High-temperature-required protein A2 as a predictive marker for response to chemotherapy and prognosis in patients with high-grade serous ovarian cancers

Br J Cancer. 2015 Feb 17;112(4):739-44. doi: 10.1038/bjc.2015.1. Epub 2015 Jan 27.

Abstract

Background: High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers.

Methods: Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters.

Results: Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P<0.01). In addition, negative HtrA2 expression was identified as an independent worse prognostic factor for progression-free survival and overall survival by multivariate analyses. Furthermore, HtrA2 downregulation modulated sensitivity to platinum in serous ovarian cancer cells in vitro.

Conclusions: HtrA2 expression was a predictor for sensitivity to chemotherapy, and could be a candidate of molecular target in the treatment of high-grade serous ovarian cancers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor* / metabolism
  • Cell Line, Tumor
  • Cystadenocarcinoma, Serous / diagnosis*
  • Cystadenocarcinoma, Serous / drug therapy*
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Disease-Free Survival
  • Female
  • High-Temperature Requirement A Serine Peptidase 2
  • Humans
  • Middle Aged
  • Mitochondrial Proteins / physiology*
  • Neoplasm Grading
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Prognosis
  • Serine Endopeptidases / physiology*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Mitochondrial Proteins
  • Serine Endopeptidases
  • HTRA2 protein, human
  • High-Temperature Requirement A Serine Peptidase 2