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JKM > Volume 38(1); 2017 > Article
Park, Sung, Lee, and Yoo: Correlation Analysis of Organic Acid Comprehensive Profile Markers with Chemotherapy Induced Peripheral Neuropathy in Cancer Patients

Abstract

Objectives

The purpose of this study is to evaluate the urinary organic acid comprehensive profile for chemotherapy induced peripheral neuropathy (CIPN).

Methods

Participants are 66 patients with CIPN who had symptom (Visual analog scale ≥ 30 mm, Eastern Cooperative Oncology Group ≤ 2). Participants were tested with organic acid comprehensive profile markers.

Results

Positive Correlation was observed in the neurotransmitter metabolism markers, N-methyl-D-aspartate (NMDA) modulators markers, detoxification markers, energy production markers, amino acid metabolism markers, and intestinal dysbiosis markers. Especially, all the neurotransmitter metabolism markers were showed positive rate of 44%. In addition, neuro-endo-immune was associated with energy metabolism (mitochondrial dysfunction) in CIPN of cancer patient. especially detoxification, intestinal bacterial hyperplasia, vitamin deficiency (folate, complex B group, vitamin C).

Conclusions

Significant urinary organic acid comprehensive profile results were obtained in cancer patients who induced peripheral neuropathy by chemotherapy.

Table 1
Organic Acid Comprehensive Profile Markers Associated with Chemotherapy Induced Peripheral Neuropathy
Cause of Neuropathy Markers
Energy production markers 3-Hydroxy-3-methylglutarate (HMG), a-Ketoglutarate(AKG), CIS-Aconitate, Citrate, Fumerate, Isocitrate, Malate, Succinate
Vitamin B-Complex markers a-Ketoisocaproate, a-Ketoisovalerate, a-Keto-β-methylvalerate, Methylcitric Acid, β-Hydroxyisovalerate, Xanthurenate, Ascorbate
Neurotransmitter Metabolism markers 5-Hydroxyindoleacetate (5-HIA), Homovanillate (HVA), Vanilmandelate (VMA)
Methylation cofactor markers Formiminoglutamate(FIGLU), Methylmalonate
NMDA Modulators markers Kynurenate, Picolinate, Quinolinate
Oxidative Damage and Antioxidant markers 8-Hydroxy-2-deoxyguanosine(8-OHdG), p-Hydroxyphenyllactate (HPLA)
Detoxification Indicators markers 2-Hydroxyhippuric Acid, 2-Methylhippurate, 2-Oxoglutaric Acid, a-Hydroxybutyrate (AHB), Glucarate (glucuronic acid), Orotate, Phthalate, Pyroglutamate, 4-Cresol
Ketone Body Metabolism markers Acetoacetic Acid, β-Hydroxybutyrate
Amino Acid Metabolism markers 2-Hydroxyisocaproic acid, 2-Hydroxyisovaleric acid, 3-Hydroxyglutaric acid, 3-Methylglutaric acid, 3-Methylglutaric acid, Homogentisic Acid, Mandelic Acid, Phenylpyruvic Acid
Intestinal dysbiosis markers 2-Hydroxyphenylacetate, 3,4-Dihydroxyphenylpropionate (DHPPA), 4-Cresol, 4-Hydroxyhippurate, 5-Hydroxy-methyl-furoate, Benzoate, Citramalic Acid, Furan-2,5-dicarboxylate, Furancarbonylglycine, Hippurate, Indoleacetate, Oxalate, Phenylacetate (PAA), Phenylpropionate (PPA), p-Hydroxybenzoate, p-Hydroxyphenylacetate, Tartarate, Tricarballylate, 4-Hydroxyphenylacetate, D-Lactate.
Table 2
General Characteristics of Subjects
n=66 n=66
Sex (n, %) VAS (M±SD)
 Male 2 (3.0%)  Hand 48.86 ± 13.89
 Female 64 (97.0%)  Feet 50.40 ± 16.56

Age (years/M±SD) 49.03 ± 7.85 ECOG (M±SD) 1.09 ± 0.29

Weight (kg/M±SD) 58.38 ± 8.16

Height (cm/M±SD) 158.80 ± 5.77  Moving impediment, Visit1 (M±SD) 2.63 ± 0.67

Vital sign, Visit 1 (M±SD)  Painful impediment, Visit1 (M±SD) 2.60 ± 0.63
 Systolic BP, mmHg 112.57 ± 17.39 Fixed impediment, Visit1 (M±SD) 2.73 ± 0.61
 Diastolic BP, mmHg 72.50 ± 11.23 Deficiency impediment, Visit1 (M±SD) 3.26 ± 0.55
 Heart(pulse) rate 77.27 ± 11.89
 Body temperature 36.66 ± 0.21

Vital sign, Visit 2 (M±SD)
 Systolic BP, mmHg 109.58 ± 14.09 Moving impediment, Visit2 (M±SD) 2.48 ± 0.70
 Diastolic BP, mmHg 72.11 ± 8.82 Painful impediment, Visit2 (M±SD) 2.52 ± 0.57
 Heart(pulse) rate 75.29 ± 9.08 Fixed impediment, Visit2 (M±SD) 2.57 ± 0.55
 Body temperature 36.56 ± 0.21 Deficiency impediment, Visit2 (M±SD) 3.18 ± 0.59

Smoking (n, %)
 Yes
 No 66 (100.0%)

Alcohol (n, %) FACT-G Total (M±SD) 46.52 ± 7.77
 Yes 1 (1.5%)  PWB (M±SD) 17.48 ± 5.04
 No 65 (98.5%)  SWB (M±SD) 11.35 ± 4.81

CIPN (n, %)  EWB (M±SD) 5.36 ± 4.86
 Yes 66 (100.0%)  FWB (M±SD) 12.32 ± 4.79
 No

CIPN (Hand) (n, %) CIPN-20 Total 39.03 ± 8.26
 Yes 65 (98.5%)
 No 1 (1.5%)

CIPN (Feet) (n, %)
 Yes 64 (97.0%)
 No 2 (3.0%)

Past History (n, %)
 Yes 66 (100.0%)
 No

Taking a medication History (n, %)
 Yes 48 (72.7%)
 No 18 (27.3%)

Adverse Reactions (n, %)
 Yes 5 (7.6%)
 No 61 (92.4%)

Changes in concomitant medications (n, %)
 Yes 6 (9.1%)
 No 60 (90.9%)

CIPN: Chemotherapy Induced Peripheral Neuropathy; VAS: Visual Analog Scale; ECOG: Eastern Cooperative Oncology Group; FACT-G: Functional Assessment of Cancer Therapy-General

Table 3
The Ranking of Cases in Organic Acid Comprehensive Profile
Ranking Markers Reference Range (mmol/mol creatinine) Positive Rate

Abnormal Cases Rate Mean ± Standard Deviation
1 Hippurate 0.00–314.32 25 38% 694.12±444.99
2 Phenylpyruvate 0.00–0.06 20 30% 1.47±6.25
3 5-Hydroxyindoleacetate 0.00–5.31 16 24% 7.86±3.50
3 2-Hydroxyhippurate 0.00–0.91 16 24% 41.43±76.88
5 Citrate 9.82–210.55 15 23% 280.36±73.51
5 Vanilmandelate 0.11–0.82 15 23% 1.03±0.40
7 Homovanillate 0.00–2.07 13 20% 2.45±0.45
7 α-Hydroxybutyrate 0.00–0.42 13 20% 0.63±0.46
9 Tricarballylate 0.00–0.13 12 18% 0.19±0.05
10 Quinolinate 0.25–1.71 11 17% 2.13±0.38

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