sensitivity of SAS cells, possibly associated with a decrease in the radiation-induced G2/M-phase accumulation and upregulation of cyclin B1. On the contrary, overexpression of NM23-H1 can reverse the aforementioned adverse results. Consequently, we suggest that NM23-H1 expression may be considered as a potential therapeutic treatment option for HNSCC patients.

Keywords: Head and neck squamous cell carcinoma; NM23-H1; clinical outcome; metastasis; radiation.