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Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease
Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional changes associated with this breast cancer subtype, we applied suppression subtractive hybridisation method to analyse differentially expres...
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| Published in: | British journal of cancer 2008-09, Vol.99 (5), p.774-780 |
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| Main Authors: | , , , , , , , , , , |
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| container_end_page | 780 |
| container_issue | 5 |
| container_start_page | 774 |
| container_title | British journal of cancer |
| container_volume | 99 |
| creator | Helms, M W Kemming, D Pospisil, H Vogt, U Buerger, H Korsching, E Liedtke, C Schlotter, C M Wang, A Chan, S Y Brandt, B H |
| description | Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional changes associated with this breast cancer subtype, we applied suppression subtractive hybridisation method to analyse differentially expressed genes among six breast tumours with and without chromosomal 7p and 8q gains. Identified mRNAs were validated by real-time RT–PCR in tissue samples obtained from 186 patients with stage I/II breast cancer. Advanced statistical methods were applied to identify associations of mRNA expression with distant metastasis-free survival (DMFS). mRNA expression of the key enzyme of cholesterol biosynthesis, squalene epoxidase (SQLE, chromosomal location 8q24.1), was associated with ER+ 7p+/8q+ breast cancer. Distant metastasis-free survival in stage I/II breast cancer cases was significantly inversely related to SQLE mRNA in multivariate Cox analysis (
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| doi_str_mv | 10.1038/sj.bjc.6604556 |
| format | article |
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P
<0.001) in two independent patient cohorts of 160 patients each. The clinically favourable group associated with a low SQLE mRNA expression could be further divided by mRNA expression levels of the oestrogen-regulated zinc transporter LIV-1. The data strongly support that SQLE mRNA expression might indicate high-risk ER+ stage I/II breast cancers. Further studies on tumour tissue from standardised treated patients, for example with tamoxifen, may validate the role of SQLE as a novel diagnostic parameter for ER+ early stage breast cancers.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/sj.bjc.6604556</identifier><identifier>PMID: 18728668</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Base Sequence ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - enzymology ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Cancer Research ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 8 ; Clinical outcomes ; DNA Primers ; DNA, Complementary ; Drug Resistance ; Epidemiology ; Gene expression ; Gene Expression Profiling ; Gynecology ; Gynecology. Andrology. Obstetrics ; Humans ; Mammary gland diseases ; Medical prognosis ; Medical research ; Medical sciences ; Metastasis ; Molecular Diagnostics ; Molecular Medicine ; Neoplasm Metastasis ; Obstetrics ; Oligonucleotide Array Sequence Analysis ; Oncology ; Patients ; Prognosis ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - genetics ; Squalene Monooxygenase - genetics ; Survival Analysis ; Treatment Outcome ; Tumors</subject><ispartof>British journal of cancer, 2008-09, Vol.99 (5), p.774-780</ispartof><rights>The Author(s) 2008</rights><rights>2008 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Sep 2, 2008</rights><rights>Copyright © 2008 Cancer Research UK 2008 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c569t-9acbfc852963a16181e3b27b914bc8e32c5d47a8cf28ae68a2ba0932b2a3c143</citedby><cites>FETCH-LOGICAL-c569t-9acbfc852963a16181e3b27b914bc8e32c5d47a8cf28ae68a2ba0932b2a3c143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528137/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528137/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20657567$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18728668$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Helms, M W</creatorcontrib><creatorcontrib>Kemming, D</creatorcontrib><creatorcontrib>Pospisil, H</creatorcontrib><creatorcontrib>Vogt, U</creatorcontrib><creatorcontrib>Buerger, H</creatorcontrib><creatorcontrib>Korsching, E</creatorcontrib><creatorcontrib>Liedtke, C</creatorcontrib><creatorcontrib>Schlotter, C M</creatorcontrib><creatorcontrib>Wang, A</creatorcontrib><creatorcontrib>Chan, S Y</creatorcontrib><creatorcontrib>Brandt, B H</creatorcontrib><title>Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional changes associated with this breast cancer