Plasma metabolomics of oral squamous cell carcinomas based on NMR and MS approaches provides biomarker identification and survival prediction

Abstract

Metabolomics has proven to be an important omics approach to understand the molecular pathways underlying the tumour phenotype and to identify new clinically useful markers. The literature on cancer has illustrated the potential of this approach as a diagnostic and prognostic tool. The present study aimed to analyse the plasma metabolic profile of patients with oral squamous cell carcinoma (OSCC) and controls and to compare patients with metastatic and primary tumours at different stages and subsites using nuclear magnetic resonance and mass spectrometry. To our knowledge, this is the only report that compared patients at different stages and subsites and replicates collected in diverse institutions at different times using these methodologies. Our results showed a plasma metabolic OSCC profile suggestive of abnormal ketogenesis, lipogenesis and energy metabolism, which is already present in early phases but is more evident in advanced stages of the disease. Reduced levels of several metabolites were also associated with an unfavorable prognosis. The observed metabolomic alterations may contribute to inflammation, immune response inhibition and tumour growth, and may be explained by four nonexclusive views—differential synthesis, uptake, release, and degradation of metabolites. The interpretation that assimilates these views is the cross talk between neoplastic and normal cells in the tumour microenvironment or in more distant anatomical sites, connected by biofluids, signalling molecules and vesicles. Additional population samples to evaluate the details of these molecular processes may lead to the discovery of new biomarkers and novel strategies for OSCC prevention and treatment.

Salivary metabolomic identification of biomarker candidates for oral melanoma and oral squamous cell carcinoma in dogs

“… 52 Sarcosine has been implicated in promoting the malignant proliferation of benign prostate cancer cells, making it a potential marker for assessing prostate cancer when identified in serum and urine samples. 14 , 53 Plasma nuclear magnetic resonance (NMR) metabolic profiles have identified increased sarcosine concentrations in OSCC patients compared with controls 15 However, it was found at a low concentration in saliva of OSCC of humans compared with healthy controls, with an unknown mechanism. 54 In tumor studies of dogs, sarcosine exhibits significant downregulation in dogs with urothelial carcinoma of the bladder compared with those with urolithiasis, regardless of the presence of urinary tract infection.…”

“… 10 In recent years, salivary metabolomics has emerged as a diagnostic tool for various cancers in humans, including oral, breast, pancreatic, and prostatic cancers. 11 , 12 , 13 , 14 , 15 Aberrant metabolites in aminoacyl transfer RNA (tRNA) biosynthesis, arginine biosynthesis and metabolism, lysine degradation, histidine metabolism, and proline metabolism have been identified from precancerous stages in humans with OSCC. 16 One study demonstrated the ability of the combination of S‐adenosylmethionine and pipecolate from saliva samples to distinguish patients with oral cancers from healthy controls.…”