Two New Stromal Signatures Stratify Breast Cancers with Different Prognosis

Purpose: Multiple studies from last decades have shown that the microenvironment of carcinomas plays an important role in the initiation, progression and metastasis of cancer. Our group has previously identified novel cancer stroma gene expression signatures associated with outcome differences in breast cancer by gene expression profiling of two tumors of fibroblasts as surrogates for physiologic stromal expression patterns. The aim of this study is to find additional new types of tumor stroma gene expression patterns. Results: 53 tumors were sequenced by 3SEQ with an average of 29 million reads per sample. Both the elastofibroma (EF) and fibroma 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% of the cohort) demonstrated significantly better outcome for survival. In contrast, the FOTS signature positive breast cancers (11-35% of the cohort) had a worse outcome. The combined stromal signatures of EF, FOTS, and our previously identified DTF, and CSF1 signatures characterize, in part, the stromal expression profile for the tumor microenvironment for between 74%-90% of all breast cancers. Conclusions: We defined and validated two new stromal signatures in breast cancer (EF and FOTS), which are significantly associated with prognosis. Overall design: Gene expression profiling by 3SEQ was performed on 8 additional types of fibrous tumors, to identify different fibrous tumor specific gene expression signatures. We then determined the significance of the fibrous tumor gene signatures in four publically available breast cancer datasets (GSE1456, GSE4922, GSE3494, NKI Dataset).

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Guo X, Zhu SX, Brunner AL, van de Rijn M, West RB