Metabolic profiles of serum samples from ground glass opacity represent potential diagnostic biomarkers for lung cancer.

Background: Lung cancer is a leading cause of cancer deaths worldwide. Low-dose computed tomography (LDCT) screening trials indicated that LDCT is effective for the early detection of lung cancer, but the findings were accompanied by high false positive rates. Therefore, the detection of lung cancer needs complementary blood biomarker tests to reduce false positive rates. Methods: In order to evaluate the potential of metabolite biomarkers for diagnosing lung cancer and increasing the effectiveness of clinical interventions, serum samples from subjects participating in a low-dose CT-scan screening were analyzed by using untargeted liquid chromatography-hybrid quadrupole time-offlight mass spectrometry (LC-Q-TOF-MS). Samples were acquired from 34 lung patients with ground glass opacity diagnosed lung cancer and 39 healthy controls. Results: In total, we identified 9 metabolites in electron spray ionization (ESI)(+) mode and 7 metabolites in ESI(-) mode. L-(+)-gulose, phosphatidylethanolamine (PE)(22: 2(13Z, 16Z)/15:0), cysteinyl-glutamine, S-japonin, threoninyl-glutamine, chlorate, 3-oxoadipic acid, dukunolide A, and malonic semialdehyde levels were observed to be elevated in serum samples of lung cancer cases when compared to those of healthy controls. By contrast, 1-(2-furanylmethyl)-1H-pyrrole, 2,4-dihydroxybenzoic acid, monoethyl carbonate, guanidinosuccinic acid, pseudouridine, DIMBOA-Glc, and 4-feruloyl-1,5-quinolactone levels were lower in serum samples of lung cancer cases compared with those of healthy controls. Conclusions: This study demonstrates evidence of early metabolic alterations that can possibly distinguish malignant ground glass opacity from benign ground glass opacity. Further studies in larger pools of samples are warranted.