Abstract
Extranodal extension (ENE) is an independent adverse prognostic factor in oral squamous cell carcinoma (OSCC), and is difficult to identify preoperatively. We aimed to discover biomarkers for high risk patients with ENE. Tandem tissue, plasma, and urine samples of 110 patients with OSCC were investigated through 600-MHz nuclear magnetic resonance (NMR) metabolomics analysis. We found that the levels of creatine, creatine phosphate, glycine, and tyramine in plasma significantly decreased in stage IV ENE positive OSCC compared with stage IV ENE negative OSCC. To understand the underlying mechanism behind the alteration of plasma metabolites, our tissue analysis revealed that the carnitine level significantly increased in tumors but significantly decreased in the adjacent normal tissue in advanced stage OSCC, in addition to decreased levels of alanine and pyruvate in tumor tissues. The global metabolomics analysis on tumor tissues also showed that stage IV tumors with an ENE positive status demonstrated higher levels of aspartate, butyrate, carnitine, glutamate, glutathione, glycine, glycolate, guanosine, and sucrose but lower levels of alanine, choline, glucose, isoleucine, lactate, leucine, myo-inositol, O-acetylcholine, oxypurinol, phenylalanine, pyruvate, succinate, tyrosine, valine, and xanthine than tumors with an ENE negative status. We concluded that metabolomics alterations in tumor tissues correspond to an increase in the tumor stage and are detectable in plasma samples. Metabolomic alterations of OSCC can serve as potential diagnostic markers and predictors of ENE in patients with stage IV OSCC.
Highlights
More than 300,000 patients are annually estimated to have oral squamous cell carcinoma (OSCC) worldwide, and the mortality rate is 48%
We enrolled patients treated from December 2014 to November 2017, according to the American Joint Committee on Cancer (AJCC) Staging System, seventh edition
We demonstrated that the levels of creatine, creatine phosphate, glycine, and tyramine in plasma significantly decreased in stage IV extranodal extension (ENE) positive OSCC compared with stage IV ENE negative OSCC
Summary
More than 300,000 patients are annually estimated to have oral squamous cell carcinoma (OSCC) worldwide, and the mortality rate is 48%. It is an aggressive cancer that can infiltrate and metastasize highly, with a reported five-year survival rate of approximately 50% [1,2]. Despite new treatments, there has been no marked improvement in five-year survival rates over the past few decades [3]. In OSCC, the nodal staging recommendations have upstaged extranodal extension (ENE) of metastatic nodes, which has been reported as a high-risk adverse feature associated with worse survival [5]. The presence of ENE is an independent adverse prognostic factor in OSCC [6,7], and it significantly decreases survival [8,9] as well as locoregional and distant control [10,11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
