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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 |
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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 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6942012</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2317595806</sourcerecordid><originalsourceid>FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803</originalsourceid><addsrcrecordid>eNp9kstu1TAQhiMEoofCC7BAltiwCfiS6wYJVdAiVWIBrC0f20l8cOxgO-c078rDdEJKuSzIIsl4vvlnRv6z7DnBrwnG9ZuIccFojkmbY4abOm8eZDuyHhHGyofZDpOa5CUl1Vn2JMYDhris6ePsjMFP0TC2y35cmX5AvRhHkfd2TmJcLBoWFbwVUSPhFLL-hDpvFzvBa2NE0iguLg06rZS-mYKO0XiHRERT8L3zMRmJ9saPInzTISLj0CSS0S5FdDJpAFkprF2QUEfhpFYwREwBiuQaBnQaPDrpADOo0TgDOeiq0ATKftIQmOOaO8xQnpAc9OhhniCmZdP_nJOn2aNO2Kif3X3Ps68f3n-5uMqvP11-vHh3ncuiLlJe0K4smSq6tq33rZAtJbrq4GmaWglJKibaolKikpXStCF7VequYaXsOtyUDWbn2dtNd5r3o1YSlgzC8ikY2H7hXhj-d8aZgff-yKu2oJhQEHh1JxD891nHxEcTpbZWOO3nyOl6YS20qgB9-Q968HNwsB5QjNK6bVkBFN0oGXyMQXf3wxDMV_PwzTwczMN_moc3UPTizzXuS365BQC2ARFSrtfhd-__yN4C0AXZIg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2332279934</pqid></control><display><type>article</type><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><source>Springer Nature</source><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</creator><creatorcontrib>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</creatorcontrib><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.</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 & 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</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”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803</citedby><cites>FETCH-LOGICAL-c474t-42f553d4f997b9ac921e6ffff887dac163a946da6c6de281bd5ef835cff085803</cites><orcidid>0000-0003-3349-2649</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31754833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Maezawa, Yukio</creatorcontrib><creatorcontrib>Sakamaki, Kentaro</creatorcontrib><creatorcontrib>Oue, Naohide</creatorcontrib><creatorcontrib>Kimura, Yayoi</creatorcontrib><creatorcontrib>Hashimoto, Itaru</creatorcontrib><creatorcontrib>Hara, Kentaro</creatorcontrib><creatorcontrib>Kano, Kazuki</creatorcontrib><creatorcontrib>Aoyama, Toru</creatorcontrib><creatorcontrib>Hiroshima, Yukihiko</creatorcontrib><creatorcontrib>Yamada, Takanobu</creatorcontrib><creatorcontrib>Yamamoto, Naoto</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Ito, Hiroyuki</creatorcontrib><creatorcontrib>Cho, Haruhiko</creatorcontrib><creatorcontrib>Shiozawa, Manabu</creatorcontrib><creatorcontrib>Yoshikawa, Takaki</creatorcontrib><creatorcontrib>Morinaga, Soichiro</creatorcontrib><creatorcontrib>Rino, Yasushi</creatorcontrib><creatorcontrib>Yasui, Wataru</creatorcontrib><creatorcontrib>Masuda, Munetaka</creatorcontrib><creatorcontrib>Miyagi, Yohei</creatorcontrib><creatorcontrib>Oshima, Takashi</creatorcontrib><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><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><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.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor - biosynthesis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Cancer Research</subject><subject>Cell proliferation</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Adjuvant</subject><subject>DNA biosynthesis</subject><subject>DNA repair</subject><subject>Drug Combinations</subject><subject>Female</subject><subject>Folic acid</subject><subject>gamma-Glutamyl Hydrolase - biosynthesis</subject><subject>gamma-Glutamyl Hydrolase - genetics</subject><subject>Gastric cancer</subject><subject>Gastric Mucosa - enzymology</subject><subject>Gene Expression</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hydrolase</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & 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 & 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 & 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 & Public Health</topic><topic>Middle Aged</topic><topic>Mucosa</topic><topic>Multivariate analysis</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Original Article – Cancer Research</topic><topic>Original – Cancer Research</topic><topic>Oxonic Acid - administration & dosage</topic><topic>Patients</topic><topic>Peptide Synthases - biosynthesis</topic><topic>Peptide Synthases - genetics</topic><topic>Risk factors</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Stomach Neoplasms - drug therapy</topic><topic>Stomach Neoplasms - enzymology</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach Neoplasms - surgery</topic><topic>Tegafur - administration & dosage</topic><topic>Thymidylate synthase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Maezawa, Yukio</creatorcontrib><creatorcontrib>Sakamaki, Kentaro</creatorcontrib><creatorcontrib>Oue, Naohide</creatorcontrib><creatorcontrib>Kimura, Yayoi</creatorcontrib><creatorcontrib>Hashimoto, Itaru</creatorcontrib><creatorcontrib>Hara, Kentaro</creatorcontrib><creatorcontrib>Kano, Kazuki</creatorcontrib><creatorcontrib>Aoyama, Toru</creatorcontrib><creatorcontrib>Hiroshima, Yukihiko</creatorcontrib><creatorcontrib>Yamada, Takanobu</creatorcontrib><creatorcontrib>Yamamoto, Naoto</creatorcontrib><creatorcontrib>Ogata, Takashi</creatorcontrib><creatorcontrib>Ito, Hiroyuki</creatorcontrib><creatorcontrib>Cho, Haruhiko</creatorcontrib><creatorcontrib>Shiozawa, Manabu</creatorcontrib><creatorcontrib>Yoshikawa, Takaki</creatorcontrib><creatorcontrib>Morinaga, Soichiro</creatorcontrib><creatorcontrib>Rino, Yasushi</creatorcontrib><creatorcontrib>Yasui, Wataru</creatorcontrib><creatorcontrib>Masuda, Munetaka</creatorcontrib><creatorcontrib>Miyagi, Yohei</creatorcontrib><creatorcontrib>Oshima, Takashi</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cancer research and clinical oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Maezawa, Yukio</au><au>Sakamaki, Kentaro</au><au>Oue, Naohide</au><au>Kimura, Yayoi</au><au>Hashimoto, Itaru</au><au>Hara, Kentaro</au><au>Kano, Kazuki</au><au>Aoyama, Toru</au><au>Hiroshima, Yukihiko</au><au>Yamada, Takanobu</au><au>Yamamoto, Naoto</au><au>Ogata, Takashi</au><au>Ito, Hiroyuki</au><au>Cho, Haruhiko</au><au>Shiozawa, Manabu</au><au>Yoshikawa, Takaki</au><au>Morinaga, Soichiro</au><au>Rino, Yasushi</au><au>Yasui, Wataru</au><au>Masuda, Munetaka</au><au>Miyagi, Yohei</au><au>Oshima, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Journal of cancer research and clinical oncology</jtitle><stitle>J Cancer Res Clin Oncol</stitle><addtitle>J Cancer Res Clin Oncol</addtitle><date>2020-01-01</date><risdate>2020</risdate><volume>146</volume><issue>1</issue><spage>75</spage><epage>86</epage><pages>75-86</pages><issn>0171-5216</issn><eissn>1432-1335</eissn><abstract>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.</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> |
fulltext | fulltext |
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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