Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer
Background: APC mutations ( APC -mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear. Methods: APC prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to...
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| Veröffentlicht in: | British journal of cancer 2015-09, Vol.113 (6), p.979-988 |
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| creator | Jorissen, Robert N Christie, Michael Mouradov, Dmitri Sakthianandeswaren, Anuratha Li, Shan Love, Christopher Xu, Zheng-Zhou Molloy, Peter L Jones, Ian T McLaughlin, Stephen Ward, Robyn L Hawkins, Nicholas J Ruszkiewicz, Andrew R Moore, James Burgess, Antony W Busam, Dana Zhao, Qi Strausberg, Robert L Lipton, Lara Desai, Jayesh Gibbs, Peter Sieber, Oliver M |
| description | Background:
APC
mutations (
APC
-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.
Methods:
APC
prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify
APC
mutation status, and classifier ability to predict prognosis was examined in an independent cohort.
Results:
Wild-type
APC
microsatellite stable (
APC
-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than
APC
-mt/MSS proximal,
APC
-wt/MSS distal and
APC
-mt/MSS distal tumours (OS HR⩾1.79,
P
⩽0.015; RFS HR⩾1.88,
P
⩽0.026).
APC
was a stronger prognostic indicator than
BRAF
,
KRAS
,
PIK3CA
,
TP53
, CpG island methylator phenotype or chromosomal instability status (
P
⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an
APC
-wt-like signature (
P
=0.019).
APC
status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer,
APC
-wt-like signature MSS cases showed poorer survival than
APC
-mt-like signature MSS or MSI cases (OS HR⩾2.50,
P
⩽0.010; RFS HR⩾2.14,
P
⩽0.025). Poor prognosis
APC
-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (
P
⩽0.016).
Conclusions:
APC
-wt status is a marker of poor prognosis in MSS proximal colon cancer. |
| doi_str_mv | 10.1038/bjc.2015.296 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4578087</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3951584091</sourcerecordid><originalsourceid>FETCH-LOGICAL-c586t-7fa047389ca0e4d23d5b4bc326897a26706137f4de0e01b019ddc0ccd1b78fa63</originalsourceid><addsrcrecordid>eNptkc1rGzEQxUVpqJ20t5zLQi89ZJ2RtCtpL4Fgmg8wJIeUHoVW0joya2kjrUvz30fGiXFDTsMwP97Mm4fQKYYZBirO25WeEcD1jDTsE5rimpISC8I_oykA8BIaAhN0nNIqtw0I_gVNCKNQC1ZN0cMf15tyfB5scXk_L4ZojdNjKoYQYu7C0ofkUuF8sXY6hqRG2_dutGUaVdvbLfLPrVVf6NAHX2jltY1f0VGn-mS_vdYT9Pvq18P8plzcXd_OLxelzsvHkncKKk5FoxXYyhBq6rZqNSVMNFwRxoFhyrvKWLCAW8CNMRq0NrjlolOMnqCLne6wadfWaOvHqHo5xHxRfJZBOfn_xLtHuQx_ZVVzkT-RBX6-CsTwtLFplGuXdHaovA2bJDHHtCYCE5HRH-_QVdhEn-1lilWCN5g1mTrbUdtfpWi7_TEY5DYumeOS27hkjivj3w8N7OG3fDJQ7oCUR35p48HWjwRfAMBYoJM</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1764879169</pqid></control><display><type>article</type><title>Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer</title><source>MEDLINE</source><source>Springer Online Journals</source><source>Nature</source><source>PubMed Central</source><source>EZB Electronic Journals Library</source><creator>Jorissen, Robert N ; Christie, Michael ; Mouradov, Dmitri ; Sakthianandeswaren, Anuratha ; Li, Shan ; Love, Christopher ; Xu, Zheng-Zhou ; Molloy, Peter L ; Jones, Ian T ; McLaughlin, Stephen ; Ward, Robyn L ; Hawkins, Nicholas J ; Ruszkiewicz, Andrew R ; Moore, James ; Burgess, Antony W ; Busam, Dana ; Zhao, Qi ; Strausberg, Robert L ; Lipton, Lara ; Desai, Jayesh ; Gibbs, Peter ; Sieber, Oliver M</creator><creatorcontrib>Jorissen, Robert N ; Christie, Michael ; Mouradov, Dmitri ; Sakthianandeswaren, Anuratha ; Li, Shan ; Love, Christopher ; Xu, Zheng-Zhou ; Molloy, Peter L ; Jones, Ian T ; McLaughlin, Stephen ; Ward, Robyn L ; Hawkins, Nicholas J ; Ruszkiewicz, Andrew R ; Moore, James ; Burgess, Antony W ; Busam, Dana ; Zhao, Qi ; Strausberg, Robert L ; Lipton, Lara ; Desai, Jayesh ; Gibbs, Peter ; Sieber, Oliver M</creatorcontrib><description>Background:
APC
mutations (
APC
-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.
