研究动态
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CRC 中肿瘤相关巨噬细胞和 M2 巨噬细胞的综合分析:揭示分子异质性并开发新的风险特征。

Integrated analysis of tumor-associated macrophages and M2 macrophages in CRC: unraveling molecular heterogeneity and developing a novel risk signature.

发表日期:2024 May 27
作者: Lujing Shi, Hongtun Mao, Jie Ma
来源: MOLECULAR & CELLULAR PROTEOMICS

摘要:

新兴研究越来越强调肿瘤相关巨噬细胞 (TAM) 和 M2 巨噬细胞在癌症发生、进展和转移中的关键作用,使它们成为各种癌症类型的潜在靶点。本研究的主要目的是发现结直肠癌(CRC)中与 TAM-M2 巨噬细胞相关的新生物标志物,并通过结合单细胞 RNA 测序和批量 RNA-seq 数据来剖析 CRC 的分子异质性。 -表达网络分析(WGCNA),我们通过将从 scRNA-seq 数据获得的 TAM 标记基因与从批量 RNA-seq 数据获得的 M2 巨噬细胞的模块基因相交叉,获得了 TAM-M2 相关基因。我们采用最小绝对收缩和选择算子 (LASSO) Cox 分析从这些 TAM-M2 相关基因中选择预测生物标志物。采用定量聚合酶链反应 (qPCR) 来验证筛选中确定的基因的 mRNA 表达水平。这导致了 TAM-M2 相关签名 (TAMM2RS) 的开发。我们还对不同风险组进行了功能和免疫景观分析。scRNA-seq 和bulk RNA-seq 分析相结合,产生了 377 个 TAM-M2 相关基因。 DAPK1、NAGK 和 TRAF1 成为 CRC 的关键预后基因,通过 LASSO Cox 分析进行了鉴定。利用这些基因,我们构建并验证了 TAMM2RS,证明了其在预测 CRC 患者生存方面的有效性。我们的研究对 CRC 中与 TAM-M2 巨噬细胞相关的分子机制进行了彻底的研究,并揭示了潜在的治疗靶点,为治疗提供了新的见解结直肠癌治疗策略。© 2024。作者。
Emerging investigations have increasingly highlighted the critical role of tumor-associated macrophages (TAMs) and M2 macrophages in cancer development, progression, and metastasis, marking them as potential targets in various cancer types. The main objective of this research is to discover new biomarkers associated with TAM-M2 macrophages in colorectal cancer (CRC) and to dissect the molecular heterogeneity of CRC by combining single-cell RNA sequencing and bulk RNA-seq data.By utilizing weighted gene co-expression network analysis (WGCNA), we acquired TAM-M2-associated genes by intersecting TAM marker genes obtained from scRNA-seq data with module genes of M2 macrophages derived from bulk RNA-seq data. We employed least absolute shrinkage and selection operator (LASSO) Cox analysis to select predictive biomarkers from these TAM-M2-related genes. Quantitative polymerase chain reaction (qPCR) was employed to validate the mRNA expression levels of the genes identified in the screening. This led to the development of the TAM-M2-related signature (TAMM2RS). We also conducted functional and immune landscape analyses of different risk groups.The combination of scRNA-seq and bulk RNA-seq analyses yielded 377 TAM-M2-related genes. DAPK1, NAGK, and TRAF1 emerged as key prognostic genes in CRC, which were identified through LASSO Cox analysis. Utilizing these genes, we constructed and validated the TAMM2RS, demonstrating its effectiveness in predicting survival in CRC patients.Our research offers a thorough investigation into the molecular mechanisms associated with TAM-M2 macrophages in CRC and unveils potential therapeutic targets, offering new insights for treatment strategies in colorectal cancer.© 2024. The Author(s).