Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis

Background Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurren...

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Veröffentlicht in:Annals of surgical oncology 2012-02, Vol.19 (2), p.402-408
Hauptverfasser: Pilati, Pierluigi, Mocellin, Simone, Bertazza, Loris, Galdi, Francesca, Briarava, Marta, Mammano, Enzo, Tessari, Emanuela, Zavagno, Giorgio, Nitti, Donato
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container_title Annals of surgical oncology
container_volume 19
creator Pilati, Pierluigi
Mocellin, Simone
Bertazza, Loris
Galdi, Francesca
Briarava, Marta
Mammano, Enzo
Tessari, Emanuela
Zavagno, Giorgio
Nitti, Donato
description Background Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. Methods We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. Results Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9–3.7, P  
doi_str_mv 10.1245/s10434-011-2132-2
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We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. Methods We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. Results Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9–3.7, P  &lt; 0.0001; and hazard ratio 2.1, 95% CI 1.4–3.2, P  &lt; 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9–3.6, P  &lt; 0.0001), indicating that this biomarker can independently predict the survival of these patients. Conclusions CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.</description><identifier>ISSN: 1068-9265</identifier><identifier>EISSN: 1534-4681</identifier><identifier>DOI: 10.1245/s10434-011-2132-2</identifier><identifier>PMID: 22071867</identifier><language>eng</language><publisher>New York: Springer-Verlag</publisher><subject>Aged ; Biomarkers, Tumor - genetics ; Biomarkers, Tumor - metabolism ; Colorectal Cancer ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - pathology ; Colorectal Neoplasms - surgery ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Neoplasms - mortality ; Liver Neoplasms - secondary ; Liver Neoplasms - surgery ; Lymphatic Metastasis ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Neoplasm Recurrence, Local - diagnosis ; Neoplasm Recurrence, Local - mortality ; Neoplasm Recurrence, Local - surgery ; Neoplasm Staging ; Neoplastic Cells, Circulating - metabolism ; Neoplastic Cells, Circulating - pathology ; Neoplastic Stem Cells - metabolism ; Neoplastic Stem Cells - pathology ; Oncology ; Prognosis ; Real-Time Polymerase Chain Reaction ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction ; Surgery ; Surgical Oncology ; Survival Rate</subject><ispartof>Annals of surgical oncology, 2012-02, Vol.19 (2), p.402-408</ispartof><rights>Society of Surgical Oncology 2011</rights><rights>Society of Surgical Oncology 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c469t-3c90676986bf0744c8f79b0f3aecb90ec35fa4d83dcd33445c1e8a13b8a477693</citedby><cites>FETCH-LOGICAL-c469t-3c90676986bf0744c8f79b0f3aecb90ec35fa4d83dcd33445c1e8a13b8a477693</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1245/s10434-011-2132-2$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1245/s10434-011-2132-2$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22071867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pilati, Pierluigi</creatorcontrib><creatorcontrib>Mocellin, Simone</creatorcontrib><creatorcontrib>Bertazza, Loris</creatorcontrib><creatorcontrib>Galdi, Francesca</creatorcontrib><creatorcontrib>Briarava, Marta</creatorcontrib><creatorcontrib>Mammano, Enzo</creatorcontrib><creatorcontrib>Tessari, Emanuela</creatorcontrib><creatorcontrib>Zavagno, Giorgio</creatorcontrib><creatorcontrib>Nitti, Donato</creatorcontrib><title>Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis</title><title>Annals of surgical oncology</title><addtitle>Ann Surg Oncol</addtitle><addtitle>Ann Surg Oncol</addtitle><description>Background Although surgery is the gold standard treatment of hepatic metastasis from colorectal cancer (CRC), many patients ultimately die of their disease. We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. Methods We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. Results Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9–3.7, P  &lt; 0.0001; and hazard ratio 2.1, 95% CI 1.4–3.2, P  &lt; 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9–3.6, P  &lt; 0.0001), indicating that this biomarker can independently predict the survival of these patients. Conclusions CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.