Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy
In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in resid...
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| Veröffentlicht in: | Oncology reports 2009-10, Vol.22 (4), p.805-813 |
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| creator | AZEVEDO KOIKE FOLGUEIRA, Maria Aparecida BRENTANI, Helena MOURAO, Mario FIGARO CALDEIRA, José Roberto MITZI BRENTANI, Maria CARRARO, Dirce Maria DE CAMARGO BARROS, Mateus HIRATA KATAYAMA, Maria Lucia SANTANA DE ABREU, Ana Paula MANTOVANI BARBOSA, Edson TOSELLO DE OLIVEIRA, Celia PATRAO, Diogo F. C MOTA, Louise D |
| description | In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR |
| doi_str_mv | 10.3892/or_00000503 |
| format | Article |
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C ; MOTA, Louise D</creator><creatorcontrib>AZEVEDO KOIKE FOLGUEIRA, Maria Aparecida ; BRENTANI, Helena ; MOURAO, Mario ; FIGARO CALDEIRA, José Roberto ; MITZI BRENTANI, Maria ; CARRARO, Dirce Maria ; DE CAMARGO BARROS, Mateus ; HIRATA KATAYAMA, Maria Lucia ; SANTANA DE ABREU, Ana Paula ; MANTOVANI BARBOSA, Edson ; TOSELLO DE OLIVEIRA, Celia ; PATRAO, Diogo F. C ; MOTA, Louise D</creatorcontrib><description>In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of 11 patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or_00000503</identifier><identifier>PMID: 19724859</identifier><language>eng</language><publisher>Athens: Spandidos</publisher><subject>Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biological and medical sciences ; Biomarkers, Tumor - genetics ; Breast Neoplasms - drug therapy ; Breast Neoplasms - genetics ; Connective Tissue Growth Factor - biosynthesis ; Connective Tissue Growth Factor - drug effects ; Connective Tissue Growth Factor - genetics ; Cyclophosphamide - administration & dosage ; Doxorubicin - administration & dosage ; Drug Resistance, Neoplasm - genetics ; Dual Specificity Phosphatase 1 - biosynthesis ; Dual Specificity Phosphatase 1 - drug effects ; Dual Specificity Phosphatase 1 - genetics ; Female ; Gene Expression - drug effects ; Gene Expression Profiling ; Gynecology. 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Obstetrics ; Humans ; Mammary gland diseases ; MAP Kinase Kinase 4 - metabolism ; Medical sciences ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm, Residual ; Oligonucleotide Array Sequence Analysis ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction - genetics ; Tumors</subject><ispartof>Oncology reports, 2009-10, Vol.22 (4), p.805-813</ispartof><rights>2009 INIST-CNRS</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c354t-ac7a84ac3cf9ad6be04643c9e21e28f2103917c9c47e46f1598dfdc886ce97363</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21942986$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19724859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>AZEVEDO KOIKE FOLGUEIRA, Maria Aparecida</creatorcontrib><creatorcontrib>BRENTANI, Helena</creatorcontrib><creatorcontrib>MOURAO, Mario</creatorcontrib><creatorcontrib>FIGARO CALDEIRA, José Roberto</creatorcontrib><creatorcontrib>MITZI BRENTANI, Maria</creatorcontrib><creatorcontrib>CARRARO, Dirce Maria</creatorcontrib><creatorcontrib>DE CAMARGO BARROS, Mateus</creatorcontrib><creatorcontrib>HIRATA KATAYAMA, Maria Lucia</creatorcontrib><creatorcontrib>SANTANA DE ABREU, Ana Paula</creatorcontrib><creatorcontrib>MANTOVANI BARBOSA, Edson</creatorcontrib><creatorcontrib>TOSELLO DE OLIVEIRA, Celia</creatorcontrib><creatorcontrib>PATRAO, Diogo F. C</creatorcontrib><creatorcontrib>MOTA, Louise D</creatorcontrib><title>Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of 11 patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.