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Citation Information
Int J Biol Markers. 2018 Aug;33(3):314-320. doi: 10.1177/1724600818778754. Epub 2018 Jun 13.
Cortisol, cortisone, and 4-methoxyphenylacetic acid as potential plasma biomarkers for early detection of non-small cell lung cancer.
Xiang C, Jin S, Zhang J, Chen M,, Xia Y,, Shu Y, Guo R.
Analytical methods | |||||
|---|---|---|---|---|---|
| Comparative study | #1 | #2 | #3 | #4 | |
| Chromatography | LC | LC | LC | LC | |
| Ion source | ESI | ESI | ESI | ESI | |
| Positive/Negative mode | both | both | both | both | |
| Mass analyzer | LTQ-FT | LTQ-FT | LTQ-FT | LTQ-FT | |
| Identification level | – | – | – | – | |
Sample information | |||||
|---|---|---|---|---|---|
| Comparative study | #1 | #2 | #3 | #4 | |
| Country | China | China | China | China | |
| Specimen | plasma | plasma | plasma | plasma | |
| Marker function | diagnosis | diagnosis | diagnosis | diagnosis | |
| Participants(Case) | Cancer type | adenocarcinoma | adenocarcinoma | squamous cell carcinoma | squamous cell carcinoma |
| Stage | I, II, III, IV | I, II, III, IV | I, II, III, IV | I, II, III, IV | |
| Number | 28 | 24 | 25 | 22 | |
| Gender (M,F) | 16, 12 | 10, 14 | 21, 4 | 16, 6 | |
| Mean age (range) (M,F) | 59 (44-80) | 59 (43-71) | 59.8 (43-83) | 60.5 (42-73) | |
| Smoking status | former, current, non-smoker | former, current, non-smoker | former, current, non-smoker | former, current, non-smoker | |
| Participants(Control) | Type | healthy | healthy | healthy | healthy |
| Number | 56 | 56 | 56 | 56 | |
| Gender (M,F) | 35, 21 | 35, 21 | 35, 21 | 35, 21 | |
| Mean age (range) (M,F) | 58 (47-80) | 59 (42-79) | 58 (47-80) | 59 (42-79) | |
| Smoking status | former, current, non-smoker | former, current, non-smoker | former, current, non-smoker | former, current, non-smoker | |
Data processing and metabolite identification | |
|---|---|
| Data processing software | Analyst software |
| Database search | – |
Statistical analysis | |
|---|---|
| Differential analysis method | independent sample t-tests, OPLS-DA |
| Classification method | – |
| Survival analysis method | – |
Lung cancer-related metabolites identified in the paper
| Metabolite | Author-emphasized biomarkers | Mean concentration (case) | Mean concentration (control) | Fold change (case/control) | P-value | FDR | VIP |
|---|---|---|---|---|---|---|---|
| testosterone | – | – | – | 31.84 | 3.26e-15 | – | 2.14 |
| tetradecanedioic acid | – | – | – | 26.60 | 1.18e-18 | – | 1.56 |
| dodecanoic acid | – | – | – | 24.15 | 8.67e-24 | – | 2.10 |
| testosterone | – | – | – | 23.37 | 4.11e-09 | – | 1.43 |
| tetradecanedioic acid | – | – | – | 21.20 | 5.23e-18 | – | 1.16 |
| tetradecanedioic acid | – | – | – | 20.99 | 6.62e-17 | – | 1.80 |
| palmitoyl-Dl-carnitine chloride free | – | – | – | 19.57 | 1.42e-23 | – | 2.02 |
| indoleacetic acid | – | – | – | 19.57 | 3.84e-19 | – | 1.27 |
| cortisone | V | – | – | 16.72 | 1.12e-23 | – | 2.32 |
| palmitoyl-Dl-carnitine chloride free | – | – | – | 14.57 | 2.85e-20 | – | 2.20 |
| cortisol | V | – | – | 14.57 | 1.82e-25 | – | 2.52 |
