Dataset for: PROGNOSTIC AND FUNCTIONAL ROLE OF SUBTYPE-SPECIFIC TUMOR-STROMA INTERACTION IN BREAST CANCER
2017-08-23T04:33:00Z (GMT) by
None of the clinically relevant gene expression signatures available for breast cancer were specifically developed to capture the influence of the microenvironment on tumor cells. Here, we attempted to build subtype-specific signatures derived from an in vitro model reproducing tumor cell modifications after interaction with activated or normal stromal cells. Gene expression signatures derived from HER2+, luminal and basal breast cancer cell lines (treated by normal fibroblasts or cancer-associated fibroblasts conditioned media) were evaluated in clinical tumors by in silico analysis on published gene expression profiles (GEPs). Patients were classified as microenvironment-positive (µENV+ve), i.e with tumors showing molecular profiles suggesting activation by the stroma, or negative (µENV-ve) based on correlation of their tumors’ GEP with the respective subtype-specific signature. Patients with estrogen receptor alpha (ER)+/HER2-/µENV+ve tumors were characterized by 2.5-fold higher risk of developing distant metastases (HR= 2.546; 95% Cl: 1.751-3.701, P=9.84E-07), while µENV status did not affect, or only suggested the risk of distant metastases, in women with HER2+ (HR=1.541; 95% Cl: 0.788-3.012, P=0.206) or ER-/HER2- tumors (HR=1.894; 95% Cl: 0.938-3.824; P=0.0747), respectively. In ER+/HER2- tumors, the µENV status remained significantly associated with metastatic progression (HR=2.098; CI: 1.214-3.624; P=0.00791) in multivariable analysis including size, age and genomic grade index. Validity of our in vitro model was also supported by in vitro biological endpoints such as cell growth (MTT-assay) and migration/invasion (Transwell-assay). In vitro-derived gene signatures tracing the bidirectional interaction with cancer activated fibroblasts is subtype-specific and adds independent prognostic information to classical prognostic variables in women with ER+/HER2- tumors.