Bioinformatics analysis of the role of lysosome-related genes in breast cancer

This study aimed to investigate the roles of lysosome-related genes in BC prognosis and immunity. Transcriptome data from TCGA and MSigDB, along with lysosome-related gene sets, underwent NMF cluster analysis, resulting in two subtypes. Using lasso regression and univariate/multivariate Cox regression analysis, an 11-gene signature was successfully identified and verified. High- and low-risk populations were dominated by HR+ sample types. There were differences in pathway enrichment, immune cell infiltration, and immune scores. Sensitive drugs targeting model genes were screened using GDSC and CCLE. This study constructed a reliable prognostic model with lysosome-related genes, providing valuable insights for BC clinical immunotherapy. Lysosome-related genes can be used to predict survival outcomes in BRCA patients.Significant differences were showed in the immune status of patient with different prognoses.Immunotherapy may show better therapeutic results in low-risk patients.The most promising targeted drugs in the low-risk group are mainly Lapatinib, Palbociclib and Ribociclib. Lysosome-related genes can be used to predict survival outcomes in BRCA patients. Significant differences were showed in the immune status of patient with different prognoses. Immunotherapy may show better therapeutic results in low-risk patients. The most promising targeted drugs in the low-risk group are mainly Lapatinib, Palbociclib and Ribociclib.

本研究旨在探讨溶酶体相关基因（lysosome-related genes）在乳腺癌（Breast Cancer, BC）预后与免疫状态中的作用。研究获取了癌症基因组图谱（The Cancer Genome Atlas, TCGA）与分子特征数据库（Molecular Signatures Database, MSigDB）的转录组数据，并结合溶酶体相关基因集开展非负矩阵分解（Non-negative Matrix Factorization, NMF）聚类分析，最终得到两个肿瘤亚型。通过LASSO回归及单因素、多因素Cox回归分析，成功构建并验证了一套包含11个基因的预后特征模型。高、低风险人群的样本类型以激素受体阳性（HR+）样本为主。两组在通路富集、免疫细胞浸润及免疫评分方面均存在显著差异。借助癌症药物敏感性基因组学数据库（Genomics of Drug Sensitivity in Cancer, GDSC）与癌症细胞系百科全书（Cancer Cell Line Encyclopedia, CCLE），筛选出了靶向该模型基因的敏感药物。本研究构建的溶酶体相关基因预后模型可靠性良好，可为乳腺癌临床免疫治疗提供极具价值的参考依据。溶酶体相关基因可用于预测乳腺癌（Breast Cancer, BRCA）患者的生存结局；不同预后状态的患者免疫状态存在显著差异；低风险患者或可从免疫治疗中获得更优的治疗效果；低风险组中最具应用前景的靶向药物主要为拉帕替尼（Lapatinib）、帕博西尼（Palbociclib）及瑞博西尼（Ribociclib）。