Volatilomic insight of head and neck cancer via the effects observed on saliva metabolites

Abstract

Head and neck cancer (HNC) is a heterogeneous malignant disease with distinct global distribution. Metabolic adaptations of HNC are significantly gaining clinical interests nowadays. Here, we investigated effects of HNC on differential expression of volatile metabolites in human saliva. We applied headspace solid phase microextraction coupled with gas chromatography-mass spectrometry analysis of saliva samples collected from 59 human subjects (HNC − 32, Control − 27). We identified and quantified 48 volatile organic metabolites (VOMs) and observed profound effects of HNC on these metabolites. These effects were VOM specific and significantly differed in the biologically comparable healthy controls. HNC induced changes in salivary VOM composition were well attributed to in vivo metabolic effects. A panel of 15 VOMs with variable importance in projection (VIP) score >1, false discovery rate (FDR) corrected p-value < 0.05 and log2 fold change (log2 FC) value of ≥0.58/≤−0.58 were regarded as discriminatory metabolites of pathophysiological importance. Afterwards, receiver operator characteristic curve (ROC) projected certain VOMs viz., 1,4-dichlorobenzene, 1,2-decanediol, 2,5-bis1,1-dimethylethylphenol and E-3-decen-2-ol with profound metabolic effects of HNC and highest class segregation potential. Moreover, metabolic pathways analysis portrayed several dysregulated pathways in HNC, which enhanced our basic understanding on salivary VOM changes. Our observations could redefine several known/already investigated systemic phenomenons (e.g. biochemical pathways). These findings will inspire further research in this direction and may open unconventional avenues for non-invasive monitoring of HNC and its therapy in the future.

A Literature Review of the Potential Diagnostic Biomarkers of Head and Neck Neoplasms

“…This decrease of undecane is in contrast to an increase found in breath in HNSCC ( 40 ) and patients with PTC ( 46 ). Furthermore, saliva analysis of the single VOCs 1,4-dichlorobenzene, 1,2-decanediol, 2,5-bis1,1-dimethylethylphenol, and E-3-decen-2-ol allowed to discriminate HNSCC patients from controls with a sensitivity and specificity between 80–100% and 80–100%, respectively ( 51 ), again being different to VOCs found in exhaled breath and urine ( 50 ).…”

Unravelling the Potential of Salivary Volatile Metabolites in Oral Diseases. A Review

“…Taware et al applied the same principle to oral cancer and analysed the salivary volatile composition of a small cohort of 32 oral cancer patients and 27 controls. The authors reported that the volatiles 1,4-dichlorobenzene, 1,2-decanediol, 2,5-bis1,1-dimethylethylphenol and E-3-decen-2-ol were significantly associated with the malignant disease, possessing an excellent discriminatory potential [87].…”

“…As the name suggests, in this methodology the volatile metabolites are loaded in the GC column and the separated metabolites then detected by MS. The sample volatiles can be preconcentrated using various approaches such as Solid Phase Micro Extraction (SPME) or Needle Trap Micro Extraction (NTME), desorbed in the GC, separated and detected [87,95,97]. The samples that are not volatile under normal conditions can be derivatized to make the metabolites thermostable and gaseous at higher temperature.…”

Introductory Chapter: Insight into the OMICS Technologies and Molecular Medicine

“…Omics-based approaches have been significantly improved recently with the addition of novel concepts such as exposome/exposomics, the study of the environmental exposure, to unravel the role of the environment in human diseases. Furthermore, the addition of adductomics, the study of compounds that bind DNA and cause damage and mutations, and volatilomics, the study of volatile organic compounds to the metabolomics/lipidomics analysis for comprehensive research of the metabolome have been newly emerging [2,10,11]. Exposome is a person's total lifestyle and environmental exposures, which is not well understood yet.…”