Non-Invasive Exploration of Metabolic Profile of Lung Cancer with Nuclear Magnetic Resonance Spectroscopy

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Outcomes in lung cancer are generally poor with most patients presenting with advanced stage disease. Early detection improves prognosis when disease can be surgically resected. Currently, there are no biomarkers that have been effective in monitoring treatment response and detecting recurrence early. With the advent of personalized medicine, there is a need for developing novel biomarkers and non-invasive tools such as metabolic profiling of lung cancer. In this study we looked at the metabolic profile in bio fluids of early stage non-small cell lung cancer (NSCLC) patients before and after surgical resection to identify a cancer specific metabolome. This is a prospective study with 57 patients with early stage NSCLC enrolled. Bio-fluids: sputum, exhaled breath condensate (EBC), serum and urine were collected before and after surgery. Clinical data was recorded including TNM staging, SUV, COPD, diabetes, gender, smoking history & PDL1. 38 sample sets (both pre- and post-surgery) were analyzed with nuclear magnetic resonance (NMR) spectroscopy to identify metabolites. 16 patients had confirmed true sputum pre- and post-surgery by identification of macrophages in the sample. Metabolite levels were compared before and after surgery by paired T-test. Pearson correlation analyses were done to examine the relationship between metabolite changes and clinical variables. Groups were compared with Wilcoxon two-sample and Kruskal-Wallis tests. Glucuronate was significantly raised in serum and sputum samples of lung cancer patients prior to surgery (p<0.05). Serine was raised in sputum pre-surgery samples. Post-operatively, glucose levels in the urine were 3x higher, while lactate increased in the EBC. Glucose and lactate levels in the urine and serum respectively in the pre- and post-surgery samples differed in diabetic and non-diabetic patients (p<0.05). Urine glucose levels correlated with SUV, clinical & pathological tumor size both before and after surgical resection (p<0.05). A correlation between pre-op EBC lactate levels and clinical tumor size was also identified. Imidazole was raised in the post-operative urine samples and was significantly different in the pre-surgery urine samples for patients with(out) COPD and smoking status. In the confirmed sputum samples, we identified that propylene glycol was significantly decreased after surgery (p = 0.019). There was also a statistically significant difference in serum pre-surgery propylene glycol levels for different PDL1 expression levels (p = 0.041). Finally, propylene glycol levels in the preoperative serum samples correlated with clinical tumor size (p = 0.012). We identified several changes in the metabolic profile of body fluids of patients with early stage NSCLC obtained before and after curative surgical resection using NMR spectroscopy. Further work is needed to characterize a cancer specific metabolic phenotype of lung cancer for in vitro diagnostics.