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. 2012;7(3):e31601.
doi: 10.1371/journal.pone.0031601. Epub 2012 Mar 5.

XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer

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XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer

Xi-Hu Yang et al. PLoS One. 2012.

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 VSports手机版. 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 findings: 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 V体育安卓版. 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/significance: Our results demonstrate that XIAP overexpression plays an important role in the disease course and cisplatin-resistance of advanced HNSCC V体育ios版. 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. .

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Immunohistochemical staining of XIAP in advanced HNSCC (×400).
A: Negative control with PBS instead of first antibody; B: Low expression of XIAP(the percentage of positive rate <25%); C: High expression of XIAP(the percentage of positive rate >25%).
Figure 2
Figure 2. Overall survival.
A: Overall survival rate by XIAP scores. Patients whose tumors expressed high levels of XIAP generally had a poorer prognosis than those patients whose tumors expressed low levels of XIAP in pre-chemotherapy cancer tissue; B: Overall survival rate by chemoresponse. Patients whose tumors were responsive to chemotherapy generally had a better prognosis than those patients whose tumor was resistant to chemotherapy; C: XIAP scores of post-chemotherapy samples. XIAP levels in post-chemotherapy samples were also significantly related to the patient overall survival rates.
Figure 3
Figure 3. XIAP expression inhibited by siRNA.
Inhibition efficacy of siRNA-1, siRNA-2 and siRNA-3 on the expression of XIAP mRNA was examined in CAL27 cell (Upper) and WSU-HN13 cell (Lower) with Real-time PCR. XIAP siRNA1 treatment group obtained near 70% reduction of XIAP mRNA expression in both cells.
Figure 4
Figure 4. Inhibiting XIAP expression sensitized both CAL27and WSU-HN13 to cisplatin treatment.
XIAP siRNA-1 effectively inhibited the expression of XIAP protein in both CAL27 and WSU-HN13 cells (Upper) and decreased the cisplatin IC50 value from 0.51 µg/ml to 0.20 µg/ml in CAL27 and from 4.32 to 1.82 µg/ml in WSU-HN13 (Lower).

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