subtype, we applied suppression subtractive hybridisation method to analyse differentially expressed genes among six breast tumours with and without chromosomal 7p and 8q gains. Identified mRNAs were validated by real-time RT–PCR in tissue samples obtained from 186 patients with stage I/II breast cancer. Advanced statistical methods were applied to identify associations of mRNA expression with distant metastasis-free survival (DMFS). mRNA expression of the key enzyme of cholesterol biosynthesis, squalene epoxidase (SQLE, chromosomal location 8q24.1), was associated with ER+ 7p+/8q+ breast cancer. Distant metastasis-free survival in stage I/II breast cancer cases was significantly inversely related to SQLE mRNA in multivariate Cox analysis (
P
<0.001) in two independent patient cohorts of 160 patients each. The clinically favourable group associated with a low SQLE mRNA expression could be further divided by mRNA expression levels of the oestrogen-regulated zinc transporter LIV-1. The data strongly support that SQLE mRNA expression might indicate high-risk ER+ stage I/II breast cancers. Further studies on tumour tissue from standardised treated patients, for example with tamoxifen, may validate the role of SQLE as a novel diagnostic parameter for ER+ early stage breast cancers.</description><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - enzymology</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer Research</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 8</subject><subject>Clinical outcomes</subject><subject>DNA Primers</subject><subject>DNA, Complementary</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gynecology</subject><subject>Gynecology. Andrology. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Helms, M W</au><au>Kemming, D</au><au>Pospisil, H</au><au>Vogt, U</au><au>Buerger, H</au><au>Korsching, E</au><au>Liedtke, C</au><au>Schlotter, C M</au><au>Wang, A</au><au>Chan, S Y</au><au>Brandt, B H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2008-09-02</date><risdate>2008</risdate><volume>99</volume><issue>5</issue><spage>774</spage><epage>780</epage><pages>774-780</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional changes associated with this breast cancer subtype, we applied suppression subtractive hybridisation method to analyse differentially expressed genes among six breast tumours with and without chromosomal 7p and 8q gains. Identified mRNAs were validated by real-time RT–PCR in tissue samples obtained from 186 patients with stage I/II breast cancer. Advanced statistical methods were applied to identify associations of mRNA expression with distant metastasis-free survival (DMFS). mRNA expression of the key enzyme of cholesterol biosynthesis, squalene epoxidase (SQLE, chromosomal location 8q24.1), was associated with ER+ 7p+/8q+ breast cancer. Distant metastasis-free survival in stage I/II breast cancer cases was significantly inversely related to SQLE mRNA in multivariate Cox analysis (
P
<0.001) in two independent patient cohorts of 160 patients each. The clinically favourable group associated with a low SQLE mRNA expression could be further divided by mRNA expression levels of the oestrogen-regulated zinc transporter LIV-1. The data strongly support that SQLE mRNA expression might indicate high-risk ER+ stage I/II breast cancers. Further studies on tumour tissue from standardised treated patients, for example with tamoxifen, may validate the role of SQLE as a novel diagnostic parameter for ER+ early stage breast cancers.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>18728668</pmid><doi>10.1038/sj.bjc.6604556</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of cancer, 2008-09, Vol.99 (5), p.774-780 |
| issn | 0007-0920 1532-1827 |
| language | eng |
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| source | PubMed Central |
| subjects | Base Sequence Biological and medical sciences Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - enzymology Breast Neoplasms - genetics Breast Neoplasms - pathology Cancer Research Chromosome Mapping Chromosomes Chromosomes, Human, Pair 8 Clinical outcomes DNA Primers DNA, Complementary Drug Resistance Epidemiology Gene expression Gene Expression Profiling Gynecology Gynecology. Andrology. Obstetrics Humans Mammary gland diseases Medical prognosis Medical research Medical sciences Metastasis Molecular Diagnostics Molecular Medicine Neoplasm Metastasis Obstetrics Oligonucleotide Array Sequence Analysis Oncology Patients Prognosis Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics Squalene Monooxygenase - genetics Survival Analysis Treatment Outcome Tumors |
| title | Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease |
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