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

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...

Full description

Bibliographic Details
Main 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
Format: Article
Language:English
Published: BMC 2021-11-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-021-08957-4
_version_ 1819003275745165312
author Qunhao Zheng
Zhiping Wang
Mengyan Zhang
Yilin Yu
Rui Chen
Tianzhu Lu
Lingyun Liu
Jiayu Ma
Tianxiu Liu
Hongying Zheng
Hui Li
Jiancheng Li
author_facet Qunhao Zheng
Zhiping Wang
Mengyan Zhang
Yilin Yu
Rui Chen
Tianzhu Lu
Lingyun Liu
Jiayu Ma
Tianxiu Liu
Hongying Zheng
Hui Li
Jiancheng Li
author_sort Qunhao Zheng
collection DOAJ
description 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.
first_indexed 2024-12-20T23:18:25Z
format Article
id doaj.art-fe7a6cf687e24966832fd6bf854892c5
institution Directory Open Access Journal
issn 1471-2407
language English
last_indexed 2024-12-20T23:18:25Z
publishDate 2021-11-01
publisher BMC
record_format Article
series BMC Cancer
spelling doaj.art-fe7a6cf687e24966832fd6bf854892c52022-12-21T19:23:35ZengBMCBMC Cancer1471-24072021-11-0121111810.1186/s12885-021-08957-4Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validationQunhao Zheng0Zhiping Wang1Mengyan Zhang2Yilin Yu3Rui Chen4Tianzhu Lu5Lingyun Liu6Jiayu Ma7Tianxiu Liu8Hongying Zheng9Hui Li10Jiancheng Li11Fujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalJiangxi Cancer Hospital of Nanchang UniversityJiangxi Cancer Hospital of Nanchang UniversityFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalFujian Medical University Cancer Hospital, Fujian Cancer HospitalAbstract 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.https://doi.org/10.1186/s12885-021-08957-4SEC61GLung adenocarcinomaNovel biomarkersPrognosisProliferationInvasion
spellingShingle Qunhao Zheng
Zhiping Wang
Mengyan Zhang
Yilin Yu
Rui Chen
Tianzhu Lu
Lingyun Liu
Jiayu Ma
Tianxiu Liu
Hongying Zheng
Hui Li
Jiancheng Li
Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
BMC Cancer
SEC61G
Lung adenocarcinoma
Novel biomarkers
Prognosis
Proliferation
Invasion
title Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
title_full Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
title_fullStr Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
title_full_unstemmed Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
title_short Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation
title_sort prognostic value of sec61g in lung adenocarcinoma a comprehensive study based on bioinformatics and in vitro validation
topic SEC61G
Lung adenocarcinoma
Novel biomarkers
Prognosis
Proliferation
Invasion
url https://doi.org/10.1186/s12885-021-08957-4
work_keys_str_mv AT qunhaozheng prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT zhipingwang prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT mengyanzhang prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT yilinyu prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT ruichen prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT tianzhulu prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT lingyunliu prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT jiayuma prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT tianxiuliu prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT hongyingzheng prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT huili prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation
AT jianchengli prognosticvalueofsec61ginlungadenocarcinomaacomprehensivestudybasedonbioinformaticsandinvitrovalidation