| palmitoyl-Dl-carnitine chloride free | – | – | – | 13.22 | 3.01e-20 | – | 1.87 |
| sodium glycodeoxycholate bioxtra | – | – | – | 12.84 | 7.62e-10 | – | 1.65 |
| hexadecanedioic Acid | – | – | – | 11.77 | 6.06e-20 | – | 1.93 |
| indoleacetic acid | – | – | – | 11.54 | 2.90e-17 | – | 1.81 |
| tetradecanedioic acid | – | – | – | 11.28 | 6.47e-16 | – | 1.34 |
| cortisone | V | – | – | 11.26 | 4.30e-22 | – | 2.23 |
| indoleacetic acid | – | – | – | 10.55 | 2.53e-17 | – | 1.47 |
| sodium glycodeoxycholate bioxtra | – | – | – | 9.34 | 6.04e-08 | – | 1.34 |
| dodecanoic acid | – | – | – | 9.24 | 4.67e-19 | – | 1.83 |
| octadecanedioic acid | – | – | – | 9.22 | 3.51e-14 | – | 1.66 |
| cortisol | V | – | – | 8.87 | 1.09e-25 | – | 2.18 |
| hexadecanedioic Acid | – | – | – | 8.70 | 3.94e-16 | – | 2.00 |
| cortisone | V | – | – | 8.68 | 4.12e-20 | – | 2.55 |
| testosterone | – | – | – | 8.55 | 7.16e-09 | – | 1.64 |
| hexadecanedioic Acid | – | – | – | 8.31 | 6.61e-17 | – | 1.70 |
| indoleacetic acid | – | – | – | 8.14 | 4.72e-16 | – | 2.03 |
| octadecanedioic acid | – | – | – | 6.53 | 7.27e-14 | – | 1.89 |
| cortisol | V | – | – | 6.36 | 1.52e-23 | – | 2.42 |
| cuminaldehyde | – | – | – | 6.11 | 4.93e-14 | – | 1.99 |
| trans-ferulic acid | – | – | – | 5.97 | 3.06e-10 | – | 1.30 |
| dodecanoic acid | – | – | – | 5.89 | 4.94e-18 | – | 2.14 |
| cortisol | V | – | – | 5.84 | 9.08e-21 | – | 2.58 |
| octadecanedioic acid | – | – | – | 5.74 | 7.63e-13 | – | 1.87 |
| hexadecanedioic Acid | – | – | – | 5.55 | 9.15e-17 | – | 2.06 |
| indoleacrylic acid | – | – | – | 5.13 | 7.21e-07 | – | 1.26 |
| trans-ferulic acid | – | – | – | 5.11 | 4.93e-08 | – | 1.67 |
| 4-methylcatechol | – | – | – | 4.75 | 4.40e-11 | – | 1.75 |
| 4-methylcatechol | – | – | – | 4.72 | 3.23e-10 | – | 2.05 |
| indoleacrylic acid | – | – | – | 4.54 | 1.33e-05 | – | 1.43 |
| trans-ferulic acid | – | – | – | 4.47 | 2.13e-08 | – | 1.46 |
| trans-ferulic acid | – | – | – | 4.45 | 3.38e-07 | – | 1.39 |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | 4.38 | 7.30e-09 | – | 1.69 |
| palmitoyl-Dl-carnitine chloride free | – | – | – | 4.22 | 9.92e-17 | – | 1.90 |
| cortisone | V | – | – | 4.13 | 1.49e-17 | – | 2.15 |
| testosterone | – | – | – | 4.00 | 3.05e-04 | – | 1.29 |
| sodium glycodeoxycholate bioxtra | – | – | – | 3.96 | 6.02e-07 | – | 1.10 |
| octadecanedioic acid | – | – | – | 3.91 | 8.90e-11 | – | 1.44 |
| L-aspartyl-L-phenylalanine | – | – | – | 3.86 | 4.89e-08 | – | 1.36 |
| indoleacrylic acid | – | – | – | 3.50 | 1.34e-07 | – | 1.62 |
| dodecanoic acid | – | – | – | 3.31 | 9.21e-16 | – | 1.48 |
| cuminaldehyde | – | – | – | 3.21 | 3.40e-07 | – | 1.30 |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | 3.13 | 1.93e-06 | – | 1.74 |
| cuminaldehyde | – | – | – | 3.09 | 8.79e-12 | – | 1.22 |
| sodium glycodeoxycholate bioxtra | – | – | – | 2.98 | 7.92e-06 | – | 1.17 |
| 4-methylcatechol | – | – | – | 2.83 | 2.88e-07 | – | 1.88 |
| indoleacrylic acid | – | – | – | 2.71 | 5.83e-05 | – | 1.21 |
| 4-methylcatechol | – | – | – | 2.70 | 2.05e-06 | – | 1.51 |
