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识别预测腔 A 型浸润性小叶乳腺癌生存的 5 基因风险评分模型。

Identification of a 5-gene-risk score model for predicting luminal A-invasive lobular breast cancer survival.

机构信息

Department of Ultrasound in Obstetrics and Gynecology, The Second Affiliated Hospital of Shantou University Medical College, Shantou, 515041, Guangdong, China.

Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou University Medical College, No.69 North Dongxia Road, Shantou, 515041, Guangdong, China.

出版信息

Genetica. 2022 Oct;150(5):299-316. doi: 10.1007/s10709-022-00157-7. Epub 2022 May 10.

Abstract

Breast cancer is a devastating malignancy, among which the luminal A (LumA) breast cancer is the most common subtype. In the present study, we used a comprehensive bioinformatics approach in the hope of identifying novel prognostic biomarkers for LumA breast cancer patients. Transcriptomic profiling of 611 LumA breast cancer patients was downloaded from TCGA database. Differentially expressed genes (DEGs) between tumor samples and controls were first identified by differential expression analysis, before being used for the weighted gene co-expression network analysis. The subsequent univariate Cox regression and LASSO algorithm were used to uncover key prognostic genes for constructing multivariate Cox regression model. Patients were stratified into high-risk and low-risk groups according to the risk score, and subjected to multiple downstream analyses including survival analysis, gene set enrichment analysis (GSEA), inference on immune cell infiltration and analysis of mutation burden. Receiving operator curve analysis was also performed. A total of 7071 DEGs were first identified by edgeR package, pink module was found significantly associated with invasive lobular carcinoma (ILC). 105 prognostic genes and 9 predictors were identified, allowing the identification of a 5-key prognostic genes (LRRC77P, CA3, BAMBI, CABP1, ATP8A2) after intersection. These 5 genes, and the resulting Cox model, displayed good prognostic performance. Furthermore, distinct differences existed between two risk-score stratified groups at various levels. The identified 5-gene prognostic model will help deepen the understanding of the molecular and immunological mechanisms that affect the survival of LumA-ILC patients and guide and proper monitoring of these patients.

摘要

乳腺癌是一种破坏性的恶性肿瘤,其中 luminal A (LumA) 乳腺癌是最常见的亚型。在本研究中,我们使用了综合的生物信息学方法,希望为 LumA 乳腺癌患者找到新的预后生物标志物。从 TCGA 数据库下载了 611 例 LumA 乳腺癌患者的转录组谱。首先通过差异表达分析鉴定肿瘤样本和对照之间的差异表达基因 (DEGs),然后用于加权基因共表达网络分析。随后的单变量 Cox 回归和 LASSO 算法用于揭示关键的预后基因,以构建多变量 Cox 回归模型。根据风险评分将患者分为高危和低危组,并进行了多种下游分析,包括生存分析、基因集富集分析 (GSEA)、免疫细胞浸润推断和突变负担分析。还进行了接收者操作特征曲线分析。首先通过 edgeR 包鉴定了 7071 个 DEGs,发现粉色模块与浸润性小叶癌 (ILC) 显著相关。鉴定出 105 个预后基因和 9 个预测因子,经交集后确定了 5 个关键预后基因 (LRRC77P、CA3、BAMBI、CABP1、ATP8A2)。这 5 个基因和由此产生的 Cox 模型显示出良好的预后性能。此外,两个风险评分分层组在各个层面存在明显差异。所确定的 5 基因预后模型将有助于加深对影响 LumA-ILC 患者生存的分子和免疫学机制的理解,并指导和适当监测这些患者。

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