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. 2022 Sep 8;9:934311. doi: 10.3389/fmolb.2022.934311

TABLE 1.

Selected characteristics of reviewed studies on ORL.

Author Years Sample size Biofluid Technique Biomarkers Candidates Results Comments
Increase (↑) or decrease (↓) biomarker concentration compared to the control group
Head and neck cancers
 Almadori et al. 2007 127 subjects: 50 patients with oral and pharyngeal squamous cell carcinomas and 77 healthy controls Saliva HPLC-MS Glutathione Glutathione ↑
 Sugimoto et al. 2010 158 subjects: 69 oral cancer patients and 89 healthy controls Saliva CE-TOF-MS Betaine; Isoleucine; Leucine; Phenylalanine; Tyrosine; Valine; Choline; Carnitine; Glycerophosphocholine; Cadaverine; Putrescine; Hypoxanthine; Ethanolamine; Trimethylamine; Tryptophan; Valine; Glutamic acid; Glutamine; Aspartate; Taurine; Lysine; Pyrroline hydroxycarboxylic acid; Pipecolic acid; Piperidine; Serine; β-alanine; Histidine Isoleucine ↑
Leucine ↑ Taurine ↑
Valine ↑ Tryptophan ↑
Putrescine ↑ Alanine ↑
Pipecolic acid ↑
Choline ↑
Glycerophosphocholine ↑
Histidine ↑ Carnitine ↑
Threonine ↑ Glutamate ↑
 Tiziani et al. 2009 15 subjects with oral cancer and 10 controls Serum 1H-NMR Valine, Ethanol, Lactate, Alanine, Acetate, Citrate, Phenylalanine, Tyrosine, Methanol, Formaldehyde; Formic acid; Glucose; Pyruvate; Acetone, Acetoacetate; 3-hydroxybutyrate; 2-hydroxybutyrate; Choline; Betaine; Dimethylglycine; Sarcosine; Asparagine; Ornithine Valine ↓ Ethanol ↓ The metabolomics profile of patients with oral cancer at the different stages of the disease was also evaluated
Lactate ↓ Alanine ↓ Acetate ↓ Citrate ↓ Phenylalanine ↓
Tyrosine ↓ Methanol ↓ Formaldehyde ↓ Formic acid ↓ Glucose ↑
Pyruvate ↑ Acetone ↑ Acetoacetate ↑ 3-hydroxybutyrate ↑
2-hydroxybutyrate↑ Choline ↑ Betaine ↑ Dimethylglycine ↑ Sarcosine ↑ Asparagine ↑ Ornithine ↑
 Yonezawa et al. 2013 Serum and Tissue GC-MS Glucose; Ribulose; Methionine; Ketoisoleucine; Histidine, Aspartic acid, Glutamic acid, Asparagine, Lysine, Serine, Methionine; Alanine In serum:
Glucose ↑ Ribulose ↑
Methionine ↓ Ketoisoleucine ↓
In tissue:
Histidine ↑
Aspartic acid ↑
Glutamic acid ↑ Asparagine ↑ Lysine ↑ Serine ↑ Methionine ↑ Alanine ↑ Glucose ↓
Allergic rinitis
 Ma et al. 2020 28 allergic rhinitis patients and 28 healthy controls Serum UPLC-QTOF-MS Bilirubin; Hypoxanthine; 15(S)-HETE*; Hexadecenoic acid; Urate; **13(S)-HPODE; Leukotriene D4; Stercobilinogen; N-succinyl-diaminopimelic acid; Chlorophyll b Bilirubin ↑ *15(S)-hydroxyeicosatetraenoic acid; **13(S)-hydroperoxyoctadecadienoic acid
Hypoxanthine ↑
15(S)-HETE ↑ Hexadecenoic acid ↑
Urate ↑ The metabolites were mainly involved in pathways of porphyrin and chlorophyll metabolism, arachidonic acid metabolism, and purine metabolism
Leukotriene D4 ↓ Stercobilinogen ↓
N-succinyl-diaminopimelic acid ↓ Chlorophyll b ↓
 Zheng et al. 2021 73 patients with allergic rhinitis: 35 and 38 patients with single or double-mite subcutaneous immunotherapy respectively. Serum UPLC-QTOF-MS *HETE; **HEPE; In SM-SCIT and DM-SCIT patients: *15(S)- hydroxyeicosatetraenoic acid
***HODE; *HETE ↓ **HEPE ↓ **5(S)-HETE, 12(S)- hydroxyeicosapentaenoic acid
11(S)-HETE; 8(S)-HETE; 5(S)-HEPE; Arachidonic acid; Eicosapentaenoic acid (EPA); 9(S)- hydroperoxylinoleic acid (HPODE) ***HODE ↓ ***13- hydroxyoctadecadienoicacid
In DM-SCIT patients:
11(S)-HETE ↓
8(S)-HETE ↓ 5(S)-HEPE↓ Arachidonic acid↓ Eicosapentaenoic acid (EPA) ↓
In SM-SCIT patients:
HPODE ↑
 Yuan et al. 2022 28 patients with allergic rhinitis Serum UPLC-QTOF-MS 26 altered metabolites between: Prostaglandin E2 ↑ Prostaglandin H2 ↑ Prostaglandin D2 ↑ Thromboxane A2 ↑ 20-Hydroxy-leukotriene B4 ↑ Linoleic acid ↑ 9,10-Epoxyoctadecenoic acid ↑ 12,13-EpOME ↑ Paraxanthine ↑ Theobromine ↑ The metabolites were mainly involved in linoleic acid metabolism, arachidonic acid metabolism and caffeine metabolism
15 healthy individuals Prostaglandin E2; Prostaglandin H2; Prostaglandin D2; Thromboxane A2; 20-Hydroxy-leukotriene B4; Linoleic acid; 9,10-Epoxyoctadecenoic acid; 12,13-EpOME; Paraxanthine; Theobromine;
