DJ-1 protein expression as a predictor of pathological complete remission after neoadjuvant chemotherapy in breast cancer patients

Breast Cancer Res Treat. 2013 May;139(1):51-9. doi: 10.1007/s10549-013-2523-0. Epub 2013 Apr 17.

Abstract

Parkinson's disease is associated with DJ-1/Parkinson protein 7 dysfunction. In contrast, hyperactivity of DJ-1 increases the resistance of cancer cells to apoptosis. Recent genetic studies showed that, in addition to apoptosis pathways, DJ-1 is also involved in cellular defense against reactive oxygen species. The activity of apoptotic and cellular defense pathways is key in determining drug sensitivity. DJ-1 overexpression is associated with various cancers. However, we previously found that there were approximately 50 % patients with breast cancers that expressed low levels of DJ-1 protein, despite mRNA upregulation. Furthermore, low DJ-1 expression was a significant predictor of poor clinical outcome in these patients. This study aimed to determine the association between low DJ-1 protein expression and pathological complete remission (pCR) after neoadjuvant chemotherapy in breast cancer patients. Expression of DJ-1 in pre-therapeutic needle biopsies and surgical specimens obtained from 205 breast cancer cases that received neoadjuvant chemotherapy was determined using immunohistochemistry and in situ hybridization. Chemotherapy comprised epirubicin/cyclophosphamide taxane-based regimens with or without the inclusion of trastuzumab. Univariate and multivariate analyses were used to evaluate the predictive value of DJ-1 on pCR. Low DJ-1 protein expression was detected in 45.3 % (93/205) of all breast cancer cases and in 79.6 % (39/49) of pCR cases, irrespective of maintained mRNA levels. DJ-1 expression [hazard ratio (HR): 1.36; 95 % confidence interval (CI): 1.01-1.84] and HER2 status (HR: 0.84; 95 % CI: 0.62-1.14), in contrast to histological grade, hormone receptors status, Ki-67 labeling index, and intrinsic subtype, were significant predictors of pCR. Low DJ-1 expression predicted pCR in luminal A (P = 0.0004), luminal B (P = 0.0194), and triple negative (P = 0.0143) subtypes breast cancer patients and in patients receiving additional trastuzumab treatment (P = 0.008). In conclusion, low DJ-1 protein expression is a significant predictor of pCR after neoadjuvant chemotherapy in breast cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / biosynthesis*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Oncogene Proteins / analysis
  • Oncogene Proteins / biosynthesis*
  • Protein Deglycase DJ-1
  • Remission Induction

Substances

  • Biomarkers, Tumor
  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • PARK7 protein, human
  • Protein Deglycase DJ-1