Biomarkers for detecting colorectal cancer non-invasively: DNA, RNA or proteins?

Table 4 Non-invasive volatile organic compounds and small metabolite biomarkers used for colorectal cancer detection

Study setting	Sample type	Marker type	Biomarker(s) and detection methods	Sensitivity (or its range)	Specificity (or its range)	Ref.
Case-control	Stool	VOCs	Hydrogen sulphide, Dimethylsulphide, Dimethyldisulphide, mlz 90 - detected by selected ion flow tube (SIFT) mass spectrometry (MS)	72.00%	78.00%	[94]
Case-control	Stool	VOCs	Propan-2-ol, 3-methylbutanoic acid - detected by gas chromatography (GC) and MS	87.90%	84.60%	[95]
Case-control	Stool	VOCs	Methyl mercaptan (increased) and hydrogen (decreased) – detected by GC	90.00%	57.70%	[96]
Case-control	Stool	VOCs	Pattern recognition technique - canine scent judgment	97.00%	99.00%	[97]
Case-control	Stool	VOCs	Pattern recognition technique (eNose Cyranose® 320)	85.00%	87.00%	[94]
Case-control	Stool	VOCs	Pattern recognition technique (SCENT A1)	95.00%	95.00%	[98]
Case-control	Urine	VOCs	Ion mobility spectroscopy technology (FAIMS)	88.00%	60.00%	[99]
Case-control	Urine	VOCs	Ion mobility spectroscopy technology (FAIMS)	63.00%	63.00%	[100]
Case-control	Urine	VOCs	Pattern recognition technique (eNose applied)	78.00%	79.00%	[99]
Case-control	Breath	VOCs	Pattern recognition technique - canine scent judgment	91.00%	99.00%	[97]
Case-control	Breath	VOCs	Acetone (increased), ethyl acetate (increased), ethanol (decreased) and 4-methyl octane (decreased) detected by GC-MS	85.00%	94.00%	[99]
Case-control	Breath	VOCs	Nonanal, decanal, 4-methyl-pentanone, 2-methylbutane, 4-methyloctane, 4-methylundecane, 2-methylpentane, methylcyclopentane, cycloxehane, methylcyclohexane, trimethyldecane-1,2-pentadiene, 1,3-dimethylbenzene, 1,4-dimethylbenzene – detected by GC-MS	86.00%	83.00%	[99]
Case-control	Stool	Magnetic resonance spectra	Magnetic resonance spectra patterns	85.20%	86.90%	[101]
Case-control	Stool	Small metabolites	Acetate – detected by proton magnetic resonance spectroscopy (PMRS)	94.70%	92.30%	[102]
Case-control	Stool	Small metabolites	Succinate – detected by PMRS	91.20%	93.50%	[102]
Case-control	Serum	Aromatic carboxylic acids	Benzoic acid – detected by CE-time of flight (TOF) MS	89.00%	82.00%	[103]
Case-control	Serum	Fatty acids	GTA-446 – detected by flow injection analysis MS	83.30%	84.80%	[104]
Case-control	Plasma	Amino acid metabolites	L-kynurenine – detected by high-performance liquid chromatography (HPLC)	85.20%	100.00%	[105]
Case-control	Plasma	Fatty acids	Decanoic acid – detected by CE-TOFMS	87.80%	80.00%	[106]
Case-control	Serum	Multiple metabolites	38 metabolites detected by GC-MS	85.00%	86.00%	[107]
Case-control	Serum	Phospholipids (sphingomyelins and phosphatidylcho-lines)	SM (34:1), PC (34:1), PC (34:2), PC (36:4), PC (36:2), PC (36:3) - detected by MS	♂77.3%; ♀80.8%	♂92.4%; ♀85.9%	[108]
Case-control	Serum	Unsaturated free fatty acids (panel)	C16:1, C18:3, C20:4, C22:6, all downregulated – detected by MS	93.80%	92.20%	[109]
Case-control	Serum	Amino acids (panel)	8 amino acids – detected by LC-MS/MS	65.00%	95.00%	[110]