| cuminaldehyde | – | – | – | 2.68 | 7.32e-07 | – | 1.34 |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | 2.65 | 1.13e-07 | – | 1.49 |
| L-aspartyl-L-phenylalanine | – | – | – | 2.17 | 4.64e-05 | – | 1.08 |
| L-aspartyl-L-phenylalanine | – | – | – | 1.99 | 1.12e-05 | – | 1.16 |
| L-aspartyl-L-phenylalanine | – | – | – | 1.99 | 1.19e-04 | – | 1.05 |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | 1.98 | 1.47e-05 | – | 1.39 |
| DL-glyceraldehyde | – | – | – | 0.61 | 5.47e-06 | – | 2.13 |
| DL-glyceraldehyde | – | – | – | 0.60 | 4.24e-08 | – | 1.99 |
| DL-glyceraldehyde | – | – | – | 0.56 | 2.56e-06 | – | 1.81 |
| DL-glyceraldehyde | – | – | – | 0.53 | 6.71e-08 | – | 2.25 |
| transtrans-farnesol | – | – | – | 0.47 | 4.75e-05 | – | 1.58 |
| 2,3-dihydroxypropyl decanoate | – | – | – | 0.45 | 3.82e-10 | – | 1.90 |
| 2,3-dihydroxypropyl decanoate | – | – | – | 0.45 | 3.83e-09 | – | 1.69 |
| 2,3-dihydroxypropyl decanoate | – | – | – | 0.43 | 1.09e-07 | – | 2.19 |
| transtrans-farnesol | – | – | – | 0.35 | 1.86e-08 | – | 1.85 |
| octadecanamide | – | – | – | 0.35 | 2.08e-07 | – | 1.90 |
| transtrans-farnesol | – | – | – | 0.32 | 3.16e-08 | – | 1.80 |
| 2,3-dihydroxypropyl decanoate | – | – | – | 0.32 | 1.56e-07 | – | 2.08 |
| 2-methoxycinnamic acid | – | – | – | 0.29 | 9.13e-08 | – | 1.52 |
| octadecanamide | – | – | – | 0.29 | 1.60e-08 | – | 2.34 |
| serotonin hydrochloride | – | – | – | 0.28 | 1.43e-08 | – | 1.36 |
| transtrans-farnesol | – | – | – | 0.27 | 1.48e-06 | – | 1.89 |
| 2-methoxycinnamic acid | – | – | – | 0.26 | 1.18e-06 | – | 2.25 |
| retinoic acid | – | – | – | 0.22 | 1.22e-06 | – | 2.01 |
| dehydroepiandrosterone | – | – | – | 0.22 | 2.75e-08 | – | 1.66 |
| dehydroepiandrosterone | – | – | – | 0.21 | 1.93e-08 | – | 1.59 |
| serotonin hydrochloride | – | – | – | 0.20 | 3.02e-10 | – | 1.65 |
| homovanillic acid | – | – | – | 0.18 | 3.26e-07 | – | 1.72 |
| serotonin hydrochloride | – | – | – | 0.18 | 2.67e-07 | – | 1.84 |
| 2-methoxycinnamic acid | – | – | – | 0.18 | 9.72e-09 | – | 1.94 |
| retinoic acid | – | – | – | 0.17 | 1.76e-09 | – | 2.04 |
| 2-methoxycinnamic acid | – | – | – | 0.16 | 9.22e-10 | – | 1.57 |
| octadecanamide | – | – | – | 0.15 | 5.82e-16 | – | 2.74 |
| dehydroepiandrosterone | – | – | – | 0.14 | 4.03e-12 | – | 2.06 |
| dehydroepiandrosterone | – | – | – | 0.13 | 2.45e-07 | – | 1.94 |
| octadecanamide | – | – | – | 0.13 | 1.46e-17 | – | 3.42 |
| 4-methoxyphenylacetic acid | V | – | – | 0.12 | 1.69e-13 | – | 2.27 |
| homovanillic acid | – | – | – | 0.11 | 1.66e-07 | – | 2.05 |
| retinoic acid | – | – | – | 0.11 | 1.21e-10 | – | 1.50 |
| 3,4,5-trimethoxycinnamic acid | – | – | – | 0.10 | 7.72e-16 | – | 1.88 |
| homovanillic acid | – | – | – | 0.09 | 8.52e-11 | – | 1.92 |
| homovanillic acid | – | – | – | 0.09 | 2.46e-11 | – | 1.77 |
| 4-methoxyphenylacetic acid | V | – | – | 0.08 | 7.77e-13 | – | 2.07 |
| serotonin hydrochloride | – | – | – | 0.08 | 8.19e-14 | – | 2.00 |
| 3,4,5-trimethoxycinnamic acid | – | – | – | 0.07 | 4.44e-15 | – | 1.59 |
| 4-methoxyphenylacetic acid | V | – | – | 0.06 | 9.24e-14 | – | 2.05 |
