Fifteen genes were selected as hub genes because of high degrees, among which, low expression of four genes was associated with worse OS of patients with BC, including RPS9, RPL11, RPS14 and RPL10A. Additionally, the small molecular agent emetine may be a potential drug for BC.

The BMP2, PPARG and PRKAR2B genes may therefore be potential biomarkers in the treatment of PCa. Additionally, the small molecular agent phenoxybenzamine may be a potential drug for PCa.

Abstract:The tumor microenvironment is composed of numerous cell types, including tumor, immune and stromal cells. Cancer cells interact with the tumor microenvironment to suppress anticancer immunity. In this study, we molecularly dissected the tumor microenvironment of breast cancer was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/368605 doi: bioRxiv preprint first posted online Jul. 13, 2018; 3 Breast cancer is the most common cancer and the leading cause of death from cancer in women worldwide(1). Four subtypes of breast cancer with distinct expression profiles have been classified based on gene expression signatures associated with highly variable clinical characteristics(2, 3).To design targeted treatment for such a diverse disease, understanding its molecular mechanism of initiation and progression is essential(4). Several studies have shown that the presence of tumor-5 infiltrating lymphocytes (TILs) is associated with breast cancer progression and neoadjuvant chemotherapy response(5-7). TIL levels within and between different subtypes of breast cancer vary(8). Based on the CD8 + T cell infiltration phenotype, tumors can be categorized as T-cellinflamed and non-T-cell-inflamed tumors(9). In T-cell-inflamed tumors, the tumor cells act together with the tumor microenvironment (TME) to inhibit the antitumor functions of T cells. 10This process results in an exhausted T cell phenotype. Non-T-cell-inflamed tumors escape immune system clearance by preventing T cell infiltration into the TME(10). Cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and oncogenic pathway alterations in tumor cells are reportedly responsible for the non-T-cell-inflamed phenotype(10-14). However, the mechanism of immune evasion in breast cancer remains unclear. A recent study showed that a 15 high number of TILs was beneficial for triple negative breast cancer (TNBC) and HER-2-positive breast cancer patient survival, but this parameter was an adverse prognostic factor for luminal HER2-negative breast cancer patient survival(15). High-resolution mapping of the TME composition and cell states of different breast cancer subtypes will help us understand the different effects of TILs and the mechanism of tumor immune evasion in breast cancer. 20In the past five years, the development of high-throughput single-cell RNA sequencing has enabled high-resolution studies of biological processes(16). Single-cell transcriptome profiling of tumor cells has been used to characterize heterogeneous tumor cells and tumor-associated stromal All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/368605 doi: bioRxiv preprint first posted online Jul. 13, 2018; 4 and immune cells (17)(18)(19). To un...

Currently, over 20 genes have been defined that can confer susceptibility for high-risk breast cancer.Although research has proved the utility of multiple-gene sequencing in the assessment of breast cancer risk, there is little data from China patients. Here, we use a multiple-gene sequencing panel to identify the variant spectrum in Chinese high-risk breast cancer subjects.A total of 829 Chinese high-risk breast cancer patients participated in the research. The coding regions of 115 hereditary cancer susceptibility genes were sequenced using a next generation sequencing platform.In total, 193 pathogenic variants were identified in 45 genes from 177 patients. The pathogenic variant carrier rate is 21.4%: with 10.5% patients carrying a BRCA1 or BRCA2 mutation only, 10.0% of patients carried non-BRCA gene mutations only, while 1.0% of patients carried both a BRCA1/2 and a non-BRCA gene mutation. Variants of uncertain significance (VUS) totaling 2632 were identified in 115 genes from 787 of 829 patients: 82.5% patients carried more than one VUS, and only 5.1% patients did not carry any VUS. Families carrying pathogenic variants were tracked and adenoma was founded in three of them.Our data provide a comprehensive analysis of potential susceptibility variations of high-risk for breast cancer in a Chinese population. This data will be useful for the comparison of the susceptibility variation spectrum between different populations and to discover potential pathogenic variants to improve the prevention and treatment of high-risk breast cancer.