Combined Metabolomics with Transcriptomics Reveals Important Serum Biomarkers Correlated with Lung Cancer Proliferation through a Calcium Signaling Pathway

代谢组学 肺癌 转录组 通路分析 生物标志物 生物 油酸 诊断生物标志物 蛋白质组学 癌症 生物标志物发现 计算生物学 癌症研究 生物化学 医学 生物信息学 肿瘤科 内科学 基因表达 基因
作者
Zheng Yuan,Zhuoru He,Yu Kong,Xinjie Huang,Wei Zhu,Zhongqiu Liu,Lingzhi Gong
出处
期刊:Journal of Proteome Research [American Chemical Society]
卷期号:20 (7): 3444-3454 被引量:17
标识
DOI:10.1021/acs.jproteome.0c01019
摘要

Lung cancer (LC) is one of the most malignant cancers in the world, but currently, it lacks effective noninvasive biomarkers to assist its early diagnosis. Our study aims to discover potential serum diagnostic biomarkers for LC. In our study, untargeted serum metabolomics of a discovery cohort and targeted analysis of a test cohort were performed based on gas chromatography–mass spectrometry. Both univariate and multivariate statistical analyses were employed to screen for differential metabolites between LC and healthy control (HC), followed by the selection of candidate biomarkers through multiple algorithms. The results showed that 15 metabolites were significantly dysregulated between LC and HC, and a panel, comprising cholesterol, oleic acid, myo-inositol, 2-hydroxybutyric acid, and 4-hydroxybutyric acid, was demonstrated to have excellent differentiating capability for LC based on multiple classification modelings. In addition, the molecular interaction analysis combined with transcriptomics revealed a close correlation between the candidate biomarkers and LC proliferation via a Ca2+ signaling pathway. Our study discovered that cholesterol, oleic acid, myo-inositol, 2-hydroxybutyric acid, and 4-hydroxybutyric acid in combination could be a promising diagnostic biomarker for LC, and most importantly, our results will shed some light on the pathophysiological mechanism underlying LC to understand it deeply. The data that support the findings of this study are openly available in MetaboLights at https://www.ebi.ac.uk/metabolights/, reference number MTBLS1517.
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