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High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-1

Purpose The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various ma...

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Published in:Journal of cancer research and clinical oncology 2020-01, Vol.146 (1), p.75-86
Main Authors: Maezawa, Yukio, Sakamaki, Kentaro, Oue, Naohide, Kimura, Yayoi, Hashimoto, Itaru, Hara, Kentaro, Kano, Kazuki, Aoyama, Toru, Hiroshima, Yukihiko, Yamada, Takanobu, Yamamoto, Naoto, Ogata, Takashi, Ito, Hiroyuki, Cho, Haruhiko, Shiozawa, Manabu, Yoshikawa, Takaki, Morinaga, Soichiro, Rino, Yasushi, Yasui, Wataru, Masuda, Munetaka, Miyagi, Yohei, Oshima, Takashi
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cited_by cdi_FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803
cites cdi_FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803
container_end_page 86
container_issue 1
container_start_page 75
container_title Journal of cancer research and clinical oncology
container_volume 146
creator Maezawa, Yukio
Sakamaki, Kentaro
Oue, Naohide
Kimura, Yayoi
Hashimoto, Itaru
Hara, Kentaro
Kano, Kazuki
Aoyama, Toru
Hiroshima, Yukihiko
Yamada, Takanobu
Yamamoto, Naoto
Ogata, Takashi
Ito, Hiroyuki
Cho, Haruhiko
Shiozawa, Manabu
Yoshikawa, Takaki
Morinaga, Soichiro
Rino, Yasushi
Yasui, Wataru
Masuda, Munetaka
Miyagi, Yohei
Oshima, Takashi
description Purpose The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/ low FPGS and low GGH /high FPGS . Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.
doi_str_mv 10.1007/s00432-019-03087-8
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High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/ low FPGS and low GGH /high FPGS . Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-019-03087-8</identifier><identifier>PMID: 31754833</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor - biosynthesis ; Biomarkers, Tumor - genetics ; Cancer Research ; Cell proliferation ; Chemotherapy ; Chemotherapy, Adjuvant ; DNA biosynthesis ; DNA repair ; Drug Combinations ; Female ; Folic acid ; gamma-Glutamyl Hydrolase - biosynthesis ; gamma-Glutamyl Hydrolase - genetics ; Gastric cancer ; Gastric Mucosa - enzymology ; Gene Expression ; Hematology ; Humans ; Hydrolase ; Internal Medicine ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Mucosa ; Multivariate analysis ; Neoplasm Staging ; Oncology ; Original Article – Cancer Research ; Original – Cancer Research ; Oxonic Acid - administration &amp; dosage ; Patients ; Peptide Synthases - biosynthesis ; Peptide Synthases - genetics ; Risk factors ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Stomach Neoplasms - drug therapy ; Stomach Neoplasms - enzymology ; Stomach Neoplasms - pathology ; Stomach Neoplasms - surgery ; Tegafur - administration &amp; dosage ; Thymidylate synthase</subject><ispartof>Journal of cancer research and clinical oncology, 2020-01, Vol.146 (1), p.75-86</ispartof><rights>The Author(s) 2019</rights><rights>Journal of Cancer Research and Clinical Oncology is a copyright of Springer, (2019). All Rights Reserved. © 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/ low FPGS and low GGH /high FPGS . Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. 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Public Health</subject><subject>Middle Aged</subject><subject>Mucosa</subject><subject>Multivariate analysis</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Original Article – Cancer Research</subject><subject>Original – Cancer Research</subject><subject>Oxonic Acid - administration &amp; dosage</subject><subject>Patients</subject><subject>Peptide Synthases - biosynthesis</subject><subject>Peptide Synthases - genetics</subject><subject>Risk factors</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Stomach Neoplasms - drug therapy</subject><subject>Stomach Neoplasms - enzymology</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - surgery</subject><subject>Tegafur - administration &amp; dosage</subject><subject>Thymidylate