Abstract
Genetic differences in individuals with regard to opioid-receptor signaling create clinical difficulties for opioid treatment; consequently, useful pharmacodynamic and predictive biomarkers are needed. In this prospective study, we studied gene expression changes in peripheral blood leukocytes using a microarray and real-time RT-PCR analysis to identify pharmacodynamic biomarkers for monitoring the effect of morphine in a cohort of opioid-treatment-naïve cancer patients. We also examined genetic variations in opioid receptor mu 1 (OPRM1, 118A→G) and catechol-O-methyltransferase (COMT, 472G→A) to evaluate predictive biomarkers of the treatment outcome of morphine. The plasma concentration of morphine was measured using a liquid chromatography-tandem mass spectrometry method. Microarray analysis revealed that the mRNA expression levels of arrestin β 1 (ARRB1) were significantly down-regulated by morphine treatment. Real-time RT-PCR analysis against independent samples confirmed the results (P=0.003) and changes during treatment were negatively correlated with the plasma morphine concentration (R=-0.42). No correlation was observed between the genotype of OPRM1 and morphine treatment; however, the plasma concentration of morphine and the required dose of morphine were significantly lower for the A/A genotype of COMT (vs. A/G+G/G, P=0.008 and 0.03). We found that changes in the expression of ARRB1 may be a novel pharmacodynamic biomarker and the COMT 472G→A genotype may be a predictive biomarker of the response to morphine treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 1393-1399 |
| Number of pages | 7 |
| Journal | Oncology Reports |
| Volume | 27 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2012 May |
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Keywords
- Arrestin
- Catechol-O-methyltransferase
- Microarray
- Morphine
- Opioid receptor μ 1
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Expression changes in arrestin β 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients. / Matsuoka, Hiromichi; Arao, Tokuzo; Makimura, Chihiro; Takeda, Masayuki; Kiyota, Hidemi; Tsurutani, Junji; Fujita, Yoshihiko; Matsumoto, Kazuko; Kimura, Hideharu; Otsuka, Masatomo; Koyama, Atsuko; Imamura, Chiyo; Tanigawara, Yusuke; Yamanaka, Takeharu; Tanaka, Kyoko; Nishio, Kazuto; Nakagawa, Kazuhiko.
In: Oncology Reports, Vol. 27, No. 5, 05.2012, p. 1393-1399.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Expression changes in arrestin β 1 and genetic variation in catechol-O-methyltransferase are biomarkers for the response to morphine treatment in cancer patients
AU - Matsuoka, Hiromichi
AU - Arao, Tokuzo
AU - Makimura, Chihiro
AU - Takeda, Masayuki
AU - Kiyota, Hidemi
AU - Tsurutani, Junji
AU - Fujita, Yoshihiko
AU - Matsumoto, Kazuko
AU - Kimura, Hideharu
AU - Otsuka, Masatomo
AU - Koyama, Atsuko
AU - Imamura, Chiyo
AU - Tanigawara, Yusuke
AU - Yamanaka, Takeharu
AU - Tanaka, Kyoko
AU - Nishio, Kazuto
AU - Nakagawa, Kazuhiko
PY - 2012/5
Y1 - 2012/5
N2 - Genetic differences in individuals with regard to opioid-receptor signaling create clinical difficulties for opioid treatment; consequently, useful pharmacodynamic and predictive biomarkers are needed. In this prospective study, we studied gene expression changes in peripheral blood leukocytes using a microarray and real-time RT-PCR analysis to identify pharmacodynamic biomarkers for monitoring the effect of morphine in a cohort of opioid-treatment-naïve cancer patients. We also examined genetic variations in opioid receptor mu 1 (OPRM1, 118A→G) and catechol-O-methyltransferase (COMT, 472G→A) to evaluate predictive biomarkers of the treatment outcome of morphine. The plasma concentration of morphine was measured using a liquid chromatography-tandem mass spectrometry method. Microarray analysis revealed that the mRNA expression levels of arrestin β 1 (ARRB1) were significantly down-regulated by morphine treatment. Real-time RT-PCR analysis against independent samples confirmed the results (P=0.003) and changes during treatment were negatively correlated with the plasma morphine concentration (R=-0.42). No correlation was observed between the genotype of OPRM1 and morphine treatment; however, the plasma concentration of morphine and the required dose of morphine were significantly lower for the A/A genotype of COMT (vs. A/G+G/G, P=0.008 and 0.03). We found that changes in the expression of ARRB1 may be a novel pharmacodynamic biomarker and the COMT 472G→A genotype may be a predictive biomarker of the response to morphine treatment.
AB - Genetic differences in individuals with regard to opioid-receptor signaling create clinical difficulties for opioid treatment; consequently, useful pharmacodynamic and predictive biomarkers are needed. In this prospective study, we studied gene expression changes in peripheral blood leukocytes using a microarray and real-time RT-PCR analysis to identify pharmacodynamic biomarkers for monitoring the effect of morphine in a cohort of opioid-treatment-naïve cancer patients. We also examined genetic variations in opioid receptor mu 1 (OPRM1, 118A→G) and catechol-O-methyltransferase (COMT, 472G→A) to evaluate predictive biomarkers of the treatment outcome of morphine. The plasma concentration of morphine was measured using a liquid chromatography-tandem mass spectrometry method. Microarray analysis revealed that the mRNA expression levels of arrestin β 1 (ARRB1) were significantly down-regulated by morphine treatment. Real-time RT-PCR analysis against independent samples confirmed the results (P=0.003) and changes during treatment were negatively correlated with the plasma morphine concentration (R=-0.42). No correlation was observed between the genotype of OPRM1 and morphine treatment; however, the plasma concentration of morphine and the required dose of morphine were significantly lower for the A/A genotype of COMT (vs. A/G+G/G, P=0.008 and 0.03). We found that changes in the expression of ARRB1 may be a novel pharmacodynamic biomarker and the COMT 472G→A genotype may be a predictive biomarker of the response to morphine treatment.
KW - Arrestin
KW - Catechol-O-methyltransferase
KW - Microarray
KW - Morphine
KW - Opioid receptor μ 1
UR - http://www.scopus.com/inward/record.url?scp=84863248608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863248608&partnerID=8YFLogxK
U2 - 10.3892/or.2012.1660
DO - 10.3892/or.2012.1660
M3 - Article
C2 - 22293824
AN - SCOPUS:84863248608
VL - 27
SP - 1393
EP - 1399
JO - Oncology Reports
JF - Oncology Reports
SN - 1021-335X
IS - 5
ER -