title: Calpain-2 expression is associated with response to platinum based chemotherapy, progression-free and overall survival in ovarian cancer.
abstract: Ovarian cancer is routinely treated with surgery and platinum-based chemotherapy. Resistance is a major obstacle in the efficacy of this chemotherapy regimen and the ability to identify those patients at risk of developing resistance is of considerable clinical importance. The expression of calpain-1, calpain-2 and calpastatin were determined using standard immunohistochemistry on a tissue microarray of 154 primary ovarian carcinomas from patients subsequently treated with platinum-based adjuvant chemotherapy. High levels of calpain-2 expression was significantly associated with platinum resistant tumours (P = 0.031). Furthermore, high expression of calpain-2 was significantly associated with progression-free (P = 0.049) and overall survival (P = 0.006) in this cohort. The association between calpain-2 expression and overall survival remained significant in multivariate analysis accounting for tumour grade, stage, optimal debulking and platinum sensitivity (hazard ratio = 2.174; 95% confidence interval = 1.144-4.130; P = 0.018). The results suggest that determining calpain-2 expression in ovarian carcinomas may allow prognostic stratification of patients treated with surgery and platinum-based chemotherapy. The findings of this study warrant validation in a larger clinical cohort.
authors.affiliation: Academic Oncology, University of Nottingham, School of Molecular Medical Sciences, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Sabreena
authors.initials: S
authors.lastname: Safuan
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Woolston
authors.forename: Tarek
authors.initials: T
authors.lastname: Abdel-Fatah
authors.forename: Suha
authors.initials: S
authors.lastname: Deen
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Chan
authors.forename: Stewart G
authors.initials: SG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D017671:Platinum Compounds / Q000627:therapeutic use*; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies
chemical_list: D002135:Calcium-Binding Proteins; D017671:Platinum Compounds; C033668:calpastatin; D002154:Calpain; C569870:CAPN2 protein, human