Untargeted metabolomic study of lung cancer patients after surgery with curative intent: possible metabolites of good prognosis, intervention failure and recurrence

Abstract

Abstract Background Lung cancer (LC) is a leading cause of mortality claiming more than 1.8 million deaths per year worldwide. Surgery is one of the most effective treatments when the disease is in early stages. The study of metabolic alterations after surgical intervention with curative intent could be used to assess the response to treatment or the detection of cancer recurrence. Methods In this study, we have evaluated the changes in the metabolomic profile in serum samples (n = 110) from preoperative (PRE) and postoperative (POST) LC patients collected at two different timepoints (1 month - A; 3–6 months - B) with respect to a group of healthy people. An untargeted metabolomic platform based on reversed phase (RP) and hydrophilic interaction chromatography (HILIC), both mounted into an ultra-high performance liquid chromatography (UHPLC) coupled to mass spectrometry (MS) was applied. Results A total of 33 altered metabolites belonging to carboxylic acids, organooxygen compounds, prenol lipids, fatty acyls, glycerolipids and glycerophospholipids classes were annotated comparing all the different studied groups. We found a group of metabolites altered in PRE (gabaculine, DG(14:0/22:1), stearamide, proline and E,e-carotene-3,3'-dione) whose levels returned to those of a baseline control group 3–6 months after surgery. Furthermore, humulinic acid A and 3-galactosyllactose levels may predict an unsuccessful surgery because they remained altered after the intervention in some patients. In addition, tranexamic acid could be studied more exhaustively to be proposed for monitoring the postoperative recurrence of the LC because its levels seem to be close to controls after one month of the intervention, but may differ significantly after 3–6 months. Conclusions This study provides unique insights into the metabolic profiles of LC patients after surgery at two different time points with a wide metabolic coverage combining complementary analytical methods.