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考虑治疗和非治疗研究的肺癌生物标志物基因的计算识别。

Computational identification of biomarker genes for lung cancer considering treatment and non-treatment studies.

机构信息

School of Computing and Information Sciences, Florida International University, Miami, FL, USA.

School of Natural Sciences and Mathematics, Claflin University, Orangeburg, SC, USA.

出版信息

BMC Bioinformatics. 2020 Dec 3;21(Suppl 9):218. doi: 10.1186/s12859-020-3524-8.

Abstract

BACKGROUND

Lung cancer is the number one cancer killer in the world with more than 142,670 deaths estimated in the United States alone in the year 2019. Consequently, there is an overreaching need to identify the key biomarkers for lung cancer. The aim of this study is to computationally identify biomarker genes for lung cancer that can aid in its diagnosis and treatment. The gene expression profiles of two different types of studies, namely non-treatment and treatment, are considered for discovering biomarker genes. In non-treatment studies healthy samples are control and cancer samples are cases. Whereas, in treatment studies, controls are cancer cell lines without treatment and cases are cancer cell lines with treatment.

RESULTS

The Differentially Expressed Genes (DEGs) for lung cancer were isolated from Gene Expression Omnibus (GEO) database using R software tool GEO2R. A total of 407 DEGs (254 upregulated and 153 downregulated) from non-treatment studies and 547 DEGs (133 upregulated and 414 downregulated) from treatment studies were isolated. Two Cytoscape apps, namely, CytoHubba and MCODE, were used for identifying biomarker genes from functional networks developed using DEG genes. This study discovered two distinct sets of biomarker genes - one from non-treatment studies and the other from treatment studies, each set containing 16 genes. Survival analysis results show that most non-treatment biomarker genes have prognostic capability by indicating low-expression groups have higher chance of survival compare to high-expression groups. Whereas, most treatment biomarkers have prognostic capability by indicating high-expression groups have higher chance of survival compare to low-expression groups.

CONCLUSION

A computational framework is developed to identify biomarker genes for lung cancer using gene expression profiles. Two different types of studies - non-treatment and treatment - are considered for experiment. Most of the biomarker genes from non-treatment studies are part of mitosis and play vital role in DNA repair and cell-cycle regulation. Whereas, most of the biomarker genes from treatment studies are associated to ubiquitination and cellular response to stress. This study discovered a list of biomarkers, which would help experimental scientists to design a lab experiment for further exploration of detail dynamics of lung cancer development.

摘要

背景

肺癌是全球头号癌症杀手,仅在美国,2019 年就有超过 142670 人死亡。因此,迫切需要确定肺癌的关键生物标志物。本研究的目的是通过计算方法确定肺癌的生物标志物基因,以辅助其诊断和治疗。考虑了两种不同类型的研究,即非治疗和治疗的基因表达谱,以发现生物标志物基因。在非治疗研究中,健康样本为对照,癌症样本为病例。而在治疗研究中,对照为未经治疗的癌细胞系,病例为经治疗的癌细胞系。

结果

使用 R 软件工具 GEO2R 从基因表达综合数据库(GEO)中分离出肺癌的差异表达基因(DEG)。从非治疗研究中分离出 407 个 DEG(254 个上调和 153 个下调),从治疗研究中分离出 547 个 DEG(133 个上调和 414 个下调)。使用两个 Cytoscape 应用程序,即 CytoHubba 和 MCODE,从使用 DEG 基因开发的功能网络中识别生物标志物基因。本研究从非治疗研究和治疗研究中分别发现了两组不同的生物标志物基因,每组包含 16 个基因。生存分析结果表明,大多数非治疗生物标志物基因具有预后能力,表明低表达组的生存机会高于高表达组。而大多数治疗生物标志物基因具有预后能力,表明高表达组的生存机会高于低表达组。

结论

开发了一种使用基因表达谱识别肺癌生物标志物的计算框架。考虑了两种不同类型的研究,即非治疗和治疗。非治疗研究中的大多数生物标志物基因都参与有丝分裂,在 DNA 修复和细胞周期调控中发挥重要作用。而治疗研究中的大多数生物标志物基因都与泛素化和细胞对压力的反应有关。本研究发现了一系列生物标志物,这将有助于实验科学家设计实验室实验,进一步探索肺癌发展的详细动态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6771/7713218/58ebc2d87212/12859_2020_3524_Fig1_HTML.jpg

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