Abstract
BackgroundStudies 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.MethodsPublic 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).ResultsSEC61G 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.ConclusionOur 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.
Highlights
Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker
Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of lung adenocarcinoma (LUAD) patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD
SEC61G is overexpressed in lung adenocarcinoma The results showed that SEC61G was highly expressed in lung adenocarcinoma tissue compared with normal tissue (p < 0.001) (Fig. 1A)
Summary
Studies have shown that the Sec gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. Lung adenocarcinoma (LUAD) is the most frequently diagnosed histological subtype of nonsmall cell lung cancer (NSCLC), followed by squamous cell carcinoma [2]. Various factors such as cigarette smoking, second-hand or passive smoking, air pollution, genetic alteration, asbestos, and radon put individuals under the risk of LUAD [3]. Alternative treatments such as targeted therapy and immune therapy for LUAD patients have been progressed rapidly over the past decades, the average 5-year survival rate of patients with LUAD remains less than 20% [4, 5]. It is of vital importance to keep searching for new tumor biomarkers and other potential genetic targets [6]
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