Case-control	Serum	Amino acids, fatty acids, carbohydrates	13 metabolites – detected by LC-MS/MS	96.00%	80.00%	[111]
Case-control	Serum	Metabolite panel	2-hydroxy-butyrate, aspartic acid, kynurenine, cystamine – detected by GC-MS	83.10%	81.00%	[112]
Case-control	Serum	Lipid metabolites (panel)	Palmitic amide, oleamide, hexadecaneodioic acid, octadecanoic acid, eicosatrienoic acid, LPC(18:2), LPC(20:4), LPC(22:6), myristic acid, LPC(16:0) – detected by ion cyclotron resonance MS	98.10%	100.00%	[113]
Case-control	Serum	Panel of hydroxylated polyunsaturated ultra long-chain fatty acids	C28H46O4, C28H48O4 and C28H50O4, all downregulated – detected by LC-MS/MS and nuclear MR	75.00%	90.00%	[114]
Case-control	Serum	Multiple metabolites (panel)	11,14-eicosadienoic acid, 12a-hydroxy-3-oxocholadienic acid, 12-ketodeoxycholic acid, 12-keto-tetrahydro-leukotriene B4, 13-cis-retinoic acid, 1b-hydrocholic acid, 1-methylhistamine, 1-monopalmitin, 2,3-dihydroxybutanoic acid, 24-hydroxycalcitriol – detected by GC-TOFMS and UPLC-QTOFMS	83.70%	91.70%	[115]
Case-control	Plasma	Amino acids, fatty acids, carbohydrates	8 metabolites – detected by CT-TQMS	99.30%	93.80%	[116]
Case-control	Plasma	Choline-containing phospholipids (panel)	Total saturated lysophosphatidyl-cholines (LPCs), 18:2 LPC and sphingosylphosphorylcholine – detected by LC-MS/MS	88.30%	80.00%	[117]
Case-control	Plasma	Choline-containing phospholipids (panel)	Total saturated lysophosphatidyl-cholines (LPCs) and the difference between 18:2 LPC and 18:1 LPC – detected by LC-MS	82.00%	93.00%	[118]
Case-control	Dried blood	Amino acids and acylcarnitines (panel)	C16, Arg, C4/C8, C5/C3, Val, Phe/Tyr, Ala, C4/C3 – detected by direct infusion MS	81.20%	83.90%	[119]
Case-control	Urine	Polyamines	N1, N12-diacetylspermine – detected by ELISA	75.80%	96.00%	[120]
Case-control	Urine	Polyamines and amino acid metabolites	N1, N12-diacetylspermine and kynurenine – detected by LC-MS	80.00%	80.00%	[121]
Case-control	Urine	Amino acids and acetoacetate (panel)	Alanine, glutamine, aspartic acid and acetoacetate – detected by PMRS	87.50%	91.30%	[122]
Case-control	Urine	Nucleosides (panel)	5-hydroxymethyluracil and 8-oxo-7,8-dihydroguanine – detected by UPLC-MS/MS	78.60%	75.00%	[123]
Case-control	Urine	Nucleosides (panel)	Cytidine, 3-methylcitidine, 1-methyladenosine, 2-deoxyguanosine, adenosine, inosine – detected by HPLC-MS/MS	69.00%	98.00%	[124]
Case-control	Urine	Metabolite panel	Citrate, Hippurate, p-cresol, 2-aminobutyrate, myristate, putrescine and kynurenate - detected by UPLC-QTOFMS	97.50%	100%	[125]
Case-control	Urine	Nucleosides (panel)	Adenosine, N4-acetylcytidine, cytidine, guanosine, inosine, 1-methyladenosine, 1-methylguanosine, 1-methylinosine, 2-methylguanosine, 2,2-methylguanosine, N6-methyladenosine, uridine, 3-methyluridine+5-methyluridine, pseudouridine – detected by reverse phase HPLC	76.90%	90.40%	[126]
Case-control	Urine	Nucleosides (panel)	Adenosine, N4-acetylcytidine, cytidine, guanosine, inosine, 1-methyladenosine, 1-methylguanosine, 1-methylinosine, 2-methylguanosine, 2,2-methylguanosine, N6-methyladenosine, 5-methyluridine, pseudouridine, uridine – detected by column switching HPLC	71.00%	96.00%	[127]