Abstract
BackgroundApproximately 60–80% of patients with advanced head and neck squamous cell carcinoma (HNSCC) die within five years after diagnosis. Cisplatin-based chemotherapy is the most commonly used palliative treatment for these patients. To evaluate the prognostic value of X-linked inhibitor of apoptosis (XIAP) level as a potential biomarker in these patients, we investigated the relationship between XIAP expression and cisplatin response of these patients and their prognosis.Methodology/Principal FindingsSixty patients with advanced HNSCC were recruited in this study. Expression of XIAP was examined both before and after chemotherapy and was correlated with chemotherapy response, clinicopathology parameters and clinical outcomes of the patients. We found that XIAP was expressed in 17 (20.83%) of the 60 advanced HNSCC samples and the expression was significantly associated with cisplatin resistance (P = 0.036) and poor clinical outcome (P = 0.025). Cisplatin-based chemotherapy induced XIAP expression in those post-chemotherapy samples (P = 0.011), was further associated with poorer clinical outcome (P = 0.029). Multivariate analysis demonstrated that only alcohol consumption, lymph node metastasis and XIAP level were independently associated with the prognosis of advanced HNSCC patients. Inhibiting XIAP expression with siRNA in XIAP overexpressed HNSCC cells remarkably increased their sensitivity to cisplatin treatment to nearly a 3 fold difference.Conclusions/SignificanceOur results demonstrate that XIAP overexpression plays an important role in the disease course and cisplatin-resistance of advanced HNSCC. XIAP is a valuable predictor of cisplatin-response and prognosis for patients with advanced head and neck cancer. Down-regulation of XIAP might be a promising adjuvant therapy for those patients of advanced HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia [1]
Indiscriminate administration of neoadjuvant chemotherapy addresses no benefit to patients’ outcome, we found those patients who achieved a clinical response had a more favorable prognosis (p = 0.001, log-rank test), which is consistent to some previous reports [12,13]
We found a strong relationship between the expression level of X-linked inhibitor of apoptosis (XIAP) and the clinical response and prognosis of patients with advanced head and neck squamous cell carcinoma (HNSCC)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer worldwide and is the most common neoplasm in central Asia [1]. Early-stage HNSCC have high cure rates, up to 50% of patients present with advanced disease [2]. Among these advanced stage HNSCC patients, 60– 80% will die within 5 years after diagnosis [3]. In clinic only a limited number of patients benefit from cisplatin-based chemotherapy; other patients are resistant to this therapy and some will die due to treatment-related toxicity [4]. It is essential to look for predictors or potential biomarkers that may help to identify the patients who may benefit from cisplatin-based chemotherapy. 60–80% of patients with advanced head and neck squamous cell carcinoma (HNSCC) die within five years after diagnosis. Cisplatin-based chemotherapy is the most commonly used palliative treatment for these patients. To evaluate the prognostic value of X-linked inhibitor of apoptosis (XIAP) level as a potential biomarker in these patients, we investigated the relationship between XIAP expression and cisplatin response of these patients and their prognosis
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