title: XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer.
abstract: BACKGROUND
  Approximately 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.
  
  
  RESULTS
  Sixty 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
  Our 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xi-Hu
authors.initials: XH
authors.lastname: Yang
authors.forename: Zhi-En
authors.initials: ZE
authors.lastname: Feng
authors.forename: Ming
authors.initials: M
authors.lastname: Yan
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hanada
authors.forename: Hui
authors.initials: H
authors.lastname: Zuo
authors.forename: Cheng-Zhe
authors.initials: CZ
authors.lastname: Yang
authors.forename: Ze-Guan
authors.initials: ZG
authors.lastname: Han
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Wan-Tao
authors.initials: WT
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051636:X-Linked Inhibitor of Apoptosis Protein; D002945:Cisplatin