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Tandem mass spectrometry-based newborn screening strategy could be used to facilitate rapid and sensitive lung cancer diagnosis

Authors huang T, Cao Y, zeng J, Dong J, Sun X, chen J, Gao P

Received 25 October 2015

Accepted for publication 5 January 2016

Published 26 April 2016 Volume 2016:9 Pages 2479—2487

DOI https://doi.org/10.2147/OTT.S99099

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 4

Editor who approved publication: Professor Jianmin Xu


Ting Huang,1,* Yunfeng Cao,1,* Jia Zeng,1 Jun Dong,2 Xiaoyu Sun,2 Jianxing Chen,1 Peng Gao2,3

1Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineer and Technology Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, Shanghai, 2Clinical Laboratory, Dalian Sixth People’s Hospital, 3CASKey Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, People’s Republic of China

*These authors contributed equally to this work

Objective: Newborn screening (NBS) helps in the early detection of inborn errors of metabolism (IEM). The most effective NBS strategy prevailing in clinics is tandem mass spectrometry (MS/MS) analysis using dried blood spot (DBS) samples. Taking lung cancer (LC) as an example, this study tried to explore if this technique could be of any assistance for the discovery of tumor metabolite markers.
Materials and methods: Twenty-six acylcarnitines and 23 amino acids, which are commonly used in IEM screening, were quantified using DBS samples from 222 LC patients, 118 benign lung disease (LD) patients, and 96 healthy volunteers (CONT). Forty-four calculated ratios based on the abovementioned metabolites were also included using MS/MS quantification results.
Results: This pilot study led to the findings of 65 significantly changed amino acids, acylcarnitines, and some of their ratios for the LC, LD, and CONT groups. Among the differential parameters, 12 items showed reverse changing trends between the LC and LD groups compared to the CONT group. Regression analysis demonstrated that six of them – Arg, Pro, C10:1, Arg/Orn, Cit/Arg, and C5-OH/C0 – could be used to diagnose LC with a sensitivity of 91.3% and a specificity of 92.7%.
Conclusion: This study demonstrated the DBS-based MS/MS strategy was a promising tool for the discovery of tumor metabolite markers. Remarkably, this MS/MS analysis could be finished in several minutes, implying that it was a proper measure complementary to the traditional serum protein biomarker quantitation strategy for cancerous disease diagnosis and screening purposes.

Keywords: lung cancer, mass spectrometry, newborn screening tests

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