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Open Access 01-12-2021 | Biomarkers | Research

Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation

Authors: Qunhao Zheng, Zhiping Wang, Mengyan Zhang, Yilin Yu, Rui Chen, Tianzhu Lu, Lingyun Liu, Jiayu Ma, Tianxiu Liu, Hongying Zheng, Hui Li, Jiancheng Li

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD.

Methods

Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan–Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC).

Results

SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297–2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = − 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell.

Conclusion

Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

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Title: Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
Authors: Qunhao Zheng
Zhiping Wang
Mengyan Zhang
Yilin Yu
Rui Chen
Tianzhu Lu
Lingyun Liu
Jiayu Ma
Tianxiu Liu
Hongying Zheng
Hui Li
Jiancheng Li
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Biomarkers
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08957-4

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Abstract

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