Abstract 3393: Identification of genes mediating early dissemination of tumor cells in breast cancer

The presence of disseminated tumor cells in bone marrow (BM) at primary breast cancer diagnosis is an independent prognostic factor. We have recently shown that there is a specific gene expression signature associated with BM micrometastasis in lung cancer patients (Wrage et al., CCR 2009). Our aim was therefore, to assess whether early metastatic spread of breast tumor cells into BM is also associated with a specific genetic signature. The gene expression profiles of primary early stage breast cancer patients (T1-2, N0, M0) with (n=15) and without (n=15) early tumor cell dissemination into BM were analyzed using the Affymetrix GeneChip platform. The BM status was assessed by immunostaining the BM samples with anti-cytokeratin antibody A45-B/B3. Gene expression data were normalized using gcrma and customized chip description files were used to re-map all probes to ENSEMBL transcripts. Rank sum test analysis was used to obtain transcripts that were significantly differentially expressed between BM positive and BM negative patients. Five publicly available breast cancer and three lung cancer expression data sets were used to correlate the findings with survival information. When using false discovery rate of 0.2 and a p-value The five large breast cancer data sets consisting of 1621 patients in total were used for in silico validations. Among the down-regulated genes 17 showed a significant association with survival in at least one data set, whereas 6 genes showed an association in at least two data sets. Among the four up-regulated genes a high expression of one gene was associated with shorter survival in two data sets whereas another gene was associated with shorter survival in one data set. In summary, we could identify a set of potential key regulators of early hematogeneous spread of tumor cells. These potential new targets might be used to prevent metastatic relapse by eliminating DTC before the occurrence of overt metastases. Some of the identified genes are supposed to play a role only for the early steps of the metastatic cascade, i.e. dissemination, whereas others were shown also to be important for metastatic out-growth in distant organs and thus having a high impact on the survival of a patient. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3393.