Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer

Br J Cancer. 2015 Apr 14;112(8):1332-9. doi: 10.1038/bjc.2015.114. Epub 2015 Mar 31.

Abstract

Background: Phosphoglycerate kinase-1 (PGK1) has been recently documented in various malignancies; however, the molecular mechanisms of the variable PGK1 expression and its clinical significance in terms of survival status remain unclear.

Methods: Real-time quantitative PCR (real-time qPCR) and western blotting were used to verify PGK1 expression in 46 fresh breast cancer tissues and matched normal tissues. A tissue microarray (TMA) comprising 401 breast cancer tissues and 123 matched normal tissues was investigated by immunohistochemistry for PGK1 expression. Then, the correlation between PGK1 expression and the clinicopathologic features was analysed.

Results: PGK1 mRNA and protein expression were significantly increased in breast cancer tissues compared with that in normal breast tissues. High PGK1 expression was significantly associated with higher histologic grade (P=0.009) and positive status of ER (P=0.004), Her-2 (P=0.026) and P53 (P=0.012). High levels of PGK1 expression were associated with worse overall survival (OS, P=0.02). Furthermore, patients who underwent paclitaxel chemotherapy with high levels PGK1 expression had shorter OS than did those with low levels of PGK1 expression (P<0.001). Multivariate analysis indicated that PGK1 (P=0.001) was an independent predictor in the patients treated with paclitaxel.

Conclusions: PGK1 is a prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Drug Resistance, Neoplasm*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Paclitaxel / therapeutic use
  • Phosphoglycerate Kinase / genetics*
  • Phosphoglycerate Kinase / metabolism*
  • Prognosis

Substances

  • Antineoplastic Agents, Phytogenic
  • Biomarkers, Tumor
  • PGK1 protein, human
  • Phosphoglycerate Kinase
  • Paclitaxel