整合大量和单细胞 RNA-seq,构建巨噬细胞相关预后模型,用于三阴性乳腺癌的预后分层

IF 3.3 3区 医学 Q2 ONCOLOGY
Journal of Cancer Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI:10.7150/jca.101042
Hongmeng Zhao, Xuejie Zhou, Guixin Wang, Yue Yu, Yingxi Li, Zhaohui Chen, Wenbin Song, Liwei Zhao, Li Wang, Xin Wang, Xuchen Cao, Yao Tian
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引用次数: 0

摘要

背景:由于治疗手段有限,三阴性乳腺癌(TNBC)是预后较差的乳腺癌亚型。巨噬细胞在肿瘤的生长和存活中起着关键作用。我们的研究旨在探索巨噬细胞在 TNBC 中的异质性,并为 TNBC 预后分层建立一个与巨噬细胞相关的预后模型。材料与方法:采用Seurat软件包分析单细胞RNA表达谱。细胞类型由来自公共研究和在线数据库的标记物确定。细胞-细胞相互作用由 CellChat 软件包计算。Monocle软件包用于可视化巨噬细胞的细胞轨迹。经过一系列筛选,六个与巨噬细胞相关的基因构建了预后模型。六个基因在正常组织和 TNBC 组织中的表达得到了验证。并通过连接图分析了针对高危 TNBC 患者的几种潜在药物。结果共鉴定出九种细胞类型,巨噬细胞在 TNBC 样本中高度富集。值得注意的是,SPP1+肿瘤相关巨噬细胞的预后较差。通过HSPA6、LPL、IDO1、ALDH2、TK1和QPCT构建的预后模型对训练组和外部测试组中TNBC患者的3年、5年总生存期具有良好的预测准确性。最后,通过模型确定了几种针对高危 TNBC 患者的药物。结论我们的研究为阐明TNBC中巨噬细胞的异质性提供了宝贵的资料,也为TNBC的预后风险分层提供了有前途的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Integrating Bulk and Single-cell RNA-seq to Construct a Macrophage-related Prognostic Model for Prognostic Stratification in Triple-negative Breast Cancer.

Background: Triple-negative breast cancer (TNBC) is a poor prognostic subtype of breast cancer due to limited treatment. Macrophage plays a critical role in tumor growth and survival. Our study intends to explore the heterogeneity of macrophage in TNBC and establish a macrophage-related prognostic model for TNBC prognostic stratification. Materials and Methods: Seurat package was conducted to analyze the single-cell RNA expression profilers. The cell types were identified by the markers derived from public research and online database. The cell-cell interactions were calculated by the CellChat package. Monocle package was used to visualize the cell trajectory of macrophages. The prognostic model was constructed by six macrophage-related genes after a series of selections. The expression of six genes were validated in normal and TNBC tissues. And several potential agents for high-risk TNBC patients were analyzed by Connectivity Map analysis. Results: Nine cell types were identified, and the macrophages were highly enriched in TNBC samples. five distinct subgroups of macrophage were identified. Notably, SPP1+ tumor-associated macrophages exhibited a poor prognosis. The prognostic model was constructed by HSPA6, LPL, IDO1, ALDH2, TK1, and QPCT with good predictive accuracy at 3-, 5- years overall survival for TNBC patients in both training and external test cohorts. Finally, several drugs were identified for the high-risk TNBC patients decided by model. Conclusion: Our study provides a valuable source for clarifying macrophage heterogeneity in TNBC, and a promising tool for prognostic risk stratification of TNBC.

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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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