title: DJ-1 protein expression as a predictor of pathological complete remission after neoadjuvant chemotherapy in breast cancer patients.
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.
authors.affiliation: Department of Basic Pathology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Kawate
authors.forename: Keiichi
authors.initials: K
authors.lastname: Iwaya
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaise
authors.forename: Miki
authors.initials: M
authors.lastname: Oda
authors.forename: Eiichi
authors.initials: E
authors.lastname: Sato
authors.forename: Sadayuki
authors.initials: S
authors.lastname: Hiroi
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsubara
authors.forename: Norio
authors.initials: N
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015513:Oncogene Proteins / Q000032:analysis / Q000096:biosynthesis*; D000071617:Protein Deglycase DJ-1; D012074:Remission Induction
chemical_list: D014408:Biomarkers, Tumor; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1