EHD2 inhibits the invasive ability of lung adenocarcinoma and improves the prognosis of patients

Sheng Wei; Jingjing Shao; Jinming Wang; Tianye Zhao; Jia Liu; Xiying Shen; Yidan Wang; Haizhen Chen; Gaoren Wang

doi:10.21037/jtd-22-842

EHD2 inhibits the invasive ability of lung adenocarcinoma and improves the prognosis of patients

J Thorac Dis. 2022 Jul;14(7):2652-2664. doi: 10.21037/jtd-22-842.

Authors

Sheng Wei^#¹, Jingjing Shao^#², Jinming Wang³, Tianye Zhao², Jia Liu², Xiying Shen², Yidan Wang², Haizhen Chen², Gaoren Wang¹

Affiliations

¹ Department of Radiotherapy, Affiliated Tumor Hospital of Nantong University, Nantong University, Nantong, China.
² Key Laboratory of Cancer Research Center Nantong, Affiliated Tumor Hospital of Nantong University, Nantong University, Nantong, China.
³ Department of Oncology, Affiliated Tumor Hospital of Nantong University, Nantong University, Nantong, China.

^# Contributed equally.

Abstract

Background: EH domain contains protein 2 (EHD2) may be involved in tumorigenesis and development. However, the role of EHD2 in lung adenocarcinoma (LUAD) is unknown.

Methods: The link between EHD2 and LUAD and the associated underlying mechanism was determined using bioinformatics analysis. Then, immunohistochemistry (IHC) was employed to detect EHD2 expression level in LUAD patients. The stable transfection cell line was used to establish with lentivirus vector, and then the transfection efficiency was detected by western blot. Phagokinetic motility assays, transwell assays, and western blotting were also employed to investigate EHD2 impacts on cell viability.

Results: The results indicated that EHD2 protein expression in human LUAD samples was significantly lower than that in the adjacent normal tissues. Low EHD2 expression was significantly linked to lymph node metastasis as well as advanced tumor-node-metastasis (TNM) staging (P<0.05). The Kaplan-Meier survival curve showed that low EHD2 expression was significantly associated with low survival (P=0.01). The multivariate Cox regression analysis confirmed that EHD2 expression and TNM stage were independent prognostic factors for LUAD patients (all P<0.05). The in vitro experiments demonstrated that EHD2 knockdown markedly contributed to an increase in migration and invasion in A549 cells. Overexpression of EHD2 substantially suppressed H1299 cell migration and invasion. Furthermore, decreased E-cadherin expression was observed in A549 cells with EHD2 knockdown, as well as increased N-cadherin and vimentin expressions. By contrast, E-cadherin expression was increased in H1299 cells, whereas N-cadherin and vimentin expressions were decreased as a result of EHD2 overexpression.

Conclusions: Our study demonstrated that EHD2 reduces LUAD migration and invasion by preventing the epithelial-mesenchymal transition (EMT) process. Furthermore, the results suggest that EHD2 may be a novel biomarker for prognosis prediction.

Keywords: EHD2; Lung adenocarcinoma; epithelial-mesenchymal transition (EMT); overall survival (OS).