Meanwhile to our knowledge this is the

Meanwhile, to our knowledge, this is the first report of B-cell function gene diprenorphine profile in a large cohort of Chinese DLBCL patients treated with R-CHOP. Presenting with similar incidence as Western population, B-cell function gene mutations were closely related to DLBCL progression, particularly those involved in TLRs and TNFR pathways, resulting in aberrant activation of NF-κB cascade and resistance to immunochemotherapy in DLBCL (Davis et al., 2010). Clinical trials simply targeting NF-κB have been attempted recent years in patients but most of the results were disappointing (Offner et al., 2015; Leonard et al., 2016). Here we provided evidence that, among mutations involving NF-κB activation, the BCRs pathway, rather than the TLRs and TNFR pathway, was inhibited by rituximab, in consistence with previous basic study (Kheirallah et al., 2010). Thus, the presence of BCR/NF-κB mutations may be more precise in guiding the response to rituximab and referred as a major consideration on rituximab consolidation. As for the TLRs and TNFR related gene mutations, they reflected poor therapeutic response and represented actionable targets for new therapeutic approaches like the BTK inhibitor ibrutinib (Wilson et al., 2015) and IRAK1/4 inhibitor for MYD88 (Li et al., 2015), as well as proteasome inhibitors bortezomib and carfilzomib for TNFAIP3 (Shembade et al., 2010).

Funding
This study was supported, in part, by research funding from the National Natural Science Foundation of China (81325003, 81520108003, 81670716 and 81201863), the Shanghai Commission of Science and Technology (14430723400, 14140903100 and 16JC1405800), Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support (20152206 and 20152208), Multi-center clinical research project by Shanghai Jiao Tong University School of Medicine (DLY201601), SMC-Chen Xing Scholars Program, Chang Jiang Scholars Program, Collaborative Innovation Center of Systems Biomedicine and the Samuel Waxman Cancer Research Foundation.

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 dominant 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.