| 4-methoxyphenylacetic acid | V | – | – | 0.05 | 9.34e-13 | – | 2.65 |
| retinoic acid | – | – | – | 0.05 | 4.47e-07 | – | 1.33 |
| 1-palmitoyl-palmitoyl | – | – | – | 0.04 | 7.52e-15 | – | 1.94 |
| 1-palmitoyl-palmitoyl | – | – | – | 0.04 | 3.80e-13 | – | 1.79 |
| 3,4,5-trimethoxycinnamic acid | – | – | – | 0.03 | 4.97e-15 | – | 2.64 |
| 1-palmitoyl-palmitoyl | – | – | – | 0.03 | 2.57e-13 | – | 2.12 |
| 1-palmitoyl-palmitoyl | – | – | – | 0.03 | 6.74e-12 | – | 1.92 |
| 3,4,5-trimethoxycinnamic acid | – | – | – | 0.03 | 1.32e-16 | – | 2.07 |
| Metabolite | Author-emphasized biomarkers | Cutoff value | AUROC (95%CI) | Sensitivity (%) | Specificity (%) | Accuracy (%) |
|---|---|---|---|---|---|---|
| testosterone | – | – | – | – | – | – |
| tetradecanedioic acid | – | – | – | – | – | – |
| dodecanoic acid | – | – | – | – | – | – |
| testosterone | – | – | – | – | – | – |
| tetradecanedioic acid | – | – | – | – | – | – |
| tetradecanedioic acid | – | – | – | – | – | – |
| palmitoyl-Dl-carnitine chloride free | – | – | – | – | – | – |
| indoleacetic acid | – | – | – | – | – | – |
| cortisone | V | – | – | – | – | – |
| palmitoyl-Dl-carnitine chloride free | – | – | – | – | – | – |
| cortisol | V | – | – | – | – | – |
| palmitoyl-Dl-carnitine chloride free | – | – | – | – | – | – |
| sodium glycodeoxycholate bioxtra | – | – | – | – | – | – |
| hexadecanedioic Acid | – | – | – | – | – | – |
| indoleacetic acid | – | – | – | – | – | – |
| tetradecanedioic acid | – | – | – | – | – | – |
| cortisone | V | – | – | – | – | – |
| indoleacetic acid | – | – | – | – | – | – |
| sodium glycodeoxycholate bioxtra | – | – | – | – | – | – |
| dodecanoic acid | – | – | – | – | – | – |
| octadecanedioic acid | – | – | – | – | – | – |
| cortisol | V | – | – | – | – | – |
| hexadecanedioic Acid | – | – | – | – | – | – |
| cortisone | V | – | – | – | – | – |
| testosterone | – | – | – | – | – | – |
| hexadecanedioic Acid | – | – | – | – | – | – |
| indoleacetic acid | – | – | – | – | – | – |
| octadecanedioic acid | – | – | – | – | – | – |
| cortisol | V | – | – | – | – | – |
| cuminaldehyde | – | – | – | – | – | – |
| trans-ferulic acid | – | – | – | – | – | – |
| dodecanoic acid | – | – | – | – | – | – |
| cortisol | V | – | – | – | – | – |
| octadecanedioic acid | – | – | – | – | – | – |
| hexadecanedioic Acid | – | – | – | – | – | – |
| indoleacrylic acid | – | – | – | – | – | – |
| trans-ferulic acid | – | – | – | – | – | – |
| 4-methylcatechol | – | – | – | – | – | – |
| 4-methylcatechol | – | – | – | – | – | – |
| indoleacrylic acid | – | – | – | – | – | – |
| trans-ferulic acid | – | – | – | – | – | – |
| trans-ferulic acid | – | – | – | – | – | – |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | – | – | – |
| palmitoyl-Dl-carnitine chloride free | – | – | – | – | – | – |
| cortisone | V | – | – | – | – | – |
| testosterone | – | – | – | – | – | – |
| sodium glycodeoxycholate bioxtra | – | – | – | – | – | – |
| octadecanedioic acid | – | – | – | – | – | – |
| L-aspartyl-L-phenylalanine | – | – | – | – | – | – |
| indoleacrylic acid | – | – | – | – | – | – |
| dodecanoic acid | – | – | – | – | – | – |
