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

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

doi:10.18632/oncotarget.1912

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.

Highlights

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant pathology, with an incidence ranging from 40% worldwide [1, 2]
To clarify the role of NM23-H1 in the prognosis of HNSCC patients with resectable metastases treated by postoperative cisplatin, we examined NM23-H1 expression in the surgical tumor specimens
In patients with cervical metastases receiving postoperative cisplatin-based chemoradiation, low NM23-H1 expression in HNSCC tumors correlated with locoregional recurrence, further indicative of poor prognosis

Summary

Introduction

Head and neck squamous cell carcinoma (HNSCC) is the most common malignant pathology, with an incidence ranging from 40% worldwide [1, 2]. In Taiwan, HNSCC has been the fourth or fifth leading cause of cancer death in the men the seventh among the entire population since 1991 [3]. Despite the use of multiple therapeutic modalities, the overall survival of HNSCC patients has not improved in the last two decades [4]. One major cause of treatment failure is early metastases and poor response of HNSCC cells to chemoradiation. Clinical surveys showed that more than half of HNSCC patients with resectable tumors had lymphatic metastases at diagnosis [5, 6]. Biomarkers for predicting the response to anticancer agents are imperative to initiate optimal treatments and improve therapeutic outcomes

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Conclusion