Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy
Cyclophosphamide, methotrexate and 5-fluorouracile (CMF)-based chemotherapy for adjuvant treatment of breast cancer reduces the risk of relapse. In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChi...
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| Veröffentlicht in: | Breast cancer research and treatment 2009-11, Vol.118 (1), p.45-56 |
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| creator | Specht, Katja Harbeck, Nadia Smida, Jan Annecke, Katja Reich, Ulrike Naehrig, Joerg Langer, Rupert Mages, Joerg Busch, Raymonde Kruse, Elisabeth Klein-Hitpass, Ludger Schmitt, Manfred Kiechle, Marion Hoefler, Heinz |
| description | Cyclophosphamide, methotrexate and 5-fluorouracile (CMF)-based chemotherapy for adjuvant treatment of breast cancer reduces the risk of relapse. In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChips, RNA samples from 19 patients with primary breast cancer who had been uniformly treated with adjuvant CMF chemotherapy were analyzed. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. An additional independent validation set of 51 patients and 21 genes were analyzed by quantitative RT-PCR. Applying different algorithms to evaluate our microarray data, we identified two gene expression signatures of 21 and 12 genes containing eight overlapping genes, that predict recurrence in 19 cases with high accuracy (94%). Quantitative RT-PCR demonstrated that six genes from the combined signatures (CXCL9, ITSN2, GNAI2, H2AFX, INDO, and MGC10986) were significantly differentially expressed in the recurrence versus the non-recurrence group of the 19 cases and the independent breast cancer patient cohort (n = 51) treated with CMF. High expression levels of CXCL9, ITSN2, and GNAI2 were associated with prolonged disease-free survival (DFS) (P = 0.029, 0.018 and 0.032, respectively). When patients were stratified by combined CXCL9/ITSN2 or CXCL9/FLJ22028 tumor levels, they exhibited significantly different disease-free survival curves (P = 0.0073 and P = 0.005, respectively). Finally, the CXCL9/ITSN2 and CXCL9/FLJ22028 ratio was an independent prognostic factor (P = 0.034 and P = 0.003, respectively) for DFS by multivariate Cox analysis in the 70-patient cohort. Our data highlight the feasibility of a prognostic assay that is applicable to therapeutic decision-making for breast cancer. Whether the biomarker profile is chemotherapy-specific or whether it is a more general indicator of bad prognosis of breast cancer patients remains to be explored. |
| doi_str_mv | 10.1007/s10549-008-0207-y |
| format | Article |
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In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChips, RNA samples from 19 patients with primary breast cancer who had been uniformly treated with adjuvant CMF chemotherapy were analyzed. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. An additional independent validation set of 51 patients and 21 genes were analyzed by quantitative RT-PCR. Applying different algorithms to evaluate our microarray data, we identified two gene expression signatures of 21 and 12 genes containing eight overlapping genes, that predict recurrence in 19 cases with high accuracy (94%). Quantitative RT-PCR demonstrated that six genes from the combined signatures (CXCL9, ITSN2, GNAI2, H2AFX, INDO, and MGC10986) were significantly differentially expressed in the recurrence versus the non-recurrence group of the 19 cases and the independent breast cancer patient cohort (n = 51) treated with CMF. High expression levels of CXCL9, ITSN2, and GNAI2 were associated with prolonged disease-free survival (DFS) (P = 0.029, 0.018 and 0.032, respectively). When patients were stratified by combined CXCL9/ITSN2 or CXCL9/FLJ22028 tumor levels, they exhibited significantly different disease-free survival curves (P = 0.0073 and P = 0.005, respectively). Finally, the CXCL9/ITSN2 and CXCL9/FLJ22028 ratio was an independent prognostic factor (P = 0.034 and P = 0.003, respectively) for DFS by multivariate Cox analysis in the 70-patient cohort. Our data highlight the feasibility of a prognostic assay that is applicable to therapeutic decision-making for breast cancer. Whether the biomarker profile is chemotherapy-specific or whether it is a more general indicator of bad prognosis of breast cancer patients remains to be explored.