Oncotarget

Research Papers:

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

Yi-Fen Wang, Chun-Ju Chang _, Jen-Hwey Chiu, Chin-Ping Lin, Wing-Yin Li, Shyue-Yih Chang, Pen-Yuan Chu, Shyh-Kuan Tai and Yu-Jen Chen

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Oncotarget. 2014; 5:7392-7405. https://doi.org/10.18632/oncotarget.1912

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Abstract

Yi-Fen Wang1,2, Chun-Ju Chang3, Jen-Hwey Chiu4, Chin-Ping Lin5, Wing-Yin Li2,6, Shyue-Yih Chang1, Pen-Yuan Chu1,2, Shyh-Kuan Tai1,2, Yu-Jen Chen4,5,7

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.


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