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基于公开转录组学数据的系统生物学分析揭示 AKR1B10 基因表达、吸烟与肺癌发生之间的关键联系。

Systems biology analysis of publicly available transcriptomic data reveals a critical link between AKR1B10 gene expression, smoking and occurrence of lung cancer.

机构信息

Instituto Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, Bahia, Brazil.

Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

出版信息

PLoS One. 2020 Feb 25;15(2):e0222552. doi: 10.1371/journal.pone.0222552. eCollection 2020.

Abstract

BACKGROUND

Cigarette smoking is associated with an increased risk of developing respiratory diseases and various types of cancer. Early identification of such unfavorable outcomes in patients who smoke is critical for optimizing personalized medical care.

METHODS

Here, we perform a comprehensive analysis using Systems Biology tools of publicly available data from a total of 6 transcriptomic studies, which examined different specimens of lung tissue and/or cells of smokers and nonsmokers to identify potential markers associated with lung cancer.

RESULTS

Expression level of 22 genes was capable of classifying smokers from non-smokers. A machine learning algorithm revealed that AKR1B10 was the most informative gene among the 22 differentially expressed genes (DEGs) accounting for the classification of the clinical groups. AKR1B10 expression was higher in smokers compared to non-smokers in datasets examining small and large airway epithelia, but not in the data from a study of sorted alveolar macrophages. Moreover, AKR1B10 expression was relatively higher in lung cancer specimens compared to matched healthy tissue obtained from nonsmoking individuals. Although the overall accuracy of AKR1B10 expression level in distinction between cancer and healthy lung tissue was 76%, with a specificity of 98%, our results indicated that such marker exhibited low sensitivity, hampering its use for cancer screening such specific setting.

CONCLUSION

The systematic analysis of transcriptomic studies performed here revealed a potential critical link between AKR1B10 expression, smoking and occurrence of lung cancer.

摘要

背景

吸烟与呼吸疾病和各种类型癌症的风险增加有关。早期识别吸烟患者的这些不利结果对于优化个性化医疗至关重要。

方法

在这里,我们使用系统生物学工具对总共 6 项转录组研究的公开数据进行了综合分析,这些研究检查了吸烟者和不吸烟者的不同肺组织标本和/或细胞,以确定与肺癌相关的潜在标志物。

结果

22 个基因的表达水平能够将吸烟者和不吸烟者区分开来。机器学习算法显示,AKR1B10 是 22 个差异表达基因(DEGs)中最具信息量的基因,可用于对临床组进行分类。在检查小气道和大气道上皮的数据集以及从肺泡巨噬细胞的研究数据中,AKR1B10 的表达在吸烟者中高于不吸烟者。此外,AKR1B10 的表达在肺癌标本中相对高于从不吸烟者获得的匹配健康组织。虽然 AKR1B10 表达水平在区分癌症和健康肺组织方面的总体准确性为 76%,特异性为 98%,但我们的结果表明,这种标志物的敏感性较低,阻碍了其在特定环境下用于癌症筛查。

结论

这里进行的转录组研究的系统分析揭示了 AKR1B10 表达、吸烟和肺癌发生之间的潜在关键联系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7ec/7041805/7903bfe764cc/pone.0222552.g001.jpg

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