</description><identifier>ISSN: 0167-6806</identifier><identifier>EISSN: 1573-7217</identifier><identifier>DOI: 10.1007/s10549-008-0207-y</identifier><identifier>PMID: 18925433</identifier><identifier>CODEN: BCTRD6</identifier><language>eng</language><publisher>Boston: Boston : Springer US</publisher><subject>Adaptor Proteins, Vesicular Transport - biosynthesis ; Adaptor Proteins, Vesicular Transport - genetics ; Adult ; Aged ; Algorithms ; Antineoplastic Combined Chemotherapy Protocols - administration & dosage ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Breast cancer ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Breast Neoplasms - mortality ; Breast Neoplasms - surgery ; Cancer research ; Cancer therapies ; Carcinoma - drug therapy ; Carcinoma - genetics ; Carcinoma - mortality ; Carcinoma - surgery ; Chemokine CXCL9 - biosynthesis ; Chemokine CXCL9 - genetics ; Chemotherapy ; Chemotherapy, Adjuvant ; Combined Modality Therapy ; Cyclophosphamide - administration & dosage ; Disease-Free Survival ; Feasibility Studies ; Female ; Fluorouracil - administration & dosage ; Follow-Up Studies ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; GTP-Binding Protein alpha Subunit, Gi2 - biosynthesis ; GTP-Binding Protein alpha Subunit, Gi2 - genetics ; Gynecology. Andrology. Obstetrics ; Histones - biosynthesis ; Histones - genetics ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis ; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics ; Mammary gland diseases ; Mastectomy ; Medical prognosis ; Medical sciences ; Medicine ; Medicine & Public Health ; Methotrexate - administration & dosage ; Middle Aged ; Molecular biology ; Neoplasm Proteins - biosynthesis ; Neoplasm Proteins - genetics ; Oligonucleotide Array Sequence Analysis ; Oncology ; Preclinical Study ; Recurrence ; RNA, Messenger - genetics ; RNA, Neoplasm - genetics ; Tumors</subject><ispartof>Breast cancer research and treatment, 2009-11, Vol.118 (1), p.45-56</ispartof><rights>Springer Science+Business Media, LLC. 2008</rights><rights>2009 INIST-CNRS</rights><rights>Springer Science+Business Media, LLC. 2009</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c532t-e43d2aa24cc700898e8604a4f42a0152cd47f8b5505edfd1e2e182e55ccf14e43</citedby><cites>FETCH-LOGICAL-c532t-e43d2aa24cc700898e8604a4f42a0152cd47f8b5505edfd1e2e182e55ccf14e43</cites><orcidid>0000-0002-9744-7372</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/s10549-008-0207-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10549-008-0207-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22109162$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18925433$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-00478272$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Specht, Katja</creatorcontrib><creatorcontrib>Harbeck, Nadia</creatorcontrib><creatorcontrib>Smida, Jan</creatorcontrib><creatorcontrib>Annecke, Katja</creatorcontrib><creatorcontrib>Reich, Ulrike</creatorcontrib><creatorcontrib>Naehrig, Joerg</creatorcontrib><creatorcontrib>Langer, Rupert</creatorcontrib><creatorcontrib>Mages, Joerg</creatorcontrib><creatorcontrib>Busch, Raymonde</creatorcontrib><creatorcontrib>Kruse, Elisabeth</creatorcontrib><creatorcontrib>Klein-Hitpass, Ludger</creatorcontrib><creatorcontrib>Schmitt, Manfred</creatorcontrib><creatorcontrib>Kiechle, Marion</creatorcontrib><creatorcontrib>Hoefler, Heinz</creatorcontrib><title>Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy</title><title>Breast cancer research and treatment</title><addtitle>Breast Cancer Res Treat</addtitle><addtitle>Breast Cancer Res Treat</addtitle><description>Cyclophosphamide, methotrexate and 5-fluorouracile (CMF)-based chemotherapy for adjuvant treatment of breast cancer reduces the risk of relapse. In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChips, RNA samples from 19 patients with primary breast cancer who had been uniformly treated with adjuvant CMF chemotherapy were analyzed. