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.