</description><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Colorectal Cancer</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Colorectal Neoplasms - surgery</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Hepatectomy</subject><subject>Humans</subject><subject>Liver Neoplasms - mortality</subject><subject>Liver Neoplasms - secondary</subject><subject>Liver Neoplasms - surgery</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Middle Aged</subject><subject>Neoplasm Recurrence, Local - diagnosis</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Neoplasm Recurrence, Local - surgery</subject><subject>Neoplasm Staging</subject><subject>Neoplastic Cells, Circulating - metabolism</subject><subject>Neoplastic Cells, Circulating - pathology</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Oncology</subject><subject>Prognosis</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>Retrospective Studies</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Surgery</subject><subject>Surgical Oncology</subject><subject>Survival Rate</subject><issn>1068-9265</issn><issn>1534-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kUuLFDEUhYMozkN_gBsJbpxNOXlVHksp1BFabEbHbUilbjU1VCdtkhJm7R83RY8KwgiB3OR-54Sbg9ALSt5QJtrLTIngoiGUNoxy1rBH6JS29UZITR_XmkjdGCbbE3SW8y0hVHHSPkUnjBFFtVSn6Oc2xV2IuUwef3PzAjiOeLsUV6YfgLsp-WWuddjhzgUPCX8psMcdzHPGU8Db2oNQMr4JA6RdXMErOLjV7hoy-DLFgMeYcBfnmOrZzXhTrRP-BMXluqb8DD0Z3Zzh-f1-jm7ev_vaXTWbzx8-dm83jRfSlIZ7Q6SSRst-JEoIr0dlejJyB743BDxvRycGzQc_cC5E6yloR3mvnVBVx8_R66PvIcXvC-Ri91P2dRQXIC7ZGqp0qwWRlbz4L0lV_WFljFrRV_-gt3FJoc6x-nGqqWwrRI-QTzHnBKM9pGnv0p2lxK5R2mOUtkZp1ygtq5qX98ZLv4fhj-J3dhVgRyDXVthB-vvyw66_APXZqdE</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Pilati, Pierluigi</creator><creator>Mocellin, Simone</creator><creator>Bertazza, Loris</creator><creator>Galdi, Francesca</creator><creator>Briarava, Marta</creator><creator>Mammano, Enzo</creator><creator>Tessari, Emanuela</creator><creator>Zavagno, Giorgio</creator><creator>Nitti, Donato</creator><general>Springer-Verlag</general><general>Springer Nature B.V</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>3V.</scope><scope>7TO</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>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis</title><author>Pilati, Pierluigi ; 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We tested the hypothesis that the detection of circulating tumor cells (CTC) might identify patients at high risk of dying of disease recurrence after apparently radical liver surgery. Methods We considered 50 patients undergoing radical surgery for liver-confined hepatic metastasis from CRC. The expression of a panel of cancer-related genes, as assessed by quantitative real-time PCR, was used to detect CTC in the peripheral blood of these patients immediately before surgery. Survival analysis was performed by the Cox regression model. Results Univariate analysis of the expression levels of CD133 (a marker of colon cancer stem cells) and survivin (an antiapoptotic factor) resulted in statistically significant association with patient survival [hazard ratio (HR) 2.7, 95% confidence interval (CI) 1.9–3.7, P  &lt; 0.0001; and hazard ratio 2.1, 95% CI 1.4–3.2, P  &lt; 0.0001, respectively]. Remarkably, multivariate analysis found that only the transcriptional amount of CD133 resulted in statistical significance (HR 2.6, 95% CI 1.9–3.6, P  &lt; 0.0001), indicating that this biomarker can independently predict the survival of these patients. Conclusions CD133-positive CTC may represent a suitable prognostic marker to stratify the risk of patients who undergo liver resection for CRC metastasis, which opens the avenue to identifying and potentially monitoring the patients who are most likely to benefit from adjuvant treatments.</abstract><cop>New York</cop><pub>Springer-Verlag</pub><pmid>22071867</pmid><doi>10.1245/s10434-011-2132-2</doi><tpages>7</tpages></addata></record>
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subjects Aged
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Colorectal Cancer
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
Colorectal Neoplasms - surgery
Female
Follow-Up Studies
Hepatectomy
Humans
Liver Neoplasms - mortality
Liver Neoplasms - secondary
Liver Neoplasms - surgery
Lymphatic Metastasis
Male
Medicine
Medicine & Public Health
Middle Aged
Neoplasm Recurrence, Local - diagnosis
Neoplasm Recurrence, Local - mortality
Neoplasm Recurrence, Local - surgery
Neoplasm Staging
Neoplastic Cells, Circulating - metabolism
Neoplastic Cells, Circulating - pathology
Neoplastic Stem Cells - metabolism
Neoplastic Stem Cells - pathology
Oncology
Prognosis
Real-Time Polymerase Chain Reaction
Retrospective Studies
Reverse Transcriptase Polymerase Chain Reaction
Surgery
Surgical Oncology
Survival Rate
title Prognostic Value of Putative Circulating Cancer Stem Cells in Patients Undergoing Hepatic Resection for Colorectal Liver Metastasis
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