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. An additional independent validation set of 51 patients and 21 genes were analyzed by quantitative RT-PCR. Applying different algorithms to evaluate our microarray data, we identified two gene expression signatures of 21 and 12 genes containing eight overlapping genes, that predict recurrence in 19 cases with high accuracy (94%). Quantitative RT-PCR demonstrated that six genes from the combined signatures (CXCL9, ITSN2, GNAI2, H2AFX, INDO, and MGC10986) were significantly differentially expressed in the recurrence versus the non-recurrence group of the 19 cases and the independent breast cancer patient cohort (n = 51) treated with CMF. High expression levels of CXCL9, ITSN2, and GNAI2 were associated with prolonged disease-free survival (DFS) (P = 0.029, 0.018 and 0.032, respectively). When patients were stratified by combined CXCL9/ITSN2 or CXCL9/FLJ22028 tumor levels, they exhibited significantly different disease-free survival curves (P = 0.0073 and P = 0.005, respectively). Finally, the CXCL9/ITSN2 and CXCL9/FLJ22028 ratio was an independent prognostic factor (P = 0.034 and P = 0.003, respectively) for DFS by multivariate Cox analysis in the 70-patient cohort. Our data highlight the feasibility of a prognostic assay that is applicable to therapeutic decision-making for breast cancer. Whether the biomarker profile is chemotherapy-specific or whether it is a more general indicator of bad prognosis of breast cancer patients remains to be explored.</description><subject>Adaptor Proteins, Vesicular Transport - biosynthesis</subject><subject>Adaptor Proteins, Vesicular Transport - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Algorithms</subject><subject>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - mortality</subject><subject>Breast Neoplasms - surgery</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Carcinoma - drug therapy</subject><subject>Carcinoma - genetics</subject><subject>Carcinoma - mortality</subject><subject>Carcinoma - surgery</subject><subject>Chemokine CXCL9 - biosynthesis</subject><subject>Chemokine CXCL9 - genetics</subject><subject>Chemotherapy</subject><subject>Chemotherapy, Adjuvant</subject><subject>Combined Modality Therapy</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Disease-Free Survival</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Fluorouracil - administration & dosage</subject><subject>Follow-Up Studies</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>GTP-Binding Protein alpha Subunit, Gi2 - biosynthesis</subject><subject>GTP-Binding Protein alpha Subunit, Gi2 - genetics</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Histones - biosynthesis</subject><subject>Histones - genetics</subject><subject>Humans</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis</subject><subject>Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics</subject><subject>Mammary gland diseases</subject><subject>Mastectomy</subject><subject>Medical prognosis</subject><subject>Medical sciences</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Methotrexate - administration & dosage</subject><subject>Middle Aged</subject><subject>Molecular biology</subject><subject>Neoplasm Proteins - biosynthesis</subject><subject>Neoplasm Proteins - genetics</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncology</subject><subject>Preclinical Study</subject><subject>Recurrence</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Neoplasm - genetics</subject><subject>Tumors</subject><issn>0167-6806</issn><issn>1573-7217</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9ksFu1DAQhiMEoqXwAFwgqgSIQ2Ds2LFzrFYtRVrEAXq2vM5416tssthOxb49s8qqlTj0MpY93z-e8e-ieMvgCwNQXxMDKdoKQFfAQVWHZ8U5k6quFGfqeXEOrFFVo6E5K16ltAWAVkH7sjhjuuVS1PV5ka__7iOmFMah3MfRhz4M6zJ0OOTgA6ZyjQPFvLGZ8tgFl8uIbooRB4fl6MtVRJty6SztY2l9PsZuO93bIZeLHzfVyibsSrfB3Zg3GO3-8Lp44W2f8M1pvSjubq5_L26r5c9v3xdXy8rJmucKRd1xa7lwTtGMrUbdgLDCC26BSe46obxeSQkSO98x5Mg0Rymd80yQ-qL4PNfd2N7sY9jZeDCjDeb2ammOZwBCaa74PSP208zSK_yZMGWzC8lh39sBxykZVQsgtJVEfnyS5Iwp1jZA4OV_4Hac4kATE8OFEkLXBLEZcnFMKaJ_aJSBObpsZpepV22OLpsDad6dCk-rHXaPipOtBHw4ATY52_tI5oT0wHHOoGUNJ47PXKLUsMb42OFTt7-fRd6Oxq4jFb77xYHV9N1azmtR_wNEB8i0</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Specht, Katja</creator><creator>Harbeck, Nadia</creator><creator>Smida, Jan</creator><creator>Annecke, Katja</creator><creator>Reich, Ulrike</creator><creator>Naehrig, Joerg</creator><creator>Langer, Rupert</creator><creator>Mages, Joerg</creator><creator>Busch, Raymonde</creator><creator>Kruse, Elisabeth</creator><creator>Klein-Hitpass, Ludger</creator><creator>Schmitt, Manfred</creator><creator>Kiechle, Marion</creator><creator>Hoefler, Heinz</creator><general>Boston : Springer US</general><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</general><general>Springer Verlag</general><scope>FBQ</scope><scope>IQODW</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>K9.