br Authorship br Disclosures br Introduction

Authorship
Disclosures
Introduction Esophageal cancer is the fourth most common cancer in China, with a total of 477,900 new cases and 375,000 deaths projected to occur in 2015, and it is more common in males than in females (Chen et al., 2016). The two major histological types of esophageal cancer, viz. esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), which are distinct entities affected by diverse risk profiles, are now experiencing a global epidemiologic shift in recent decades (Brown and Devesa, 2002; Alexandre et al., 2014; Rustgi and El-Serag, 2014). Remarkably, compared with the most prevalent EAC in the U.S. and many Western countries, ESCC is the purchase AM251 histological type in China, and accounts for over 90% of esophageal cancer cases (Torre et al., 2015; Arnold et al., 2015). Despite recent substantial advances in clinical diagnostic and therapeutic tools (Sawayama et al., 2014; Messager et al., 2017), esophageal cancer exhibits an extremely poor prognosis with the 5-year survival rate of around 20% in China, mainly because it grows aggressively and is often diagnosed at an advanced stage (Zeng et al., 2015; Tseng et al., 2015; Klein and Stoecklein, 2009). One of the practical choices to improve overall survival is the identification of easy-to-obtain markers with prognostic significance for esophageal cancer by formulating more targeted and effective management strategies for high risk patients, such as metabolic profiling markers (Yakoub et al., 2010). Large population-based studies have revealed that some metabolic factors such as obesity and diabetes are significant risk predictors for esophageal cancer, whereas the associated risk directions were not uniformly reported (Rustgi and El-Serag, 2014; Lindkvist et al., 2014; Lin et al., 2015; Alexandre et al., 2014). As for metabolic syndrome, several prospective studies have failed to identify its significant prediction for ESCC risk (Lin et al., 2015; Lindkvist et al., 2014). However, the prognostic prediction of metabolic risk factors has been reported only sparingly for esophageal cancer, except for a retrospective report by Wen et al. on the prognosis of preoperative metabolic syndrome among 596 patients with esophageal cancer (Wen et al., 2016). To our great surprise, they observed that the concomitance of metabolic syndrome before surgery was associated with better overall survival and tumor differentiation (Wen et al., 2016). This observation is somewhat counterintuitive based on what is known about the established relationship between metabolic syndrome and cancer risk (Esposito et al., 2012). Hence, a large prospective study is urgently needed to update our knowledge about the impact of metabolic syndrome on esophageal cancer prognosis. As an initial step toward meeting this need, we elicited a subset of data on esophageal cancer from the Fujian prospective investigation of cancer (FIESTA) study, and assessed the preoperative prediction of metabolic syndrome and its single components for esophageal cancer mortality. The FIESTA study initiated in January 2000 is an ongoing prospective cohort study of common digestive system tumors, including esophageal cancer, gastric cancer and colorectal cancer (Hu et al., 2016a,b; Hu et al., 2017; Peng et al., 2016), and the purport of this study is to identify preoperative prognostic risk factors for cancer-specific mortality, which will help pinpoint underlying targets to delay tumor progression and prolong the survival of cancer patients after surgery.
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Results
Discussion On the basis of 2396 ESCC patients who underwent three-field lymphadenectomy from the FIESTA study (Hu et al., 2016a,b; Hu et al., 2017; Peng et al., 2016), we assessed the gender-specific prediction of preoperative metabolic syndrome and its single components for esophageal cancer mortality over a 15-year follow-up period. The key finding of the present study is that preoperative metabolic syndrome was identified as a significant independent predictor of ESCC mortality in male patients, and this effect was largely mediated by glyeolipid metabolism disorder. In addition, the predictive utility of metabolic components, fasting blood glucose in particular, for ESCC mortality was contingent on TNM stage and regional LNM and was independent of obesity. To the best of our knowledge, this is so far the first prospective cohort study that has evaluated the preoperative prognosis of metabolic syndrome for esophageal cancer.