Prognostic Implication of Metabolic Syndrome in Patients with Nasopharyngeal Carcinoma: A Large Institution-Based Cohort Study from an Endemic Area

Abstract

Objective Metabolic syndrome has been identified as a prognostic predictor in multiple cancers. This study aimed to evaluate the impact of metabolic syndrome on the clinical outcome of patients with nasopharyngeal carcinoma (NPC) and its mechanism. Methods A cohort of 2003 NPC patients with a median follow-up time of 96.3 months (range: 4.1–120.0 months) were enrolled in this analysis. Kaplan–Meier curves and the Log rank test were used to determine the differences in progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS). Univariate and multivariable analyses were used to identify independent prognostic predictors. Untargeted metabolomics (LC-HRMS) was used to detect the serum metabolic profiles of 10 well-matched patients with or without metabolic syndrome. Differential metabolite-based enrichment analysis and pathway analysis were performed to identify the potential mechanism of metabolic syndrome in NPC. Results A total of 171/2003 (8.5%) patients were diagnosed with metabolic syndrome, and these patients tended to be male ( P < 0.001) and older ( P = 0.003). Patients with metabolic syndrome had poorer PFS ( P = 0.011), CSS ( P = 0.003) and OS ( P = 0.001) than those without metabolic syndrome. Univariate and multivariable analyses showed that metabolic syndrome was a statistically significant and independent predictor for PFS (HR: 1.34, 95% CI: 1.03–1.75, P = 0.032), CSS (HR: 1.53, 95% CI: 1.12–2.08, P = 0.008), and OS (HR: 1.50, 95% CI: 1.13–2.00, P = 0.006). The serum metabolic profile of patients with metabolic syndrome was distinct from that of patients without metabolic syndrome. A total of 319 differential metabolites [log2(FC)>1 or log2 (FC)<-1] were identified and were significantly involved in D-glutamine and D-glutamate metabolism, and valine, leucine and isoleucine biosynthesis. Conclusion Metabolic syndrome can serve as a prognostic predictor and guide a more personalized therapy for NPC patients.

Serum and urine metabolomics analyses reveal metabolic pathways and biomarkers in relation to nasopharyngeal carcinoma

“…Among the 181 metabolites significantly changed in the NPC serum, half belongs to lipids and lipid‐like molecules. Some of the 181 metabolites, such as dl ‐glutamic acid, linoleic acid, cholesterol, dl ‐lactate, l ‐pyroglutamic acid, palmitic acid, and arachidonic acid, have been reported to be associated with NPC in previous reports 26–29 . These significantly changed metabolites are enriched in 16 pathways, including biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, and central carbon metabolism in cancer ( p < 0.05).…”

“…Similar to the results in several other studies, pathways such as arginine biosynthesis, biosynthesis of unsaturated fatty acids, D-glutamine and D-glutamate metabolism, fatty acid biosynthesis, and biosynthesis of amino acids were found to be highly associated with NPC development in this study. [26][27][28][29] Cancer-related pathways including aldosterone synthesis and secretion, basal cell carcinoma, cholesterol metabolism, and ferroptosis were also significantly enriched. 30,31 Huang et al reported that cholesterol-derived metabolites and abnormal cholesterol metabolism play important roles in suppressing immune responses and supporting cancer development.…”

“…Some of the 181 metabolites, such as DL-glutamic acid, linoleic acid, cholesterol, DL-lactate, L-pyroglutamic acid, palmitic acid, and arachidonic acid, have been reported to be associated with NPC in previous reports. [26][27][28][29] These significantly changed metabolites are enriched in 16 pathways, including biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, and central carbon metabolism in cancer (p < 0.05). Similar to the results in several other studies, pathways such as arginine biosynthesis, biosynthesis of unsaturated fatty acids, D-glutamine and D-glutamate metabolism, fatty acid biosynthesis, and biosynthesis of amino acids were found to be highly associated with NPC development in this study.…”

“…25 Among these, blood and urine are the most commonly used sample types that could be noninvasively collected in of NPC. [26][27][28][29] Among the 181 metabolites significantly changed in the NPC serum, half belongs to lipids and lipid-like molecules. Some of the 181 metabolites, such as DL-glutamic acid, linoleic acid, cholesterol, DL-lactate, L-pyroglutamic acid, palmitic acid, and arachidonic acid, have been reported to be associated with NPC in previous reports.…”

“…Increasing evidence has indicated that metabolic disturbance could serve as a predictor for NPC. Various technologies, including gas chromatograph‐–mass spectrometry (GC–MS), proton nuclear magnetic resonance ([1H]‐NMR), and liquid chromatography‐high resolution mass spectrometry (LC‐HRMS) have been employed in serum metabolomics studies for the early diagnosis and pathogenesis of NPC 26–29 . Among the 181 metabolites significantly changed in the NPC serum, half belongs to lipids and lipid‐like molecules.…”