</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><orcidid>https://orcid.org/0000-0002-9744-7372</orcidid></search><sort><creationdate>20091101</creationdate><title>Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy</title><author>Specht, Katja ; Harbeck, Nadia ; Smida, Jan ; Annecke, Katja ; Reich, Ulrike ; Naehrig, Joerg ; Langer, Rupert ; Mages, Joerg ; Busch, Raymonde ; Kruse, Elisabeth ; Klein-Hitpass, Ludger ; Schmitt, Manfred ; Kiechle, Marion ; Hoefler, Heinz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c532t-e43d2aa24cc700898e8604a4f42a0152cd47f8b5505edfd1e2e182e55ccf14e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adaptor Proteins, Vesicular Transport - biosynthesis</topic><topic>Adaptor Proteins, Vesicular Transport - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Algorithms</topic><topic>Antineoplastic Combined Chemotherapy Protocols - administration & dosage</topic><topic>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - mortality</topic><topic>Breast Neoplasms - surgery</topic><topic>Cancer research</topic><topic>Cancer therapies</topic><topic>Carcinoma - drug therapy</topic><topic>Carcinoma - genetics</topic><topic>Carcinoma - mortality</topic><topic>Carcinoma - surgery</topic><topic>Chemokine CXCL9 - biosynthesis</topic><topic>Chemokine CXCL9 - genetics</topic><topic>Chemotherapy</topic><topic>Chemotherapy, Adjuvant</topic><topic>Combined Modality Therapy</topic><topic>Cyclophosphamide - administration & dosage</topic><topic>Disease-Free Survival</topic><topic>Feasibility Studies</topic><topic>Female</topic><topic>Fluorouracil - administration & dosage</topic><topic>Follow-Up Studies</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>GTP-Binding Protein alpha Subunit, Gi2 - biosynthesis</topic><topic>GTP-Binding Protein alpha Subunit, Gi2 - genetics</topic><topic>Gynecology. Andrology. Obstetrics</topic><topic>Histones - biosynthesis</topic><topic>Histones - genetics</topic><topic>Humans</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis</topic><topic>Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics</topic><topic>Mammary gland diseases</topic><topic>Mastectomy</topic><topic>Medical prognosis</topic><topic>Medical sciences</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Methotrexate - administration & dosage</topic><topic>Middle Aged</topic><topic>Molecular biology</topic><topic>Neoplasm Proteins - biosynthesis</topic><topic>Neoplasm Proteins - genetics</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Oncology</topic><topic>Preclinical Study</topic><topic>Recurrence</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Neoplasm - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Specht, Katja</creatorcontrib><creatorcontrib>Harbeck, Nadia</creatorcontrib><creatorcontrib>Smida, Jan</creatorcontrib><creatorcontrib>Annecke, Katja</creatorcontrib><creatorcontrib>Reich, Ulrike</creatorcontrib><creatorcontrib>Naehrig, Joerg</creatorcontrib><creatorcontrib>Langer, Rupert</creatorcontrib><creatorcontrib>Mages, Joerg</creatorcontrib><creatorcontrib>Busch, Raymonde</creatorcontrib><creatorcontrib>Kruse, Elisabeth</creatorcontrib><creatorcontrib>Klein-Hitpass, Ludger</creatorcontrib><creatorcontrib>Schmitt, Manfred</creatorcontrib><creatorcontrib>Kiechle, Marion</creatorcontrib><creatorcontrib>Hoefler, Heinz</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</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>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Consumer Health Database</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 Basic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><jtitle>Breast cancer research and treatment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Specht, Katja</au><au>Harbeck, Nadia</au><au>Smida, Jan</au><au>Annecke, Katja</au><au>Reich, Ulrike</au><au>Naehrig, Joerg</au><au>Langer, Rupert</au><au>Mages, Joerg</au><au>Busch, Raymonde</au><au>Kruse, Elisabeth</au><au>Klein-Hitpass, Ludger</au><au>Schmitt, Manfred</au><au>Kiechle, Marion</au><au>Hoefler, Heinz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy</atitle><jtitle>Breast cancer research and treatment</jtitle><stitle>Breast Cancer Res Treat</stitle><addtitle>Breast Cancer Res Treat</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>118</volume><issue>1</issue><spage>45</spage><epage>56</epage><pages>45-56</pages><issn>0167-6806</issn><eissn>1573-7217</eissn><coden>BCTRD6</coden><abstract>Cyclophosphamide, methotrexate and 5-fluorouracile (CMF)-based chemotherapy for adjuvant treatment of breast cancer reduces the risk of relapse. In this exploratory study, we tested the feasibility of identifying molecular markers