Wen Shaodi, Zou Renrui, Du Xiaoyue, Pan Rongtian, Li Rutao, Xia Jingwei, Xu Cong, Wang Ruotong, Jiang Feng, Zhou Guoren, Feng Jifeng, Zhu Miaolin, Wang Xin, Shen Bo
Department of Oncology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu, Nanjing 21000, China.
Heliyon. 2024 Mar 7;10(6):e27170. doi: 10.1016/j.heliyon.2024.e27170. eCollection 2024 Mar 30.
Malignant tumours, particularly non-small cell lung cancer (NSCLC), pose a significant threat to human health due to their prevalence and lethality. Treatment methods for NSCLC vary greatly among individuals, making it crucial to identify predictive markers. Moreover, during tumour initiation and progression, tumour cells can release signaling molecules to induce polarization of macrophages towards a more tumour friendly M2 phenotype, which can promote tumour growth, metastasis, and drug resistance.
We employed a comprehensive approach, combining bulk RNA-seq and single-cell sequencing analysis.
In our study, we used bulk RNA-seq and single-cell sequencing methods to analyze differential cells in NSCLC and adjacent tissues, searching for relevant marker genes that can predict prognosis and drug efficacy. We scrutinized biological phenomena such as macrophage-related gene methylation, copy number variation, and alternative splicing. Additionally, we utilized a co-culture technique of immune and tumour cells to explore the role of these genes in macrophage polarization. Our findings revealed distinct differences in macrophages between cancerous and adjacent tissues. We identified ANP32A, CCL20, ERAP2, MYD88, TMEM126B, TUBB6, and ZNF655 as macrophage-related genes that correlate with NSCLC patient prognosis and immunotherapy efficacy. Notably, ERAP2, TUBB6, CCL20, and TMEM126B can induce macrophage M0 to M2 polarization, promoting tumour proliferation.
These findings significantly contribute to our understanding of the NSCLC tumour immune microenvironment. They pave the way for further research into the potential of these genes as targets for regulating tumour occurrence and development.
恶性肿瘤，尤其是非小细胞肺癌（NSCLC），因其高发性和致死性对人类健康构成重大威胁。NSCLC的治疗方法因人而异，因此识别预测标志物至关重要。此外，在肿瘤发生和进展过程中，肿瘤细胞可释放信号分子，诱导巨噬细胞向更有利于肿瘤的M2表型极化，从而促进肿瘤生长、转移和耐药。
我们采用了一种综合方法，将批量RNA测序和单细胞测序分析相结合。
在我们的研究中，我们使用批量RNA测序和单细胞测序方法分析NSCLC及癌旁组织中的差异细胞，寻找可预测预后和药物疗效的相关标志物基因。我们仔细研究了巨噬细胞相关基因甲基化、拷贝数变异和可变剪接等生物学现象。此外，我们利用免疫细胞与肿瘤细胞的共培养技术，探索这些基因在巨噬细胞极化中的作用。我们的研究结果揭示了癌组织和癌旁组织中巨噬细胞的明显差异。我们确定ANP32A、CCL20、ERAP2、MYD88、TMEM126B、TUBB6和ZNF655为与NSCLC患者预后和免疫治疗疗效相关的巨噬细胞相关基因。值得注意的是，ERAP2、TUBB6、CCL20和TMEM126B可诱导巨噬细胞从M0极化到M2，促进肿瘤增殖。
这些发现显著增进了我们对NSCLC肿瘤免疫微环境的理解。它们为进一步研究这些基因作为调节肿瘤发生和发展靶点的潜力铺平了道路。