</description><subject>Adult</subject><subject>Aged</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - genetics</subject><subject>Connective Tissue Growth Factor - biosynthesis</subject><subject>Connective Tissue Growth Factor - drug effects</subject><subject>Connective Tissue Growth Factor - genetics</subject><subject>Cyclophosphamide - administration & dosage</subject><subject>Doxorubicin - administration & dosage</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Dual Specificity Phosphatase 1 - biosynthesis</subject><subject>Dual Specificity Phosphatase 1 - drug effects</subject><subject>Dual Specificity Phosphatase 1 - genetics</subject><subject>Female</subject><subject>Gene Expression - drug effects</subject><subject>Gene Expression Profiling</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>Humans</subject><subject>Mammary gland diseases</subject><subject>MAP Kinase Kinase 4 - metabolism</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Neoadjuvant Therapy</subject><subject>Neoplasm, Residual</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Signal Transduction - genetics</subject><subject>Tumors</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpNkE1Lw0AQhhdRbK2evMtePEl0v_KxRylahYIXBW9hsjtLUtJs3E2l_femtKhzmHkZnpnDQ8g1Z_ey0OLBh5LtK2XyhEx5rnkilOSnY2aCJ1KmnxNyEeOKMZGzTJ-TCde5UEWqp-RrgR1S3PYBY2x8R_vgXdMi9Y6Oq8ZuoKVVQIgDNdAZDBTcMHbrtz5sqsY0HYXOUrMzre9rH_sa1o1F2qEHu9p8Qzde1rj2Q40B-t0lOXPQRrw6zhn5eH56n78ky7fF6_xxmRiZqiEBk0OhwEjjNNisQqYyJY1GwVEUTnAmNc-NNipHlTme6sI6a4oiM6hzmckZuTv8NcHHGNCVfWjWEHYlZ-VeXPlP3EjfHOh-U63R_rFHUyNwewQgGmhdGGU08ZcTXCuhi0z-APW_eVA</recordid><startdate>20091001</startdate><enddate>20091001</enddate><creator>AZEVEDO KOIKE FOLGUEIRA, Maria Aparecida</creator><creator>BRENTANI, Helena</creator><creator>MOURAO, Mario</creator><creator>FIGARO CALDEIRA, José Roberto</creator><creator>MITZI BRENTANI, Maria</creator><creator>CARRARO, Dirce Maria</creator><creator>DE CAMARGO BARROS, Mateus</creator><creator>HIRATA KATAYAMA, Maria Lucia</creator><creator>SANTANA DE ABREU, Ana Paula</creator><creator>MANTOVANI BARBOSA, Edson</creator><creator>TOSELLO DE OLIVEIRA, Celia</creator><creator>PATRAO, Diogo F. 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Andrology. Obstetrics</topic><topic>Humans</topic><topic>Mammary gland diseases</topic><topic>MAP Kinase Kinase 4 - metabolism</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Neoadjuvant Therapy</topic><topic>Neoplasm, Residual</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Signal Transduction - genetics</topic><topic>Tumors</topic><toplevel>online_resources</toplevel><creatorcontrib>AZEVEDO KOIKE FOLGUEIRA, Maria Aparecida</creatorcontrib><creatorcontrib>BRENTANI, Helena</creatorcontrib><creatorcontrib>MOURAO, Mario</creatorcontrib><creatorcontrib>FIGARO CALDEIRA, José Roberto</creatorcontrib><creatorcontrib>MITZI BRENTANI, Maria</creatorcontrib><creatorcontrib>CARRARO, Dirce Maria</creatorcontrib><creatorcontrib>DE CAMARGO BARROS, Mateus</creatorcontrib><creatorcontrib>HIRATA KATAYAMA, Maria Lucia</creatorcontrib><creatorcontrib>SANTANA DE ABREU, Ana Paula</creatorcontrib><creatorcontrib>MANTOVANI BARBOSA, Edson</creatorcontrib><creatorcontrib>TOSELLO DE OLIVEIRA, Celia</creatorcontrib><creatorcontrib>PATRAO, Diogo F. 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Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of 11 patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.</abstract><cop>Athens</cop><pub>Spandidos</pub><pmid>19724859</pmid><doi>10.3892/or_00000503</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Oncology reports, 2009-10, Vol.22 (4), p.805-813 |
| issn | 1021-335X 1791-2431 |
| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biological and medical sciences Biomarkers, Tumor - genetics Breast Neoplasms - drug therapy Breast Neoplasms - genetics Connective Tissue Growth Factor - biosynthesis Connective Tissue Growth Factor - drug effects Connective Tissue Growth Factor - genetics Cyclophosphamide - administration & dosage Doxorubicin - administration & dosage Drug Resistance, Neoplasm - genetics Dual Specificity Phosphatase 1 - biosynthesis Dual Specificity Phosphatase 1 - drug effects Dual Specificity Phosphatase 1 - genetics Female Gene Expression - drug effects Gene Expression Profiling Gynecology. Andrology. Obstetrics Humans Mammary gland diseases MAP Kinase Kinase 4 - metabolism Medical sciences Middle Aged Neoadjuvant Therapy Neoplasm, Residual Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction Signal Transduction - genetics Tumors |
| title | Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy |
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