synthase</subject><issn>0171-5216</issn><issn>1432-1335</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9kstu1TAQhiMEoofCC7BAltiwCfiS6wYJVdAiVWIBrC0f20l8cOxgO-c078rDdEJKuSzIIsl4vvlnRv6z7DnBrwnG9ZuIccFojkmbY4abOm8eZDuyHhHGyofZDpOa5CUl1Vn2JMYDhris6ePsjMFP0TC2y35cmX5AvRhHkfd2TmJcLBoWFbwVUSPhFLL-hDpvFzvBa2NE0iguLg06rZS-mYKO0XiHRERT8L3zMRmJ9saPInzTISLj0CSS0S5FdDJpAFkprF2QUEfhpFYwREwBiuQaBnQaPDrpADOo0TgDOeiq0ATKftIQmOOaO8xQnpAc9OhhniCmZdP_nJOn2aNO2Kif3X3Ps68f3n-5uMqvP11-vHh3ncuiLlJe0K4smSq6tq33rZAtJbrq4GmaWglJKibaolKikpXStCF7VequYaXsOtyUDWbn2dtNd5r3o1YSlgzC8ikY2H7hXhj-d8aZgff-yKu2oJhQEHh1JxD891nHxEcTpbZWOO3nyOl6YS20qgB9-Q968HNwsB5QjNK6bVkBFN0oGXyMQXf3wxDMV_PwzTwczMN_moc3UPTizzXuS365BQC2ARFSrtfhd-__yN4C0AXZIg</recordid><startdate>20200101</startdate><enddate>20200101</enddate><creator>Maezawa, Yukio</creator><creator>Sakamaki, Kentaro</creator><creator>Oue, Naohide</creator><creator>Kimura, Yayoi</creator><creator>Hashimoto, Itaru</creator><creator>Hara, Kentaro</creator><creator>Kano, Kazuki</creator><creator>Aoyama, Toru</creator><creator>Hiroshima, Yukihiko</creator><creator>Yamada, Takanobu</creator><creator>Yamamoto, Naoto</creator><creator>Ogata, Takashi</creator><creator>Ito, Hiroyuki</creator><creator>Cho, Haruhiko</creator><creator>Shiozawa, Manabu</creator><creator>Yoshikawa, Takaki</creator><creator>Morinaga, Soichiro</creator><creator>Rino, Yasushi</creator><creator>Yasui, Wataru</creator><creator>Masuda, Munetaka</creator><creator>Miyagi, Yohei</creator><creator>Oshima, Takashi</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TO</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3349-2649</orcidid></search><sort><creationdate>20200101</creationdate><title>High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-1</title><author>Maezawa, Yukio ; Sakamaki, Kentaro ; Oue, Naohide ; Kimura, Yayoi ; Hashimoto, Itaru ; Hara, Kentaro ; Kano, Kazuki ; Aoyama, Toru ; Hiroshima, Yukihiko ; Yamada, Takanobu ; Yamamoto, Naoto ; Ogata, Takashi ; Ito, Hiroyuki ; Cho, Haruhiko ; Shiozawa, Manabu ; Yoshikawa, Takaki ; Morinaga, Soichiro ; Rino, Yasushi ; Yasui, Wataru ; Masuda, Munetaka ; Miyagi, Yohei ; Oshima, Takashi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biomarkers, Tumor - biosynthesis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Cancer Research</topic><topic>Cell proliferation</topic><topic>Chemotherapy</topic><topic>Chemotherapy, Adjuvant</topic><topic>DNA biosynthesis</topic><topic>DNA repair</topic><topic>Drug Combinations</topic><topic>Female</topic><topic>Folic acid</topic><topic>gamma-Glutamyl Hydrolase - biosynthesis</topic><topic>gamma-Glutamyl Hydrolase - genetics</topic><topic>Gastric cancer</topic><topic>Gastric Mucosa - enzymology</topic><topic>Gene Expression</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hydrolase</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine &amp; 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High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1. Methods Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection. Results While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29–5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/ low FPGS and low GGH /high FPGS . Patients without adjuvant treatment showed no significant difference. Conclusion GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>31754833</pmid><doi>10.1007/s00432-019-03087-8</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0003-3349-2649</orcidid><oa>free_for_read</oa></addata></record>
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identifier ISSN: 0171-5216
ispartof Journal of cancer research and clinical oncology, 2020-01, Vol.146 (1), p.75-86
issn 0171-5216
1432-1335
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6942012
source Springer Nature
subjects Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biomarkers, Tumor - biosynthesis
Biomarkers, Tumor - genetics
Cancer Research
Cell proliferation
Chemotherapy
Chemotherapy, Adjuvant
DNA biosynthesis
DNA repair
Drug Combinations
Female
Folic acid
gamma-Glutamyl Hydrolase - biosynthesis
gamma-Glutamyl Hydrolase - genetics
Gastric cancer
Gastric Mucosa - enzymology
Gene Expression
Hematology
Humans
Hydrolase
Internal Medicine
Male
Medicine
Medicine & Public Health
Middle Aged
Mucosa
Multivariate analysis
Neoplasm Staging
Oncology
Original Article – Cancer Research
Original – Cancer Research
Oxonic Acid - administration & dosage
Patients
Peptide Synthases - biosynthesis
Peptide Synthases - genetics
Risk factors
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Stomach Neoplasms - drug therapy
Stomach Neoplasms - enzymology
Stomach Neoplasms - pathology
Stomach Neoplasms - surgery
Tegafur - administration & dosage
Thymidylate synthase
title High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-1
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