| cuminaldehyde | – | – | – | – | – | – |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | – | – | – |
| cuminaldehyde | – | – | – | – | – | – |
| sodium glycodeoxycholate bioxtra | – | – | – | – | – | – |
| 4-methylcatechol | – | – | – | – | – | – |
| indoleacrylic acid | – | – | – | – | – | – |
| 4-methylcatechol | – | – | – | – | – | – |
| cuminaldehyde | – | – | – | – | – | – |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | – | – | – |
| L-aspartyl-L-phenylalanine | – | – | – | – | – | – |
| L-aspartyl-L-phenylalanine | – | – | – | – | – | – |
| L-aspartyl-L-phenylalanine | – | – | – | – | – | – |
| 4-8-dihydroxyquinoline-2-carboxylic | – | – | – | – | – | – |
| DL-glyceraldehyde | – | – | – | – | – | – |
| DL-glyceraldehyde | – | – | – | – | – | – |
| DL-glyceraldehyde | – | – | – | – | – | – |
| DL-glyceraldehyde | – | – | – | – | – | – |
| transtrans-farnesol | – | – | – | – | – | – |
| 2,3-dihydroxypropyl decanoate | – | – | – | – | – | – |
| 2,3-dihydroxypropyl decanoate | – | – | – | – | – | – |
| 2,3-dihydroxypropyl decanoate | – | – | – | – | – | – |
| transtrans-farnesol | – | – | – | – | – | – |
| octadecanamide | – | – | – | – | – | – |
| transtrans-farnesol | – | – | – | – | – | – |
| 2,3-dihydroxypropyl decanoate | – | – | – | – | – | – |
| 2-methoxycinnamic acid | – | – | – | – | – | – |
| octadecanamide | – | – | – | – | – | – |
| serotonin hydrochloride | – | – | – | – | – | – |
| transtrans-farnesol | – | – | – | – | – | – |
| 2-methoxycinnamic acid | – | – | – | – | – | – |
| retinoic acid | – | – | – | – | – | – |
| dehydroepiandrosterone | – | – | – | – | – | – |
| dehydroepiandrosterone | – | – | – | – | – | – |
| serotonin hydrochloride | – | – | – | – | – | – |
| homovanillic acid | – | – | – | – | – | – |
| serotonin hydrochloride | – | – | – | – | – | – |
| 2-methoxycinnamic acid | – | – | – | – | – | – |
| retinoic acid | – | – | – | – | – | – |
| 2-methoxycinnamic acid | – | – | – | – | – | – |
| octadecanamide | – | – | – | – | – | – |
| dehydroepiandrosterone | – | – | – | – | – | – |
| dehydroepiandrosterone | – | – | – | – | – | – |
| octadecanamide | – | – | – | – | – | – |
| 4-methoxyphenylacetic acid | V | – | – | – | – | – |
| homovanillic acid | – | – | – | – | – | – |
| retinoic acid | – | – | – | – | – | – |
| 3,4,5-trimethoxycinnamic acid | – | – | – | – | – | – |
| homovanillic acid | – | – | – | – | – | – |
| homovanillic acid | – | – | – | – | – | – |
| 4-methoxyphenylacetic acid | V | – | – | – | – | – |
| serotonin hydrochloride | – | – | – | – | – | – |
| 3,4,5-trimethoxycinnamic acid | – | – | – | – | – | – |
| 4-methoxyphenylacetic acid | V | – | – | – | – | – |
| 4-methoxyphenylacetic acid | V | – | – | – | – | – |
| retinoic acid | – | – | – | – | – | – |
| 1-palmitoyl-palmitoyl | – | – | – | – | – | – |
| 1-palmitoyl-palmitoyl | – | – | – | – | – | – |
| 3,4,5-trimethoxycinnamic acid | – | – | – | – | – | – |
| 1-palmitoyl-palmitoyl | – | – | – | – | – | – |
| 1-palmitoyl-palmitoyl | – | – | – | – | – | – |
| 3,4,5-trimethoxycinnamic acid | – | – | – | – | – | – |
Paper graphical summary
