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基于集成学习的基因特征与风险模型用于预测三阴性乳腺癌的预后

Ensemble learning-based gene signature and risk model for predicting prognosis of triple-negative breast cancer.

作者信息

Li Tiancheng, Chen Siqi, Zhang Yuqi, Zhao Qianqian, Ma Kai, Jiang Xiwei, Xiang Rongwu, Zhai Fei, Ling Guixia

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.

School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, 110016, China.

出版信息

Funct Integr Genomics. 2023 Mar 14;23(2):81. doi: 10.1007/s10142-023-01009-z.

Abstract

Although medical science has been fully developed, due to the high heterogeneity of triple-negative breast cancer (TNBC), it is still difficult to use reasonable and precise treatment. In this study, based on local optimization-feature screening and genomics screening strategy, we screened 25 feature genes. In multiple machine learning algorithms, feature genes have excellent discriminative diagnostic performance among samples composed of multiple large datasets. After screening at the single-cell level, we identified genes expressed substantially in myeloid cells (MCGs) that have a potential association with TNBC. Based on MCGs, we distinguished two types of TNBC patients who showed considerable differences in survival status and immune-related characteristics. Immune-related gene risk scores (IRGRS) were established, and their validity was verified using validation cohorts. A total of 25 feature genes were obtained, among which CXCL9, CXCL10, CCL7, SPHK1, and TREM1 were identified as the result after single-cell level analysis and screening. According to these entries, the cohort was divided into MCA and MCB subtypes, and the two subtypes had significant differences in survival status and tumor-immune microenvironment. After Lasso-Cox screening, IDO1, GNLY, IRF1, CTLA4, and CXCR6 were selected for constructing IRGRS. There were significant differences in drug sensitivity and immunotherapy sensitivity among high-IRGRS and low-IRGRS groups. We revealed the dynamic relationship between TNBC and TIME, identified a potential biomarker called Granulysin (GNLY) related to immunity, and developed a multi-process machine learning package called "MPMLearning 1.0" in Python.

摘要

尽管医学科学已得到充分发展,但由于三阴性乳腺癌(TNBC)的高度异质性,合理且精确的治疗仍存在困难。在本研究中,基于局部优化特征筛选和基因组筛选策略,我们筛选出了25个特征基因。在多种机器学习算法中,特征基因在由多个大型数据集组成的样本中具有出色的判别诊断性能。在单细胞水平筛选后,我们鉴定出在髓系细胞(MCGs)中大量表达且与TNBC可能相关的基因。基于MCGs,我们区分出了两类TNBC患者,他们在生存状态和免疫相关特征方面存在显著差异。建立了免疫相关基因风险评分(IRGRS),并使用验证队列验证了其有效性。共获得25个特征基因,其中CXCL9、CXCL10、CCL7、SPHK1和TREM1是单细胞水平分析和筛选后的结果。根据这些指标,将队列分为MCA和MCB亚型,这两个亚型在生存状态和肿瘤免疫微环境方面存在显著差异。经过Lasso-Cox筛选,选择IDO1、GNLY、IRF1、CTLA4和CXCR6构建IRGRS。高IRGRS组和低IRGRS组在药物敏感性和免疫治疗敏感性方面存在显著差异。我们揭示了TNBC与肿瘤免疫微环境(TIME)之间的动态关系,鉴定出一种与免疫相关的潜在生物标志物颗粒溶素(GNLY),并在Python中开发了一个名为“MPMLearning 1.0”的多流程机器学习软件包。

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