Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma
Background Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC afte...
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Veröffentlicht in: | Journal of gastroenterology 2020-12, Vol.55 (12), p.1171-1182 |
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creator | Yu, Wen-Long Yu, Guanzhen Dong, Hui Chen, Ke Xie, Jun Yu, Hua Ji, Yuan Yang, Guang-Shun Li, Ai-Jun Cong, Wen-Ming Jin, Guang-Zhi |
description | Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
|
doi_str_mv | 10.1007/s00535-020-01729-0 |
format | Article |
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Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
< 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4–31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6–18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro.
Conclusions
Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.</description><identifier>ISSN: 0944-1174</identifier><identifier>EISSN: 1435-5922</identifier><identifier>DOI: 10.1007/s00535-020-01729-0</identifier><identifier>PMID: 33089343</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Abdominal Surgery ; Biliary Tract ; Bioinformatics ; Cell migration ; Cholangiocarcinoma ; Colorectal Surgery ; Gastroenterology ; Hepatology ; Immunohistochemistry ; Liver cancer ; Medicine ; Medicine & Public Health ; Nomograms ; Original Article—Liver ; Pancreas ; Prediction models ; Proteomics ; Risk groups ; Surgery ; Surgical Oncology ; Tumor markers</subject><ispartof>Journal of gastroenterology, 2020-12, Vol.55 (12), p.1171-1182</ispartof><rights>Japanese Society of Gastroenterology 2020</rights><rights>Japanese Society of Gastroenterology 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-563206d4416b657392f191a7e2104ec78f8611e840c7c9735c907548d543ca193</citedby><cites>FETCH-LOGICAL-c465t-563206d4416b657392f191a7e2104ec78f8611e840c7c9735c907548d543ca193</cites><orcidid>0000-0001-8961-4196</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s00535-020-01729-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s00535-020-01729-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27923,27924,41487,42556,51318</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33089343$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yu, Wen-Long</creatorcontrib><creatorcontrib>Yu, Guanzhen</creatorcontrib><creatorcontrib>Dong, Hui</creatorcontrib><creatorcontrib>Chen, Ke</creatorcontrib><creatorcontrib>Xie, Jun</creatorcontrib><creatorcontrib>Yu, Hua</creatorcontrib><creatorcontrib>Ji, Yuan</creatorcontrib><creatorcontrib>Yang, Guang-Shun</creatorcontrib><creatorcontrib>Li, Ai-Jun</creatorcontrib><creatorcontrib>Cong, Wen-Ming</creatorcontrib><creatorcontrib>Jin, Guang-Zhi</creatorcontrib><title>Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma</title><title>Journal of gastroenterology</title><addtitle>J Gastroenterol</addtitle><addtitle>J Gastroenterol</addtitle><description>Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
< 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4–31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6–18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro.
Conclusions
Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.</description><subject>Abdominal Surgery</subject><subject>Biliary Tract</subject><subject>Bioinformatics</subject><subject>Cell migration</subject><subject>Cholangiocarcinoma</subject><subject>Colorectal Surgery</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Immunohistochemistry</subject><subject>Liver cancer</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Nomograms</subject><subject>Original Article—Liver</subject><subject>Pancreas</subject><subject>Prediction models</subject><subject>Proteomics</subject><subject>Risk groups</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Tumor markers</subject><issn>0944-1174</issn><issn>1435-5922</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp9kctOHDEQRS2UKAxDfiALZCkbNh3Kr3Z7iVBIkJBgAWvL464eTHrswe6OxN_Hk-EhZZGVJde511YdQr4w-MYA9FkBUEI1wKEBprlp4IAsmKxXynD-gSzASNkwpuUhOSrlEYAJUN0ncigEdEZIsSDzbU4Tpk3whbroxucSCg09xikMAXt6d3vFqKszGtNvHOkqpI3LvzDTIWW6zdgHP4W4phn9nDNGjzQNNMQpuwfcuil46h_S6OI6JO-yD7EWHJOPgxsLfn45l-T-8vvdxc_m-ubH1cX5deNlq6ZGtYJD20vJ2lWrtDB8YIY5jZyBRK-7oWsZw06C195oobwBrWTXKym8Y0Ysyem-d5vT04xlsptQPI71O5jmYrlUou2krNkl-foP-pjmXDeyo7QQkhu-K-R7yudUSsbBbnOoC3m2DOxOit1LsVWK_SvFQg2dvFTPqw32b5FXCxUQe6DUUVxjfn_7P7V_APjXlt4</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Yu, Wen-Long</creator><creator>Yu, Guanzhen</creator><creator>Dong, Hui</creator><creator>Chen, Ke</creator><creator>Xie, Jun</creator><creator>Yu, Hua</creator><creator>Ji, Yuan</creator><creator>Yang, Guang-Shun</creator><creator>Li, Ai-Jun</creator><creator>Cong, Wen-Ming</creator><creator>Jin, Guang-Zhi</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-8961-4196</orcidid></search><sort><creationdate>20201201</creationdate><title>Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma</title><author>Yu, Wen-Long ; Yu, Guanzhen ; Dong, Hui ; Chen, Ke ; Xie, Jun ; Yu, Hua ; Ji, Yuan ; Yang, Guang-Shun ; Li, Ai-Jun ; Cong, Wen-Ming ; Jin, Guang-Zhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c465t-563206d4416b657392f191a7e2104ec78f8611e840c7c9735c907548d543ca193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Abdominal Surgery</topic><topic>Biliary Tract</topic><topic>Bioinformatics</topic><topic>Cell migration</topic><topic>Cholangiocarcinoma</topic><topic>Colorectal Surgery</topic><topic>Gastroenterology</topic><topic>Hepatology</topic><topic>Immunohistochemistry</topic><topic>Liver cancer</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Nomograms</topic><topic>Original Article—Liver</topic><topic>Pancreas</topic><topic>Prediction models</topic><topic>Proteomics</topic><topic>Risk groups</topic><topic>Surgery</topic><topic>Surgical Oncology</topic><topic>Tumor markers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yu, Wen-Long</creatorcontrib><creatorcontrib>Yu, Guanzhen</creatorcontrib><creatorcontrib>Dong, Hui</creatorcontrib><creatorcontrib>Chen, Ke</creatorcontrib><creatorcontrib>Xie, Jun</creatorcontrib><creatorcontrib>Yu, Hua</creatorcontrib><creatorcontrib>Ji, Yuan</creatorcontrib><creatorcontrib>Yang, Guang-Shun</creatorcontrib><creatorcontrib>Li, Ai-Jun</creatorcontrib><creatorcontrib>Cong, Wen-Ming</creatorcontrib><creatorcontrib>Jin, Guang-Zhi</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Immunology Abstracts</collection><collection>ProQuest Health and Medical</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>Journal of gastroenterology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yu, Wen-Long</au><au>Yu, Guanzhen</au><au>Dong, Hui</au><au>Chen, Ke</au><au>Xie, Jun</au><au>Yu, Hua</au><au>Ji, Yuan</au><au>Yang, Guang-Shun</au><au>Li, Ai-Jun</au><au>Cong, Wen-Ming</au><au>Jin, Guang-Zhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma</atitle><jtitle>Journal of gastroenterology</jtitle><stitle>J Gastroenterol</stitle><addtitle>J Gastroenterol</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>55</volume><issue>12</issue><spage>1171</spage><epage>1182</epage><pages>1171-1182</pages><issn>0944-1174</issn><eissn>1435-5922</eissn><abstract>Background
Intrahepatic cholangiocarcinoma (ICC) is the second most common tumor in primary liver cancer, but the prognostic factors associated with long-term outcomes after surgical resection remain poorly defined. This study aimed to develop a novel prognostic classifier for patients with ICC after surgery.
Methods
Using a proteomics approach, we screened tumor markers that up-regulated in ICC tissues, and narrowed down by bioinformatics analysis, western blot and immunohistochemistry. Prognostic markers were identified using Cox regression analyses in primary training cohort and the predictive models for time to recurrence (TTR) were established. The predictive accuracy of predictive model was validated in external validation cohort and prospective validation cohort. MTT assay, clonal formation assay and trans-well assays were used to verify the effect on the proliferation and migration in ICC cell line.
Results
Triosephosphate isomerise (TPI1) was significantly up-regulated in ICC tissues and Kaplan–Meier analysis reveals that higher TPI1 expression was strongly correlated with higher recurrence rate of ICC patients. In the primary training cohort, mean TTR was significantly longer (
p
< 0.0001) than in the low-risk group (26.9 months for TTR, 95% CI 22.4–31.5) than in the high-risk group (14.5 months for TTR, 95% CI 10.6–18.4). Similar results were observed in two validation cohorts. In addition, a nomogram to predict recurrence was developed. Moreover, Knockdown of TPI1 by shRNA inhibited ICC cell growth, colony information, migration, invasion in vitro.
Conclusions
Current prognostic models were accurate in predicting recurrence for ICC patients after surgical resection.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33089343</pmid><doi>10.1007/s00535-020-01729-0</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-8961-4196</orcidid></addata></record> |
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subjects | Abdominal Surgery Biliary Tract Bioinformatics Cell migration Cholangiocarcinoma Colorectal Surgery Gastroenterology Hepatology Immunohistochemistry Liver cancer Medicine Medicine & Public Health Nomograms Original Article—Liver Pancreas Prediction models Proteomics Risk groups Surgery Surgical Oncology Tumor markers |
title | Proteomics analysis identified TPI1 as a novel biomarker for predicting recurrence of intrahepatic cholangiocarcinoma |
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