of recurrence in CMF-treated patients. Using Affymetrix U133A GeneChips, RNA samples from 19 patients with primary breast cancer who had been uniformly treated with adjuvant CMF chemotherapy were analyzed. Two supervised class prediction approaches were used to identify gene markers that can best discriminate between patients who would experience relapse and patients who would remain disease-free. An additional independent validation set of 51 patients and 21 genes were analyzed by quantitative RT-PCR. Applying different algorithms to evaluate our microarray data, we identified two gene expression signatures of 21 and 12 genes containing eight overlapping genes, that predict recurrence in 19 cases with high accuracy (94%). Quantitative RT-PCR demonstrated that six genes from the combined signatures (CXCL9, ITSN2, GNAI2, H2AFX, INDO, and MGC10986) were significantly differentially expressed in the recurrence versus the non-recurrence group of the 19 cases and the independent breast cancer patient cohort (n = 51) treated with CMF. High expression levels of CXCL9, ITSN2, and GNAI2 were associated with prolonged disease-free survival (DFS) (P = 0.029, 0.018 and 0.032, respectively). When patients were stratified by combined CXCL9/ITSN2 or CXCL9/FLJ22028 tumor levels, they exhibited significantly different disease-free survival curves (P = 0.0073 and P = 0.005, respectively). Finally, the CXCL9/ITSN2 and CXCL9/FLJ22028 ratio was an independent prognostic factor (P = 0.034 and P = 0.003, respectively) for DFS by multivariate Cox analysis in the 70-patient cohort. Our data highlight the feasibility of a prognostic assay that is applicable to therapeutic decision-making for breast cancer. Whether the biomarker profile is chemotherapy-specific or whether it is a more general indicator of bad prognosis of breast cancer patients remains to be explored.</abstract><cop>Boston</cop><pub>Boston : Springer US</pub><pmid>18925433</pmid><doi>10.1007/s10549-008-0207-y</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-9744-7372</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0167-6806 |
| ispartof | Breast cancer research and treatment, 2009-11, Vol.118 (1), p.45-56 |
| issn | 0167-6806 1573-7217 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_00478272v1 |
| source | MEDLINE; Springer Nature - Complete Springer Journals |
| subjects | Adaptor Proteins, Vesicular Transport - biosynthesis Adaptor Proteins, Vesicular Transport - genetics Adult Aged Algorithms Antineoplastic Combined Chemotherapy Protocols - administration & dosage Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - mortality Breast Neoplasms - surgery Cancer research Cancer therapies Carcinoma - drug therapy Carcinoma - genetics Carcinoma - mortality Carcinoma - surgery Chemokine CXCL9 - biosynthesis Chemokine CXCL9 - genetics Chemotherapy Chemotherapy, Adjuvant Combined Modality Therapy Cyclophosphamide - administration & dosage Disease-Free Survival Feasibility Studies Female Fluorouracil - administration & dosage Follow-Up Studies Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic GTP-Binding Protein alpha Subunit, Gi2 - biosynthesis GTP-Binding Protein alpha Subunit, Gi2 - genetics Gynecology. Andrology. Obstetrics Histones - biosynthesis Histones - genetics Humans Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics Mammary gland diseases Mastectomy Medical prognosis Medical sciences Medicine Medicine & Public Health Methotrexate - administration & dosage Middle Aged Molecular biology Neoplasm Proteins - biosynthesis Neoplasm Proteins - genetics Oligonucleotide Array Sequence Analysis Oncology Preclinical Study Recurrence RNA, Messenger - genetics RNA, Neoplasm - genetics Tumors |
| title | Expression profiling identifies genes that predict recurrence of breast cancer after adjuvant CMF-based chemotherapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T10%3A22%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20profiling%20identifies%20genes%20that%20predict%20recurrence%20of%20breast%20cancer%20after%20adjuvant%20CMF-based%20chemotherapy&rft.jtitle=Breast%20cancer%20research%20and%20treatment&rft.au=Specht,%20Katja&rft.date=2009-11-01&rft.volume=118&rft.issue=1&rft.spage=45&rft.epage=56&rft.pages=45-56&rft.issn=0167-6806&rft.eissn=1573-7217&rft.coden=BCTRD6&rft_id=info:doi/10.1007/s10549-008-0207-y&rft_dat=%3Cproquest_hal_p%3E1880520291%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=212474483&rft_id=info:pmid/18925433&rfr_iscdi=true |