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皮质醇、可的松和4-甲氧基苯乙酸作为早期检测非小细胞肺癌的潜在血浆生物标志物。

Cortisol, cortisone, and 4-methoxyphenylacetic acid as potential plasma biomarkers for early detection of non-small cell lung cancer.

作者信息

Xiang Chengcheng, Jin Shidai, Zhang Juan, Chen Minjian, Xia Yankai, Shu Yongqian, Guo Renhua

机构信息

1 Department of Medical Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.

2 State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, P.R. China.

出版信息

Int J Biol Markers. 2018 Aug;33(3):314-320. doi: 10.1177/1724600818778754. Epub 2018 Jun 13.

Abstract

BACKGROUND

Lung cancer is the most common cause of cancer-related deaths in men and women worldwide. Novel diagnostic biomarkers are urgently required to enable the early detection and treatment of lung cancer, and using novel methods to explore tumor-related biomarkers is a hot topic in lung cancer research. The purpose of this study was to use ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) metabolomics analysis technology combined with multivariate data processing methods to identify potential plasma biomarkers for non-small cell lung cancer (NSCLC).

METHODS

Plasma samples from 99 NSCLC patients and 112 healthy controls were randomly divided into the screening group and the validation group, respectively. UPLC-MS metabolomics analysis technology combined with multivariate data processing methods were used to identify potential plasma biomarkers for NSCLC.

RESULTS

A total of 254 metabolites were detected and validated in plasma. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) modeling indicated that 28 endogenous metabolites were present at significantly different levels in patients with NSCLC than healthy controls (variable importance in projection (VIP)>1 and P<0.001 (independent samples t-test) in both the screening group and the validation group). Further analysis revealed that cortisol, cortisone, and 4-methoxyphenylacetic acid had high sensitivity and specificity values as biomarkers for discriminating between NSCLC and healthy controls. Significant associations between specific plasma metabolites and the pathological type or stage of NSCLC were also observed.

CONCLUSIONS

Metabolomics has the potential to distinguish between NSCLC patients and healthy controls, and may reveal new plasma biomarkers for the early detection of NSCLC.

摘要

背景

肺癌是全球男性和女性癌症相关死亡的最常见原因。迫切需要新的诊断生物标志物以实现肺癌的早期检测和治疗,并且使用新方法探索肿瘤相关生物标志物是肺癌研究中的一个热门话题。本研究的目的是使用超高效液相色谱-串联质谱(UPLC-MS)代谢组学分析技术结合多变量数据处理方法来鉴定非小细胞肺癌(NSCLC)潜在的血浆生物标志物。

方法

将99例NSCLC患者和112例健康对照的血浆样本分别随机分为筛查组和验证组。使用UPLC-MS代谢组学分析技术结合多变量数据处理方法来鉴定NSCLC潜在的血浆生物标志物。

结果

共检测并验证了血浆中的254种代谢物。正交投影到潜在结构判别分析(OPLS-DA)模型表明,与健康对照相比,NSCLC患者体内有28种内源性代谢物的水平存在显著差异(在筛查组和验证组中投影变量重要性(VIP)>1且P<0.001(独立样本t检验))。进一步分析显示,皮质醇、可的松和4-甲氧基苯乙酸作为区分NSCLC和健康对照的生物标志物具有较高的敏感性和特异性值。还观察到特定血浆代谢物与NSCLC的病理类型或分期之间存在显著关联。

结论

代谢组学有潜力区分NSCLC患者和健康对照,并可能揭示用于NSCLC早期检测的新的血浆生物标志物。

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