Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer
Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer. Among 322 patients enrolled, 65/82 patients were determined as GGT pos...
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| creator | Wang, Qinchuan Shu, Xiang Dong, Yong Zhou, Jichun Teng, Rongyue Shen, Jianguo Chen, Yongxia Dong, Mingjun Zhang, Wenjun Huang, Yasheng Xie, Shuduo Wei, Qun Zhao, Wenhe Chen, Wenjun Yuan, Xiaoming Qi, Xu Wang, Linbo |
| description | Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer.
Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival (P log-rank=0.001) and progress-free survival (P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways.
Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms.
Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up. |
| doi_str_mv | 10.18632/oncotarget.15609 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5482647</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>28404903</sourcerecordid><originalsourceid>FETCH-LOGICAL-c422t-aa662815181097b2e6d5b9cfbc327179494bbcc59c3c9c13c92eebc96263c76c3</originalsourceid><addsrcrecordid>eNpVkU1PxCAQhonRqFn3B3gx_AC7FtrScjExxq_ExMt6buh0tqItNEA13vzp4q4fKweYZOZ5h5mXkGOWLlglMn5mDdigXIdhwQqRyh1yyGQuE14U2e5WfEDm3j-n8RR5WXG5Tw54lae5TLND8rGcBuuoMi316KaBdmoYVNL1U1DDe0-DU8aPOAbdKo-n1OAbHZ3tjPVBw5obbI8w9cpRbQK60WFQQVtD7Srmqe1b2mg7KPeCXyWxgw8usqAMoDsieyvVe5x_vzPyeH21vLxN7h9u7i4v7hPIOQ-JUkLwihWsYqksG46iLRoJqwYyXrIyzpo3DUAhIQMJLF4csQEpuMigFJDNyPlGd5yaAVtAE0fr69Hp-LP32ipd_88Y_VR39rUu8oqLvIwCbCMAznrvcPXLsrReO1L_OVKvHYnMyXbTX-Jn_9knGQOO4w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free E- Journals</source><source>PubMed Central Open Access</source><creator>Wang, Qinchuan ; Shu, Xiang ; Dong, Yong ; Zhou, Jichun ; Teng, Rongyue ; Shen, Jianguo ; Chen, Yongxia ; Dong, Mingjun ; Zhang, Wenjun ; Huang, Yasheng ; Xie, Shuduo ; Wei, Qun ; Zhao, Wenhe ; Chen, Wenjun ; Yuan, Xiaoming ; Qi, Xu ; Wang, Linbo</creator><creatorcontrib>Wang, Qinchuan ; Shu, Xiang ; Dong, Yong ; Zhou, Jichun ; Teng, Rongyue ; Shen, Jianguo ; Chen, Yongxia ; Dong, Mingjun ; Zhang, Wenjun ; Huang, Yasheng ; Xie, Shuduo ; Wei, Qun ; Zhao, Wenhe ; Chen, Wenjun ; Yuan, Xiaoming ; Qi, Xu ; Wang, Linbo</creatorcontrib><description>Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer.
Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival (P log-rank=0.001) and progress-free survival (P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways.
Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms.
Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.15609</identifier><identifier>PMID: 28404903</identifier><language>eng</language><publisher>United States: Impact Journals LLC</publisher><subject>Biomarkers, Tumor - metabolism ; Carcinogenesis ; Female ; gamma-Glutamyltransferase - genetics ; gamma-Glutamyltransferase - metabolism ; Glutathione - metabolism ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - metabolism ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - metabolism ; Research Paper ; Retrospective Studies ; Stomach Neoplasms - diagnosis ; Stomach Neoplasms - genetics ; Stomach Neoplasms - mortality ; Survival Analysis</subject><ispartof>Oncotarget, 2017-05, Vol.8 (22), p.36171-36184</ispartof><rights>Copyright: © 2017 Wang et al. 2017</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c422t-aa662815181097b2e6d5b9cfbc327179494bbcc59c3c9c13c92eebc96263c76c3</citedby><cites>FETCH-LOGICAL-c422t-aa662815181097b2e6d5b9cfbc327179494bbcc59c3c9c13c92eebc96263c76c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482647/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5482647/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28404903$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Qinchuan</creatorcontrib><creatorcontrib>Shu, Xiang</creatorcontrib><creatorcontrib>Dong, Yong</creatorcontrib><creatorcontrib>Zhou, Jichun</creatorcontrib><creatorcontrib>Teng, Rongyue</creatorcontrib><creatorcontrib>Shen, Jianguo</creatorcontrib><creatorcontrib>Chen, Yongxia</creatorcontrib><creatorcontrib>Dong, Mingjun</creatorcontrib><creatorcontrib>Zhang, Wenjun</creatorcontrib><creatorcontrib>Huang, Yasheng</creatorcontrib><creatorcontrib>Xie, Shuduo</creatorcontrib><creatorcontrib>Wei, Qun</creatorcontrib><creatorcontrib>Zhao, Wenhe</creatorcontrib><creatorcontrib>Chen, Wenjun</creatorcontrib><creatorcontrib>Yuan, Xiaoming</creatorcontrib><creatorcontrib>Qi, Xu</creatorcontrib><creatorcontrib>Wang, Linbo</creatorcontrib><title>Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer.
Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival (P log-rank=0.001) and progress-free survival (P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways.
Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms.
Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up.</description><subject>Biomarkers, Tumor - metabolism</subject><subject>Carcinogenesis</subject><subject>Female</subject><subject>gamma-Glutamyltransferase - genetics</subject><subject>gamma-Glutamyltransferase - metabolism</subject><subject>Glutathione - metabolism</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prognosis</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>Proto-Oncogene Proteins p21(ras) - metabolism</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, ErbB-2 - metabolism</subject><subject>Research Paper</subject><subject>Retrospective Studies</subject><subject>Stomach Neoplasms - diagnosis</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - mortality</subject><subject>Survival Analysis</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkU1PxCAQhonRqFn3B3gx_AC7FtrScjExxq_ExMt6buh0tqItNEA13vzp4q4fKweYZOZ5h5mXkGOWLlglMn5mDdigXIdhwQqRyh1yyGQuE14U2e5WfEDm3j-n8RR5WXG5Tw54lae5TLND8rGcBuuoMi316KaBdmoYVNL1U1DDe0-DU8aPOAbdKo-n1OAbHZ3tjPVBw5obbI8w9cpRbQK60WFQQVtD7Srmqe1b2mg7KPeCXyWxgw8usqAMoDsieyvVe5x_vzPyeH21vLxN7h9u7i4v7hPIOQ-JUkLwihWsYqksG46iLRoJqwYyXrIyzpo3DUAhIQMJLF4csQEpuMigFJDNyPlGd5yaAVtAE0fr69Hp-LP32ipd_88Y_VR39rUu8oqLvIwCbCMAznrvcPXLsrReO1L_OVKvHYnMyXbTX-Jn_9knGQOO4w</recordid><startdate>20170530</startdate><enddate>20170530</enddate><creator>Wang, Qinchuan</creator><creator>Shu, Xiang</creator><creator>Dong, Yong</creator><creator>Zhou, Jichun</creator><creator>Teng, Rongyue</creator><creator>Shen, Jianguo</creator><creator>Chen, Yongxia</creator><creator>Dong, Mingjun</creator><creator>Zhang, Wenjun</creator><creator>Huang, Yasheng</creator><creator>Xie, Shuduo</creator><creator>Wei, Qun</creator><creator>Zhao, Wenhe</creator><creator>Chen, Wenjun</creator><creator>Yuan, Xiaoming</creator><creator>Qi, Xu</creator><creator>Wang, Linbo</creator><general>Impact Journals LLC</general><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>5PM</scope></search><sort><creationdate>20170530</creationdate><title>Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer</title><author>Wang, Qinchuan ; Shu, Xiang ; Dong, Yong ; Zhou, Jichun ; Teng, Rongyue ; Shen, Jianguo ; Chen, Yongxia ; Dong, Mingjun ; Zhang, Wenjun ; Huang, Yasheng ; Xie, Shuduo ; Wei, Qun ; Zhao, Wenhe ; Chen, Wenjun ; Yuan, Xiaoming ; Qi, Xu ; Wang, Linbo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-aa662815181097b2e6d5b9cfbc327179494bbcc59c3c9c13c92eebc96263c76c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Biomarkers, Tumor - metabolism</topic><topic>Carcinogenesis</topic><topic>Female</topic><topic>gamma-Glutamyltransferase - genetics</topic><topic>gamma-Glutamyltransferase - metabolism</topic><topic>Glutathione - metabolism</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>Proto-Oncogene Proteins p21(ras) - metabolism</topic><topic>Receptor, ErbB-2 - genetics</topic><topic>Receptor, ErbB-2 - metabolism</topic><topic>Research Paper</topic><topic>Retrospective Studies</topic><topic>Stomach Neoplasms - diagnosis</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - mortality</topic><topic>Survival