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X-chromosome-linked inhibitor of apoptosis as a key factor for chemoresistance in clear cell carcinoma of the ovary.

AbstractBACKGROUND:
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.
AuthorsM Miyamoto, M Takano, K Iwaya, N Shinomiya, M Kato, T Aoyama, N Sasaki, T Goto, A Suzuki, J Hitrata, K Furuya
JournalBritish journal of cancer (Br J Cancer) Vol. 110 Issue 12 Pg. 2881-6 (Jun 10 2014) ISSN: 1532-1827 [Electronic] England
PMID24853184 (Publication Type: Journal Article)
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
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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