A specific gene expression signature for visceral organ metastasis in breast cancer

Background: Visceral organ metastasis is associated with poor survival outcomes in terms of metastasis free- and overall survival in breast carcinomas. Identification of a gene expression profile in tumours that selects a subpopulation of patients that is more likely to develop visceral organ metastases will help elucidate mechanisms for the development of distant metastases and could be of clinical value. With this study we aimed to determine genomic predictors that would help to distinguish breast cancer patients with more likelihood to develop visceral metastasis. Methods: Gene expression profiling data of 157 primary tumours from breast cancer patients who developed distant metastases were analyzed and differentially expressed genes between the group of tumours with visceral metastasis and the those without visceral metastases were identified. Published data were used to validate our findings. Multivariate logistic regression tests were applied to further investigate the association between the gene-expression-signature and clinical variables. Survival analyses were performed by the Kaplan-Meier method. Results: Fourteen differentially expressed genes (WDR6, CDYL, ATP6V0A4, CHAD, IDUA, MYL5, PREP, RTN4IP1, BTG2, TPRG1, ABHD14A, KIF18A, S100PBP and BEND3) were identified between the group of tumours with and without visceral metastatic disease. Five of these genes (CDYL, ATP6V0A4, PREP, RTN4IP1 and KIF18A) were up-regulated and the other genes were down-regulated. This gene expression signature was validated in the training and in the independent data set (p 2.13e- 08 and p 9.68e- 06, respectively). Multivariate analyses revealed that the 14-gene-expression-signature was associated with visceral metastatic disease (p 0.001, 95% CI 1.43-4.27), independent of other clinicopathologic features. This signature has been also found to be associated with survival status of the patients (p <.001). Conclusion: We have identified an unique gene expression signature which is specific to visceral metastasis. This 14-gene-expression-signature may play a role in identifying the subgroup of patients with potential to develop visceral metastasis.