Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status
The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow-up of 64 months. Kaplan-Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease-specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. </=10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27-5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype.
|ISBN||1097-0215 (Electronic) 1097-0215 (Linking)|
|Authors||Murphy, N. C.; Biankin, A. V.; Millar, E. K.; McNeil, C. M.; O'Toole, S. A.; Segara, D.; Crea, P.; Olayioye, M. A.; Lee, C. S.; Fox, S. B.; Morey, A. L.; Christie, M.; Musgrove, E. A.; Daly, R. J.; Lindeman, G. J.; Henshall, S. M.; Visvader, J. E.; Sutherland, R. L.;|
|Responsible Garvan Author|
|Publisher Name||INTERNATIONAL JOURNAL OF CANCER|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19676041|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10536|