Analysis</topic><toplevel>online_resources</toplevel><creatorcontrib>Wang, Qinchuan</creatorcontrib><creatorcontrib>Shu, Xiang</creatorcontrib><creatorcontrib>Dong, Yong</creatorcontrib><creatorcontrib>Zhou, Jichun</creatorcontrib><creatorcontrib>Teng, Rongyue</creatorcontrib><creatorcontrib>Shen, Jianguo</creatorcontrib><creatorcontrib>Chen, Yongxia</creatorcontrib><creatorcontrib>Dong, Mingjun</creatorcontrib><creatorcontrib>Zhang, Wenjun</creatorcontrib><creatorcontrib>Huang, Yasheng</creatorcontrib><creatorcontrib>Xie, Shuduo</creatorcontrib><creatorcontrib>Wei, Qun</creatorcontrib><creatorcontrib>Zhao, Wenhe</creatorcontrib><creatorcontrib>Chen, Wenjun</creatorcontrib><creatorcontrib>Yuan, Xiaoming</creatorcontrib><creatorcontrib>Qi, Xu</creatorcontrib><creatorcontrib>Wang, Linbo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Qinchuan</au><au>Shu, Xiang</au><au>Dong, Yong</au><au>Zhou, Jichun</au><au>Teng, Rongyue</au><au>Shen, Jianguo</au><au>Chen, Yongxia</au><au>Dong, Mingjun</au><au>Zhang, Wenjun</au><au>Huang, Yasheng</au><au>Xie, Shuduo</au><au>Wei, Qun</au><au>Zhao, Wenhe</au><au>Chen, Wenjun</au><au>Yuan, Xiaoming</au><au>Qi, Xu</au><au>Wang, Linbo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2017-05-30</date><risdate>2017</risdate><volume>8</volume><issue>22</issue><spage>36171</spage><epage>36184</epage><pages>36171-36184</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Gastric Cancer is one of the most lethal malignancies worldwide. Gamma-glutamyl transpeptidase (GGT) is an enzyme mainly involved in cellular glutathione homeostasis. We aim to explore the clinical value of GGT in gastric cancer.
Among 322 patients enrolled, 65/82 patients were determined as GGT positive in serum/tumor, respectively. High tumor GGT expression is significantly associated with lymph node metastasis, histological subtype, and Her2 expression. Kaplan-Meier curve shows that high tumor GGT patients have shorter overall survival (P log-rank=0.001) and progress-free survival (P log-rank =0.001). Patients with both high tumor and serum GGT have the poorest prognosis. The multivariable Cox analysis shows that the hazard ratio of overall survival for high tumor GGT is 1.69 (95% CI 1.19-2.37). High serum GGT is a poor prognostic factor in adjuvant chemotherapy hazard ratio=2.18, 95%CI (1.15-4.47). These findings were further validated in six online datasets. Gene Sets Enrichment Analysis showed that GGT promotes cancer progression through EMT, KRAS, SRC and PKCA pathways.
Tumor GGT and serum GGT levels were evaluated with immuno-histochemistry staining and enzymatic assay, respectively. Kaplan-Meier curve and Cox regression model were used to test the association between GGT and gastric cancer prognosis. Independent datasets from Gene Expression Omnibus and Gene Sets Enrichment Analysis were applied to validate the findings and explore the potential mechanisms.
Both tumor GGT and serum GGT are poor prognostic factors in gastric cancer. Patients with high tumor and serum GGT levels require more intense treatment and follow-up.</abstract><cop>United States</cop><pub>Impact Journals LLC</pub><pmid>28404903</pmid><doi>10.18632/oncotarget.15609</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biomarkers, Tumor - metabolism Carcinogenesis Female gamma-Glutamyltransferase - genetics gamma-Glutamyltransferase - metabolism Glutathione - metabolism Humans Lymphatic Metastasis Male Middle Aged Prognosis Proto-Oncogene Proteins p21(ras) - genetics Proto-Oncogene Proteins p21(ras) - metabolism Receptor, ErbB-2 - genetics Receptor, ErbB-2 - metabolism Research Paper Retrospective Studies Stomach Neoplasms - diagnosis Stomach Neoplasms - genetics Stomach Neoplasms - mortality Survival Analysis |
| title | Tumor and serum gamma-glutamyl transpeptidase, new prognostic and molecular interpretation of an old biomarker in gastric cancer |
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