LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

Meiyuan Liu; Rui Cai; Tian Wang; Xia Yang; Meng Wang; Zhongsheng Kuang; Yuhui Xie; Jiren Zhang; Yanfang Zheng

doi:10.21037/atm-21-4507

LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

Ann Transl Med. 2021 Sep;9(17):1392. doi: 10.21037/atm-21-4507.

Authors

Meiyuan Liu^{1

2}, Rui Cai², Tian Wang¹, Xia Yang², Meng Wang², Zhongsheng Kuang³, Yuhui Xie³, Jiren Zhang¹, Yanfang Zheng²

Affiliations

¹ Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
² Department of Medical Oncology, Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou, China.
³ Department of Pathology, The First Affiliated Hospital of Guangzhou Traditional Chinese Medicine University, Guangzhou, China.

Abstract

Background: 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.

Methods: 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 in vitro. 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.

Results: 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 in vitro. 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 LAMC2 was correlated with focal adhesion and extracellular matrix receptor interaction.

Conclusions: 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.

Keywords: LAMC2; immune cell; macrophage; non-small-cell lung cancer (NSCLC); tumor microenvironment (TME).