Stathmin protein level, a potential predictive marker for taxane treatment response in endometrial cancer

PLoS One. 2014 Feb 25;9(2):e90141. doi: 10.1371/journal.pone.0090141. eCollection 2014.

Abstract

Stathmin is a prognostic marker in many cancers, including endometrial cancer. Preclinical studies, predominantly in breast cancer, have suggested that stathmin may additionally be a predictive marker for response to paclitaxel. We first evaluated the response to paclitaxel in endometrial cancer cell lines before and after stathmin knock-down. Subsequently we investigated the clinical response to paclitaxel containing chemotherapy in metastatic endometrial cancer in relation to stathmin protein level in tumors. Stathmin level was also determined in metastatic lesions, analyzing changes in biomarker status on disease progression. Knock-down of stathmin improved sensitivity to paclitaxel in endometrial carcinoma cell lines with both naturally higher and lower sensitivity to paclitaxel. In clinical samples, high stathmin level was demonstrated to be associated with poor response to paclitaxel containing chemotherapy and to reduced disease specific survival only in patients treated with such combination. Stathmin level increased significantly from primary to metastatic lesions. This study suggests, supported by both preclinical and clinical data, that stathmin could be a predictive biomarker for response to paclitaxel treatment in endometrial cancer. Re-assessment of stathmin level in metastatic lesions prior to treatment start may be relevant. Also, validation in a randomized clinical trial will be important.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / deficiency
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Bridged-Ring Compounds / pharmacology*
  • Bridged-Ring Compounds / therapeutic use
  • Cell Line, Tumor
  • Endometrial Neoplasms / drug therapy*
  • Endometrial Neoplasms / metabolism*
  • Endometrial Neoplasms / pathology
  • Female
  • Gene Knockdown Techniques
  • Humans
  • Neoplasm Metastasis
  • Paclitaxel / pharmacology
  • Paclitaxel / therapeutic use
  • Stathmin / deficiency
  • Stathmin / genetics
  • Stathmin / metabolism*
  • Taxoids / pharmacology*
  • Taxoids / therapeutic use
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Stathmin
  • Taxoids
  • taxane
  • Paclitaxel

Grants and funding

Helse Vest, Research Council of Norway (803100, 805797) and The Norwegian Cancer Society (Harald Andersens legat) supported this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.