Abstract | BACKGROUND: X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti-apoptotic proteins leading to chemoresistance in several cancers. The aim of this study is to evaluate the impact of XIAP expression upon ovarian clear cell carcinoma (CCC) that has a platinum-resistant phenotype. METHODS: Tissue microarrays made from 90 CCC patients were analysed for immunohistochemical expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines were evaluated whether XIAP silencing could modulate sensitivity to platinum agent in vitro. RESULTS: High XIAP expression was observed in 30 (33%) of 90 CCC cases, and was associated with c-Met (<0.01) and Bcl-XL (<0.01) expression. Cases with high XIAP expression had lower response rate to primary platinum-based chemotherapy (10% vs 65%, P=0.02). In stages II-IV tumours, high XIAP expression was related with worse progression-free survival (PFS, P=0.02). Furthermore, high XIAP expression was identified as an independent worse prognostic factor for PFS and overall survival. Finally, downregulation of XIAP using XIAP-specific small interfering RNA increased sensitivity to cisplatin in human cancer cells derived from CCC. CONCLUSIONS: X-chromosome-linked inhibitor of apoptosis expression was correlated with chemoresistance of primary chemotherapy, and identified as a prognostic marker for CCC. X-chromosome-linked inhibitor of apoptosis could be a candidate for new therapeutic target in CCC.
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Authors | M Miyamoto, M Takano, K Iwaya, N Shinomiya, M Kato, T Aoyama, N Sasaki, T Goto, A Suzuki, J Hitrata, K Furuya |
Journal | British journal of cancer
(Br J Cancer)
Vol. 110
Issue 12
Pg. 2881-6
(Jun 10 2014)
ISSN: 1532-1827 [Electronic] England |
PMID | 24853184
(Publication Type: Journal Article)
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Chemical References |
- Antineoplastic Agents
- BCL2L1 protein, human
- Biomarkers, Tumor
- RNA, Small Interfering
- X-Linked Inhibitor of Apoptosis Protein
- bcl-X Protein
- Proto-Oncogene Proteins c-met
- Cisplatin
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Topics |
- Adenocarcinoma, Clear Cell
(drug therapy, genetics, mortality)
- Adult
- Aged
- Antineoplastic Agents
(therapeutic use)
- Biomarkers, Tumor
(genetics)
- Cell Line, Tumor
- Cell Proliferation
- Cisplatin
(therapeutic use)
- Disease-Free Survival
- Down-Regulation
- Drug Resistance, Neoplasm
(genetics)
- Female
- Humans
- Middle Aged
- Ovarian Neoplasms
(drug therapy, genetics, mortality)
- Proto-Oncogene Proteins c-met
(biosynthesis)
- RNA Interference
- RNA, Small Interfering
- X-Linked Inhibitor of Apoptosis Protein
(biosynthesis, genetics)
- bcl-X Protein
(biosynthesis)
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