Comprehensive profiling of biological processes reveals two major prognostic subtypes in breast cancer
Heterogeneity is the major obstacle to breast cancer target therapy. Classification of breast cancer with significant biological process may reduce the influence of heterogeneity of intrinsic tumor. We used survival analysis to filter 95 gene sets and classify 638 breast cancer samples into two subtypes based on those gene sets associated with prognosis. Clinical outcome of two subtypes were evaluated with disease-free survival, distant metastasis-free survival, and overall survival levels in three databases and ER+, PR+ HER2+, and TNBC groups. We established a novel classification with 95 prognostic gene sets. In the training and validation cohorts, the subtype 1 was characterized by significant gene sets associated with regulation of metabolic process and enzyme activity and predicted obviously improved clinical outcome than subtype 2, which was enriched by tumor cell division, mitosis, and cell cycle-related gene sets (P < 0.05). When evaluated prognostic impact of subtypes in ER+, PR+ HER2+, and TNBC groups, we found that patients in subtype 1 showed better prognosis in ER+ and PR+ groups (P < 0.05) but had no difference from prognosis of subtype 2 in HER2+ and TNBC groups. These findings may have implications in understanding of breast cancer and filtering effective therapeutic strategies for targeted therapy.
KeywordsBiological process Breast cancer Prognosis Subtypes Targeted therapy
This work was supported by the National Natural Science Foundation of China (81402172) and The Jiangsu Province Natural Science Foundation of China (BK20130074)
Fei Chen, Sheng Gao, and Hong Yin designed the study. Fengliang Wang, Jingjing Ma, Min Zhang, Mingming Lv, and Qian Zhou analyzed the data. Ziyi Fu, Cheng Lu, and Hong Yin conducted the statistical analysis. Hong Yin wrote the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standard
Conflicts of interest
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