GPR115 Contributes to Lung Adenocarcinoma Metastasis Associated With LAMC2 and Predicts a Poor Prognosis.

Yingjing Wang,Xiaoyu Zhou,Nan Yang,Liqin Xu,Muqi Shi

doi:10.3389/fonc.2020.577530

Abstract

GPR115, a member of the adhesion G protein-coupled receptor family, is dysregulated in many cancers. However, the expression and function of GRP115 in non-small cell lung cancer (NSCLC) is not clear. Here, we examined the expression pattern, clinical significance, and function of GPR115 in NSCLC by analysis of clinical specimens and human cell lines and bioinformatics analysis. Immunohistochemical analysis of clinical samples showed that GPR115 was significantly upregulated in NSCLC tissues compares with normal lung epithelial tissue (P < 0.05). And GPR115 overexpression is an independent prognostic factor for 5-year overall survival of NSCLC patients [hazard ratio (HR)=1.625, P = 0.008]. Interestingly, higher expression of GPR115 was strongly correlation with differentiation level (P = 0.027), tumor size (P = 0.010), lymph node metastasis (P = 0.022), tumor-node-metastasis stage (P = 0.008), and poor prognosis of lung adenocarcinoma (LUAD, all P = 0.039), but not lung squamous cell carcinoma (LUSC, P > 0.05). Moreover, downregulation of GPR115 by RNA interference in human lung cancer lines inhibited cell proliferation, migration, and invasion. Preliminary bioinformatic analysis confirmed that GPR115 was closely associated with LAMC2 (Spearman correlation coefficient=0.67, P < 0.05), which was accumulated in ECM-receptor interaction and focal adhesion. Consistent with these findings, deceased of GPR115 was associated with E-cadherin, N-cadherin and Vimentin confirmed by western blot. In conclusion, these data suggest that GPR115 may play a role in the tumor growth and metastasis and may have utility as a diagnostic and prognostic marker for LUAD, but not LUSC.

Highlights

Lung cancer is responsible for 18.4% of all deaths from cancer and is the leading cause of cancer-related death worldwide
GPR115 expression level, gender, differentiation, TNM stage, tumor size, and lymph node metastasis were significantly correlated with 5-year survival of Nonsmall cell lung cancer (NSCLC) patients in univariate analysis
We first confirmed that GPR115 was significantly overexpression in NSCLC tissues than normal lung epithelial tissue, which consistent with the higher expression found in breast cancer and colon cancer [14]

Summary

Introduction

Lung cancer is responsible for 18.4% of all deaths from cancer and is the leading cause of cancer-related death worldwide. Nonsmall cell lung cancer (NSCLC) accounts for 80–85% of total lung cancer cases [1, 2]. The most common histological subtypes of NSCLC are lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) which account for approximately 50% and 30% of NSCLC cases, respectively [3]. Many tumor-associated genes are known to be aberrantly expressed in NSCLC [4,5,6] but its pathogenesis is still unclear. Even with the advent of targeted therapy and immunotherapy, the 5-year survival rate from NSCLC is only 16% [7]. Further understanding of the molecular mechanisms underlying the development and progression of NSCLC is needed to provide new directions for developing more effective diagnostic and therapeutic approaches

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Results

Conclusion