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An immune-related signature that to improve prognosis prediction of breast cancer
Authors:Yi Zhang  Xuebing Di  Guoji Chen  Jiaqi Liu  Bailin Zhang  Lin Feng  Shujun Cheng  Yipeng Wang
Affiliation:1. State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China ; 2. Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Abstract:Although the classic molecular subtype of breast cancer (BRCA) has been widely used in clinical diagnosis, as a highly heterogeneous malignant tumor, the classic scheme is not enough to accurately predict the prognosis of breast cancer patients. Immune cells in the tumor microenvironment (TME) are thought to play a paramount role in tumor development and driving poor prognosis. In this study, we aimed to develop a TME-associated, immune-related signature to improve prognosis prediction of BRCA. BRCA_OURS enriched transcriptomic RNA sequencing (RNA-seq) of tumor tissue was acquired from 43 breast cancer patients before any treatment. On the immune gene profiles of 43 patients from BRCA_OURS and 932 BRCA patients from The Cancer Genome Atlas (TCGA), we identified a robust immune-related signature including one positive coefficients gene (IL-10) and other 9 genes (C14orf79, C1orf168, C1orf226, CELSR2, FABP7, FGFBP1, KLRB1, PLEKHO1, and RAC2), of which the negative coefficients suggesting higher expression were correlated with better prognosis. Based on the expression of these genes, patients were grouped into the high- and low-risk group with significant overall survival (OS) (P<0.0001). The high-risk group was likely to have inferior outcomes related to several important cancer-associated pathways, including mobilizing more Golgi vesicle-mediated transport and intensive DNA double-strand breaking, which are closely related to the infiltration of immune cells and holds the key for further growing and metastasizing. Collectively, our results highlight that the immunological value within BRCA is an essential determinant of prognostic factor. Our signature may provide an effective risk stratification tool for clinical prognosis assessment of patients with BRCA.
Keywords:Breast cancer   RNA-seq   immune-related signature   tumor microenvironment
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