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肺癌中FAS基因表达、预后意义及分子相互作用

FAS gene expression, prognostic significance and molecular interactions in lung cancer.

作者信息

Li Kaimin, Tan Shing Cheng, Yang Zhihao, Li Chenwei

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.

UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.

出版信息

Front Oncol. 2024 Oct 2;14:1473515. doi: 10.3389/fonc.2024.1473515. eCollection 2024.

Abstract

INTRODUCTION

FAS has been implicated in the development of various cancers, but its involvement in lung cancer has not been systematically characterized. In this study, we performed data mining in online tumor databases to investigate the expression, methylation, alterations, protein interactions, co-expression and prognostic significance of FAS in lung cancer.

METHOD

The expression, prognostic significance and molecular interactions of FAS in lung cancer was mined and analyzed using GENT2, GEPIA2, UALCAN, cBioPortal, STRING, GeneMANIA, UCSC Xena, Enrichr, and OSluca databases. FAS expression was subsequently investigated at the protein level in samples from 578 lung cancer patients to understand its protein-level expression. validation of FAS gene expression was performed on H1299, H1993, A549 and HBE cell lines.

RESULT

We found that the expression of FAS was significantly downregulated in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) compared to normal lung tissue. In addition, we observed a higher level of FAS promoter methylation in LUSC tissue than in normal tissue. FAS alterations were rare (1.9%) in lung cancer samples, with deep deletions being more common than missense mutations, which occurred mainly in the TNFR-like cysteine-rich domain and the death domain. We also identified a list of proteins interacting with FAS and genes co-expressed with FAS, with LUAD having 11 co-expressed genes and LUSC having 90 co-expressed genes. Our results also showed that FAS expression has limited prognostic significance (HR=1.302, 95% CI=0.935-1.139, P=0.530). Protein level investigation revealed that FAS expression varied among individuals, with nTPM values ranging from 5.2 to 67.2.

CONCLUSION

This study provides valuable insights into the involvements and characteristics of FAS in lung cancer. Further studies are needed to investigate the clinical significance of FAS alterations in lung cancer and to explore the potential of targeting FAS for therapeutic intervention.

摘要

引言

FAS 已被认为与多种癌症的发生发展有关,但其在肺癌中的作用尚未得到系统的描述。在本研究中,我们对在线肿瘤数据库进行数据挖掘,以研究 FAS 在肺癌中的表达、甲基化、改变、蛋白质相互作用、共表达及预后意义。

方法

使用 GENT2、GEPIA2、UALCAN、cBioPortal、STRING、GeneMANIA、UCSC Xena、Enrichr 和 OSluca 数据库挖掘并分析 FAS 在肺癌中的表达、预后意义及分子相互作用。随后在 578 例肺癌患者的样本中对 FAS 表达进行蛋白质水平研究,以了解其蛋白质水平表达情况。在 H1299、H1993、A549 和 HBE 细胞系上对 FAS 基因表达进行验证。

结果

我们发现,与正常肺组织相比,FAS 在肺腺癌(LUAD)和肺鳞状细胞癌(LUSC)中的表达均显著下调。此外,我们观察到 LUSC 组织中 FAS 启动子甲基化水平高于正常组织。FAS 改变在肺癌样本中很少见(1.9%),深度缺失比错义突变更常见,错义突变主要发生在 TNFR 样富含半胱氨酸结构域和死亡结构域。我们还确定了一系列与 FAS 相互作用的蛋白质和与 FAS 共表达的基因,其中 LUAD 有 11 个共表达基因,LUSC 有 90 个共表达基因。我们的结果还表明,FAS 表达的预后意义有限(HR=1.302,95%CI=0.935-1.139,P=0.530)。蛋白质水平研究表明,FAS 表达在个体间存在差异,nTPM 值范围为 5.2 至 67.2。

结论

本研究为 FAS 在肺癌中的作用及特征提供了有价值的见解。需要进一步研究以探讨 FAS 改变在肺癌中的临床意义,并探索靶向 FAS 进行治疗干预的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe5e/11479862/25d986b6bd77/fonc-14-1473515-g001.jpg

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