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

Yang XH, Feng ZE, Yan M, Hanada S, Zuo H, Yang CZ, Han ZG, Guo W, Chen WT, Zhang P - PLoS ONE (2012)

Bottom Line: 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.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).XIAP is a valuable predictor of cisplatin-response and prognosis for patients with advanced head and neck cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.

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 = 0.029). 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. 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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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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pone-0031601-g004: 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).

Mentions: To investigate the casual relationship of XIAP expression and drug response of patients, we used siRNA to inhibit XIAP expression in HNSCC cell line CAL27 and WSU-HN13. Three siRNAs were designed to inhibit the expression of XIAP in CAL27 and WSU-HN13 cells, and among them, siRNA1 treatment group obtained near70% reduction of XIAP mRNA expression in both cells (Figure 3). Compared with the negative control group, cisplatin IC50 value in siRNA1 group decreased from 0.51 µg/ml to 0.20 µg/ml (P = 0.05, Figure 4) in CAL27 and from 4.32 to 1.82 µg/ml in WSU-HN13.


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

Yang XH, Feng ZE, Yan M, Hanada S, Zuo H, Yang CZ, Han ZG, Guo W, Chen WT, Zhang P - PLoS ONE (2012)

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).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3293890&req=5

pone-0031601-g004: 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).
Mentions: To investigate the casual relationship of XIAP expression and drug response of patients, we used siRNA to inhibit XIAP expression in HNSCC cell line CAL27 and WSU-HN13. Three siRNAs were designed to inhibit the expression of XIAP in CAL27 and WSU-HN13 cells, and among them, siRNA1 treatment group obtained near70% reduction of XIAP mRNA expression in both cells (Figure 3). Compared with the negative control group, cisplatin IC50 value in siRNA1 group decreased from 0.51 µg/ml to 0.20 µg/ml (P = 0.05, Figure 4) in CAL27 and from 4.32 to 1.82 µg/ml in WSU-HN13.

Bottom Line: 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.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).XIAP is a valuable predictor of cisplatin-response and prognosis for patients with advanced head and neck cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

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.

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 = 0.029). 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. 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.

Show MeSH
Related in: MedlinePlus