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An immune-related signature that to improve prognosis prediction of breast cancer

机译:改善乳腺癌预后预测的免疫相关签名

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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) (P0.0001). 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.
机译:虽然乳腺癌(BRCA)的经典分子亚型已被广泛用于临床诊断,但作为高度异质的恶性肿瘤,经典方案不足以准确预测乳腺癌患者的预后。肿瘤微环境(TME)中的免疫细胞被认为在肿瘤发育中发挥至高无程度的作用,推动预后差。在这项研究中,我们旨在开发一种TME相关的免疫相关签名,以改善BRCA的预后预测。在任何治疗前,从43名乳腺癌患者中获得肿瘤组织的转发组织RNA测序(RNA-SEQ)的BRCA_URS浓缩(RNA-SEQ)。在来自BRCA_OURS的43名患者的免疫基因谱和来自癌症基因组ATLAS(TCGA)的932例BRCA患者,我们鉴定了一种稳健的免疫相关签名,包括一个正系数基因(IL-10)和其他9基因(C14ORF79,C1ORF168, C1ORF226,CELSR2,FABP7,FGFBP1,KLRB1,PLEKHO1和RAC2),其中构成更高表达的负系数与更好的预后相关。基于这些基因的表达,将患者分组为具有显着整体存活(OS)的高风险组(OS)(P <0.0001)。高风险组可能具有与几种重要癌症相关途径相关的劣质结果,包括动员更多的高尔基囊泡介导的运输和密集型DNA双链破裂,这与免疫细胞渗透密切相关并占据关键进一步增长和转移。集体,我们的结果强调BRCA中的免疫价值是预后因素的基本决定因素。我们的签名可以提供有效的风险分层工具,用于BRCA患者的临床预后评估。

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