Two New Stromal Signatures Stratify Breast Cancers with Different Prognosis
Xiangqian Guo, Shirley X Zhu, Kelli Montgomery, Matt van de Rijn, Robert B West. Stanford University School of Medicine, Stanford, CA
Background: Carcinoma is comprised of malignant epithelial cells and the tumor microenvironment. Although the initiation and progression of carcinoma involves the acquisition of mutations and the dysregulation of gene expression in the neoplastic epithelia cells, results over the last couple of decades has showed that the microenvironment plays an important role in the initiation, progression and metastasis of cancer. Our group previously identified stromal gene expression signatures associated with outcome differences in breast cancer using gene expression microarrays.
Design: In order to find new types of tumor stroma gene expression patterns, we have gene expression profiled 10 types of different fibrous tumors. Because these are uncommon tumors not typically fresh frozen, we used a modified RNA-seq protocol that we developed, 3'end sequencing (3SEQ), to identify different fibrous tumor specific gene expression signatures.
Results: 53 fibrous tumors representing 10 groups of benign fibrous tumors were expression profiled, and an average of 29 million reads were generated for each sample. Only the elastofibromatosis (EF) and fibromatosis of tendon sheath (FOTS) gene signatures demonstrated robust outcome results for survival in the four breast cancer datasets. The EF signature positive breast cancers (20-33%) demonstrated significantly better outcome for survival. In contrast, the FOTS signature positive breast cancers (11-35%) had a worse outcome. While the EF and FOTS signatures shared some assigned breast cancer cases with two previously identified stromal signatures (DTF fibroblast and CSF1 macrophage signatures), they were statistically independent signatures in three of the four data sets. EF+ breast cancers showed best outcome in survival independent of whether the breast cancer is DTF+ or DTF-. The EF+/DTF+ breast cancers were significantly more likely to be ER positive, PR positive, low grade, p53 wild type than EF-/DTF- breast cancers. FOTS+/CSF1- breast cancer showed the worst outcome in survival. FOTS+/CSF1+ breast cancers were significantly more likely to be ER negative, PR negative, Grade 3, p53 mutant than FOTS-/CSF1- breast cancers.
Conclusions: Over all, we defined and validated two new stromal signatures in breast cancer (EF and FOTS), which showed robust prognosis indication in breast cancer. The combined stromal signatures of EF, FOTS, DTF fibroblast, and CSF1 macrophage identifies between 74%-90% of all breast cancers.
Category: Special Category - Pan-genomic/Pan-proteomic approaches to Cancer
Tuesday, March 5, 2013 9:30 AM
Poster Session III # 234, Tuesday Morning