Hearing loss
 Trinh et al. 2019 19 patients affected by sensorineural hearing loss: Perilyph fluid LC-MS/MS N-acetylneuraminate, Glutaric acid, l-cystine, 2-methylpropanoate, Butanoate, Xanthine, l-histidine, S-lactate, 4-hydroxy-l-proline, Serotonin, 2-deoxy-D-Glucose, N-acetyl-l-Alanine; l-proline; Taurine Patients >12 years: N-acetylneuraminate ↑
10 patients ≤12 years
9 patients >12 years
Meniere’s disease
 Di Bernardino F. et al. 2018 26 patients with definite unilateral MD: 14 patients symptomatic and 12 asymptomatic 20 healthy volunteers Urine Double sugar test and fecal calprotectin Lactulose and mannitol absorption In the symptomatic MD symptomatic: Lactulose and mannitol absorption ↑
Fecal calprotectin (FC) FC ↑
Obstructive sleep apnea (OSA)
 Xu et al. 2016 60 OSA patients Urine UPLC-QTOF-MS coupled with GC-TOF-MS 3-hydroxybutyric acid; 3-methyl-3-hydroxybutyric acid; 4-hydroxypentenoic acid; Lactic acid; Myoinositol; 2-Butenedioic acid OSA patients compared to SS and control groups:
30 simply snored patients (SS) 3-hydroxybutyric acid↑ 3-methyl-3-hydroxybutyric acid ↑ 4-hydroxypentenoic acid ↑
30 controls OSA patients compared to control groups: lactic acid ↑ myoinositol ↑ 2-butenedioic acid ↓
 Lebkuchen et al. 2018 37 patients with OSA Plasma MALDI-TOF-MS Glycerophosphoethanolamines (PE-35:1); Lyso-phosphocholines (LPC-27:1); Sphingomyelin (SM-d18:1/12:0); Glutamic acid, Deoxy sugar; Arachidonic acid; Diacylglycerols (DAG); Glycerophosphocholines (PC); Glycerophosphates (PA) PE-35:1 ↑ LPC-27:1 ↑
SM-d18:1/12:0 ↑
Glutamic acid ↑
16 controls Deoxy sugar ↑
Arachidonic acid ↑
DAG ↓ PC ↓ PA ↓
 Pinilla et al. 2022 206 subjects: 142 OSA subjects [apnea-hypopnea index ≥15 events/hour after polysomnography (PSG)] Serum UPLC-QTOF-MS Glycerophospholipid (cardiolipin (CL); Phosphatidylcholine (PC-P (36:4)); Phosphatidylethanolamine (PE)); Sterols (bile acids); Oxylipids; 25-Cinnamoyl vulgaroside; Glycocholic acid; Bilirubin CL ↑ PC-P (36:4) ↑ PE ↑ Sterols (bile acids) ↑ Oxylipids ↑ The metabolites were mainly involved in glycerophospholipid metabolism, primary bile acid biosynthesis, linoleic acid metabolism, α-linolenic acid metabolism and glycosylphosphatidylinositol acid metabolism
Effect of CPAP treatment on the circulating profile of OSA patients:
25-Cinnamoyl vulgaroside ↑ Glycocholic acid ↑ Bilirubin ↑
 Xu et al. 2018 30 pediatric subjects with OSA compared to a control group Urine UPLC-Q-TOF-MS coupled with GC-TOF-MS Carbohydrates; Amino acid; Metabolites of microbial origin; Vitamins; Citrulline; Ornithine; 7-Methylguanine; Adenine; Uridine; 3,4,5-Trihydroxypentanoic acid; Quinic acid; Glycerol phosphate; Butanoate; Glucuronic acid; 2-Methylacetoacetic acid; 3-Methyl-2-pentenedioic acid; 3-pyridylacetic acid; Methylcitric acid; Oxalic acid Increase in biomarker candidates in pediatric OSA patients ↑ The metabolites were involved in amino acid metabolism, carbohydrate metabolism, microbial metabolism, vitamin metabolism, ornithine cycle, nucleic acid metabolism, fatty acid metabolism, butanoate metabolism, and bilirubin metabolism
Noise trauma
 Ji et al. 2019 CBA/J mice (aged 8–12 weeks) subject to exposure to octave band noise (8–16 kHz) Tissue UHPLC-QqQ coupled with LC-MS/MS Nucleotides; Cofactors; Carbohydrates; Glutamate; Amino acids; Cytosine; N-methyl-L-glutamate; L-methionine; L-arginine Nucleotides ↑ Cofactors ↑ Carbohydrates ↑ Glutamate ↑ The metabolites were involved in metabolism of alanine, aspartate, purine, glutamine and glutamate, and the metabolism of phenylalanine, tyrosine and tryptophan
Amino acids ↓
Change in metabolites with respect to the intensity and duration of noise exposure:
Cytosine ↑ N-methyl-L-glutamate ↑
L-methionine ↓
L-arginine ↓
 Miao et al. 2021 62 NIHL patients Plasma UHPLC-Q-TOF MS Homodeoxycholic acid; Quinolacetic acid; 3,4-dihydroxymandelic acid; PE (15: 0/20: 2 (11Z, 14Z)); PC (15: 0/18: 1 (11Z)); PI (O-20: 0/18: 0) Homodeoxycholic acid ↑ Quinolacetic acid ↑ 3,4-dihydroxymandelic acid ↑ Autophagy pathway was particularly involved in patients with NIHL
62 Controls PE ↓ PC ↓ PI ↓