Liu Meiyuan, Cai Rui, Wang Tian, Yang Xia, Wang Meng, Kuang Zhongsheng, Xie Yuhui, Zhang Jiren, Zheng Yanfang
Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Department of Medical Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
Ann Transl Med. 2021 Sep;9(17):1392. doi: 10.21037/atm-21-4507.
Non-small-cell lung cancer (NSCLC) is the most prevalent cancer worldwide. Tumor microenvironment (TME) plays a very important role in the cancer development. Thus, it is urgent to find the change of TME that contributes to NSCLC carcinogenesis and progression.
The bioinformatics analysis approach was applied to evaluate the change of TME and screen the differentially immune cells in NSCLC tissue based on The Cancer Genome Atlas (TCGA) data. Meanwhile, the association of differentially immune cells with tumor stage and prognosis of NSCLC was evaluated. Then, we screen the different expression genes between macrophages infiltration high group and low group. After that, the expression of LAMC2 was detected in 48 cases of NSCLC tissues and paired normal tissues. The function of LAMC2 was detected through cell experiments . Immunohistochemistry assay was used to detect the correlation between LAMC2 expression and macrophages infiltration in NSCLC tissue. LAMC2-related pathways were identified by gene set enrichment analysis.
Compared with early stage, middle-advanced stage of NSCLC exhibited lower immune score. Macrophages were the main component of different immune cells and correlated with poor outcome. The results of immunohistochemistry indicated that the expression of LAMC2 in NSCLC tissues was higher than paired normal tissues. Down-regulation of LAMC2 inhibited the proliferation, migration and invasion of NSCLC cells . Overexpression of LAMC2 was positively associated with macrophages infiltration in NSCLC tissues. Inhibition of LAMC2 expression in NSCLC cells could reduce THP-1 infiltration, and LAMC2 protein could promote the infiltration of THP-1. The Gene Set Enrichment Analysis results showed that high expression of was correlated with focal adhesion and extracellular matrix receptor interaction.
Immune suppression and macrophages infiltration were correlated with poor outcomes in NSCLC. LAMC2 promoted macrophages infiltration and extracellular matrix remolding in NSCLC. Our studies suggested an oncogenic role of LAMC2 in NSCLC progression and it perhaps serve as a potential immune therapy target for NSCLC.
非小细胞肺癌（NSCLC）是全球最常见的癌症。肿瘤微环境（TME）在癌症发展中起着非常重要的作用。因此，迫切需要找到有助于NSCLC致癌和进展的TME变化。
应用生物信息学分析方法，基于癌症基因组图谱（TCGA）数据评估TME的变化并筛选NSCLC组织中差异免疫细胞。同时，评估差异免疫细胞与NSCLC肿瘤分期和预后的关联。然后，我们筛选巨噬细胞浸润高组和低组之间的差异表达基因。之后，检测48例NSCLC组织和配对正常组织中LAMC2的表达。通过细胞实验检测LAMC2的功能。采用免疫组织化学分析检测NSCLC组织中LAMC2表达与巨噬细胞浸润的相关性。通过基因集富集分析确定LAMC2相关途径。
与早期相比，NSCLC的中晚期免疫评分较低。巨噬细胞是不同免疫细胞的主要成分，与不良预后相关。免疫组织化学结果表明，NSCLC组织中LAMC2的表达高于配对的正常组织。LAMC2的下调抑制了NSCLC细胞的增殖、迁移和侵袭。LAMC2的过表达与NSCLC组织中巨噬细胞浸润呈正相关。抑制NSCLC细胞中LAMC2的表达可减少THP-1浸润，而LAMC2蛋白可促进THP-1的浸润。基因集富集分析结果表明，LAMC2的高表达与粘着斑和细胞外基质受体相互作用相关。
免疫抑制和巨噬细胞浸润与NSCLC的不良预后相关。LAMC2促进NSCLC中的巨噬细胞浸润和细胞外基质重塑。我们的研究表明LAMC2在NSCLC进展中具有致癌作用，它可能作为NSCLC的潜在免疫治疗靶点。
