NM23-H1 expression of head and neck squamous cell carcinoma in association with the response to cisplatin treatment

Abstract

// Yi-Fen Wang 1,2 , Chun-Ju Chang 3 , Jen-Hwey Chiu 4 , Chin-Ping Lin 5 , Wing-Yin Li 2,6 , Shyue-Yih Chang 1 , Pen-Yuan Chu 1,2 , Shyh-Kuan Tai 1,2 , Yu-Jen Chen 4,5,7 1 Department of Otorhinolaryngology and Head and Neck Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 2 Department of Medicine, National Yang Ming University, Taipei, Taiwan 3 Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan 4 Institute of Traditional Medicine, National Yang Ming University, Taipei, Taiwan 5 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan 6 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan 7 Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan Correspondence: Chun-Ju Chang, email: // Yu-Jen Chen,, email: // Keywords : Head and neck squamous cell carcinoma (HNSCC); NM23-H1; Metastasis; Cisplatin; Prognosis Received : February 20, 2014 Accepted : April 16, 2014 Published : April 18, 2014 Abstract We recently reported that low NM23-H1 expression of head and neck squamous cell carcinoma (HNSCC) correlated with poor patients’ prognosis. Growing evidence has indicated that high tumor NM23-H1 expression contributes to a good response to chemotherapy. Therefore, we investigated the role of NM23-H1 in susceptibility of HNSCC cells to cisplatin and its clinical significance, as well as the in vitro study for validation was performed. Using immunohistochemistry, we analyzed NM23-H1 expression in surgical specimens from 46 HNSCC patients with cervical metastases receiving surgery and adjuvant chemoradiotherapy. Low tumor NM23-H1 expression correlated with locoregional recurrence of HNSCC following postoperative cisplatin-based therapy (p = 0.056) and poor patient prognosis (p = 0.001). To validate the clinical observation and the effect of NM23-H1 on cisplatin cytotoxicity, we established several stable clones derived from a human HNSCC cell line (SAS) by knockdown and overexpression. Knockdown of NM23-H1 attenuated the chemosensitivity of SAS cells to cisplatin, which was associated with reduced cisplatin-induced S-phase accumulation and downregulation of cyclin E1 and A. Overexpression of NM23-H1 reversed these results, indicating the essential role of NM23-H1 in treatment response to cisplatin. NM23-H1 may participate in HNSCC cell responses to cisplatin and be considered a potential therapeutic target.