SEC61G 在肺腺癌中的预后价值：基于生物信息学和体外验证的综合研究。

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

机构信息

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, 350014, China.

Jiangxi Cancer Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

BMC Cancer. 2021 Nov 13;21(1):1216. doi: 10.1186/s12885-021-08957-4.

DOI:10.1186/s12885-021-08957-4

PMID:34774014

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8590767/

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.

摘要

背景

研究表明 Sec61 伽马亚基（SEC61G）在多种肿瘤中过表达，可能作为一种潜在的预后标志物。然而，SEC61G 与肺腺癌（LUAD）之间的相关性尚不清楚。在本研究中，我们旨在证明 SEC61G 基因在 LUAD 中的预后价值和潜在生物学功能。

方法

使用公共数据集进行 SEC61G 表达分析。通过 Kaplan-Meier 生存和 Cox 分析研究 SEC61G 在 LUAD 中的预后价值。通过 cBioPortal 评估 SEC61G 甲基化水平与其 mRNA 表达之间的相关性。此外，使用 MethSurv 确定 LUAD 中 SEC61G 甲基化水平的预后价值。进行功能富集分析以探索 SEC61G 的潜在机制。还应用单样本基因集富集分析（ssGSEA）和 TIMER 在线工具来确定 SEC61G 与免疫过滤之间的相关性。此外，进行细胞功能实验以验证 SEC61G 在肺腺癌细胞（LAC）中的生物学行为。

结果

SEC61G 在多种癌症中上调，包括 LUAD。高 SEC61G 表达与 LUAD 患者的预后不良显著相关。多变量分析表明，在 TCGA 队列中，高 SEC61G 表达是独立的预后因素。（HR=1.760，95%CI：1.297-2.388，p<0.001）。SEC61G 的甲基化水平与 SEC61G 表达呈负相关（R=-0.290，p<0.001），并且 SEC61G 低甲基化的患者总体生存率较差。（p=0.0014）。GO 和 KEGG 分析中显著富集了与细胞增殖相关的术语，如细胞周期和细胞分裂。体外实验表明，SEC61G 的敲低导致 LAC 中的细胞增殖、侵袭减少和促进凋亡。GSEA 分析发现，SEC61G 表达与 E2F 靶标相关。此外，SEC61G 表达与包括 CD4+T 细胞、CD8+T 细胞、B 细胞、巨噬细胞、中性粒细胞和树突状细胞在内的免疫细胞浸润呈负相关。