Correlation Analysis of Organic Acid Comprehensive Profile Markers with Chemotherapy Induced Peripheral Neuropathy in Cancer Patients

Ji Hye Park; Simon SangYup Sung; Jin Sun Lee; Hwa Seung Yoo; Park, Ji Hye; Sung, Simon SangYup; Lee, Jin Sun; Yoo, Hwa Seung

doi:10.13048/jkm.17007

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

Original Article

The Journal of Korean Medicine 2017; 38(1): 72-80.

Published online: March 31, 2017

DOI: https://doi.org/10.13048/jkm.17007

Correlation Analysis of Organic Acid Comprehensive Profile Markers with Chemotherapy Induced Peripheral Neuropathy in Cancer Patients

Ji Hye Park¹, Simon SangYup Sung²^{, 3}, Jin Sun Lee⁴^{, *}, Hwa Seung Yoo¹^{, *}

¹East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University

²SUNIN BIO, Chungnam National University Hospital

³Seoul Clinical Laboratories, Chungnam National University Hospital

⁴Department of surgery, Chungnam National University Hospital

Correspondence to：박영배(Young-Bae Park) 경희대학교 한의과대학 진단·생기능의학 교실 Tel：+82-2-958-9242, Fax：+82-2-958-9104, E-mail: altyhs@dju.kr, 대전광역시 중구 문화로 282 충남대학교병원, Tel: +82-42-280-8503, Fax: +82-42-257-8024, E-mail: leejin123@hanmail.net

Received February 28, 2017 Revised March 20, 2017 Accepted March 24, 2017

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.

Keywords: Chemotherapy induced peripheral neuropathy, Urinary organic acid, Neurotransmitter metabolism, Bio markers

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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