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
Hauptverfasser: 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
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container_issue 12
container_start_page 1171
container_title Journal of gastroenterology
container_volume 55
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
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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  &lt; 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 &amp; 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  &lt; 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 &amp; 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 ; 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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  &lt; 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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