Simultaneous quantification of serum monounsaturated and polyunsaturated phosphatidylcholines as potential biomarkers for diagnosing non-small cell lung cancer

Yingrong Chen,Jianbin Zhang,Licheng Dai,Hongwei Li,Wei Wu,Zhihong Ma,Limin Xu,Lishan Min,Jing Zhong,Liqin Li

doi:10.1038/s41598-018-25552-z

Yingrong Chen, Jianbin Zhang + Show 8 more

Open Access

https://doi.org/10.1038/s41598-018-25552-z

Copy DOI

Journal: Scientific Reports	Publication Date: May 8, 2018
Citations: 50	License type: open-access

Affiliation: Huzhou Central Hospital

Abstract

Non-small cell lung cancer (NSCLC) is one of the most common malignancies worldwide. In this study, we investigated Ultrahigh Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry and Gas Chromatography Time-of-Flight/Mass Spectrometry-based non-targeted metabolomic profiles of serum samples obtained from early-stage NSCLC patients and healthy controls (HC). Metabolic pathways and the biological relevance of potential biomarkers were extensively studied to gain insights into dysregulated metabolism in NSCLC. The identified biomarker candidates were further externally validated via a targeted metabolomics analysis. The global metabolomics profiles could clearly distinguish NSCLC patients from HC. Phosphatidylcholine (PC) levels were found to be dysregulated in glycerophospholipid (GPL) metabolism, which was the top altered pathway in early-stage NSCLC. Compared with those in HC, significant increases in the levels of saturated and monounsaturated PCs such as PC (15:0/18:1), PC (18:0/16:0) and PC (18:0/20:1) were observed in NSCLC. Additionally, relative to those in HC, the levels of 9 polyunsaturated PCs, namely, PC (17:2/2:0), PC (18:4/3:0), and PC (15:0/18:2), and so on were significantly decreased in NSCLC patients. A panel of 12 altered PCs had good diagnostic performance in differentiating early-stage NSCLC patients from HC, and these PCs may thus be used as serum biomarkers for the early diagnosis of NSCLC.

Highlights

Lung cancer is one of the most common malignancies worldwide, with the highest rate of morbidity and mortality
There are a handful of validated small molecular biomarkers for Non-small cell lung cancer (NSCLC) that can be used to avoid the necessity of tumour biopsies for classifying NSCLC
Non-targeted metabolomics was widely applied for identifying NSCLC biomarkers by nuclear magnetic resonance (NMR), HPLC/MS and gas chromatography/mass spectrometry (GC/MS)

Summary

Introduction

Lung cancer is one of the most common malignancies worldwide, with the highest rate of morbidity and mortality. Non-targeted metabolomics approaches involve global profiling of the metabolome to identify different metabolites that can be used for the initial screening of diagnostic biomarkers. Targeted metabolomics approaches use standards to quantify metabolites to validate biomarkers and investigate specific metabolic pathways identified using non-targeted metabolic profiling[17]. To broaden our understanding of metabolic alterations in NSCLC and to identify potential biomarkers for early diagnosis, 90 early-stage NSCLC patients and 90 healthy controls (HC) were enrolled in a study involving Ultrahigh Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-Q-TOF/MS) and Gas Chromatography Time-of-Flight/Mass Spectrometry (GC-TOF/MS)-based non-targeted metabolomics analysis. Metabolic pathways and biological relevance of potential biomarkers were extensively studied to gain insights into dysregulated metabolism in early-stage NSCLC. The identified biomarker candidates were further externally validated in a cohort including 30 early-stage NSCLC patients and 30 HC by a targeted metabolomics analysis

Methods

Results

Conclusion