Study of early stage non-small-cell lung cancer using Orbitrap-based global serum metabolomics

Abstract

PurposeThe aim of the project was to apply ultra-high-performance liquid chromatography–quadrupole-Orbitrap-high-resolution mass spectrometry for serum metabolite profiling of non-small-cell lung cancer (NSCLC). This Orbitrap-based methodology has been applied for a study of NSCLC potential markers for the first time.MethodsAfter extraction using protein precipitation, sera were separated on the ACE Excel 2 C18-PFP (100 × 2.1 mm, 2.0 µm) column using gradient elution and analyzed within the range of 70–1000 m/z. Only patients with early stage disease (stages IA–IIB) were included in the study, providing opportunity to find biomarkers for early lung cancer detection. The resulting metabolite profiles were subjected to univariate and multivariate statistical tests.Results36 features were found significantly changed between NSCLC group and controls after FDR adjustment and 19 were identified using various metabolite databases (in-house library, HMDB, mzCloud). The study revealed a number of NSCLC biomarker candidates which belong to such compound classes as acylcarnitines, organic acids, and amino acids. Multivariate ROC curve built using 12 identified metabolites was characterized by AUC = 0.836 (0.722–0.946). There were no significant differences in the serum metabolite profiles between two most common histological types of lung cancer—adenocarcinoma and squamous cell carcinoma.ConclusionsThrough identification of novel potential tumor markers, Orbitrap-based global metabolic profiling is a useful strategy in cancer research. Our study can accelerate development of new diagnostic and therapeutic strategies in NSCLC. The metabolites involved in discrimination between NSCLC patients and the control subjects should be further explored using a targeted approach.Electronic supplementary materialThe online version of this article (doi:10.1007/s00432-017-2347-0) contains supplementary material, which is available to authorized users.

A High-Performing Plasma Metabolite Panel for Early-Stage Lung Cancer Detection

“…In our study, plasma carnitine levels were significantly increased-across all NSCLC stages. Increased production of carnitine has also been identified as a significant feature of plasma, tumor tissue, and other types of biofluids acquired from NSCLC patients [60] as well as patients with other types of cancer, such as bladder [61], breast [62], and colorectal cancer [63]. Carnitine is rapidly consumed by tumor cells for acetyl-CoA synthesis and acetyl-CoA can be used for lipid synthesis via glutamine metabolism [56,64,65].…”

Multi-class analysis for simultaneous determination of pesticides, mycotoxins, process-induced toxicants and packaging contaminants in tea

“…Therefore the C18-PFP phase, combining the strength of C18-chains (hydrophobicity) and PFP-groups (hydrogen bonds, dipole-dipole and - interactions) and affording possible enhanced retention of polar compounds, has been chosen. To date, while some studies combined C18 and PFP phases using two successive columns in LCxLC applications (Mena-Bravo, Priego-Capote, & Luque de Castro, 2016), only two applications dealing with a C18-PFP column have been published yet, for analyzes in rat plasma (Zgair et al, 2015) and markers of lung cancer in human serum (Klupczynska et al, 2017). Thus, the potential of this new stationary phase for the separation of multi-class contaminants in food samples is described here for the first time.…”

Next-generation metabolomics in lung cancer diagnosis, treatment and precision medicine: mini review

“…Acylcarnitines are also the indicators of mitochondrial normal functions. Serum acylcarnitines were found to be significantly lower in early NSCLC [ 34 ]. (2) Amino acids and protein biosynthesis such as threonine, alanine and glutamic acid.…”