Methods:
APC
prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify
APC
mutation status, and classifier ability to predict prognosis was examined in an independent cohort.
Results:
Wild-type
APC
microsatellite stable (
APC
-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than
APC
-mt/MSS proximal,
APC
-wt/MSS distal and
APC
-mt/MSS distal tumours (OS HR⩾1.79,
P
⩽0.015; RFS HR⩾1.88,
P
⩽0.026).
APC
was a stronger prognostic indicator than
BRAF
,
KRAS
,
PIK3CA
,
TP53
, CpG island methylator phenotype or chromosomal instability status (
P
⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an
APC
-wt-like signature (
P
=0.019).
APC
status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer,
APC
-wt-like signature MSS cases showed poorer survival than
APC
-mt-like signature MSS or MSI cases (OS HR⩾2.50,
P
⩽0.010; RFS HR⩾2.14,
P
⩽0.025). Poor prognosis
APC
-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (
P
⩽0.016).
Conclusions:
APC
-wt status is a marker of poor prognosis in MSS proximal colon cancer.</description><identifier>ISSN: 0007-0920</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/bjc.2015.296</identifier><identifier>PMID: 26305864</identifier><identifier>CODEN: BJCAAI</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/53/2422 ; 692/699/1503/1581/1392/1885 ; 692/699/67/68 ; 692/700/1750 ; Adenomatous Polyposis Coli Protein - genetics ; Adult ; Aged ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Class I Phosphatidylinositol 3-Kinases ; Colonic Neoplasms - genetics ; Colonic Neoplasms - mortality ; Colonic Neoplasms - pathology ; CpG Islands ; Disease-Free Survival ; Drug Resistance ; Epidemiology ; Female ; Genes, p53 ; Genes, ras ; Genetics & Genomics ; genetics-and-genomics ; Humans ; Male ; Microsatellite Instability ; Microsatellite Repeats - genetics ; Middle Aged ; Molecular Medicine ; Neoplasm Recurrence, Local - genetics ; Neoplasm Recurrence, Local - mortality ; Oncology ; Phosphatidylinositol 3-Kinases - genetics ; Prognosis ; Protein Array Analysis ; Proto-Oncogene Proteins B-raf - genetics</subject><ispartof>British journal of cancer, 2015-09, Vol.113 (6), p.979-988</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Sep 15, 2015</rights><rights>Copyright © 2015 Cancer Research UK 2015 Cancer Research UK</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c586t-7fa047389ca0e4d23d5b4bc326897a26706137f4de0e01b019ddc0ccd1b78fa63</citedby><cites>FETCH-LOGICAL-c586t-7fa047389ca0e4d23d5b4bc326897a26706137f4de0e01b019ddc0ccd1b78fa63</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/PMC4578087/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578087/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,41464,42533,51294,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26305864$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jorissen, Robert N</creatorcontrib><creatorcontrib>Christie, Michael</creatorcontrib><creatorcontrib>Mouradov, Dmitri</creatorcontrib><creatorcontrib>Sakthianandeswaren, Anuratha</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Love, Christopher</creatorcontrib><creatorcontrib>Xu, Zheng-Zhou</creatorcontrib><creatorcontrib>Molloy, Peter L</creatorcontrib><creatorcontrib>Jones, Ian T</creatorcontrib><creatorcontrib>McLaughlin, Stephen</creatorcontrib><creatorcontrib>Ward, Robyn L</creatorcontrib><creatorcontrib>Hawkins, Nicholas J</creatorcontrib><creatorcontrib>Ruszkiewicz, Andrew R</creatorcontrib><creatorcontrib>Moore, James</creatorcontrib><creatorcontrib>Burgess, Antony W</creatorcontrib><creatorcontrib>Busam, Dana</creatorcontrib><creatorcontrib>Zhao, Qi</creatorcontrib><creatorcontrib>Strausberg, Robert L</creatorcontrib><creatorcontrib>Lipton, Lara</creatorcontrib><creatorcontrib>Desai, Jayesh</creatorcontrib><creatorcontrib>Gibbs, Peter</creatorcontrib><creatorcontrib>Sieber, Oliver M</creatorcontrib><title>Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background:
APC
mutations (
APC
-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.
Methods:
APC
prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify
APC
mutation status, and classifier ability to predict prognosis was examined in an independent cohort.
Results:
Wild-type
APC
microsatellite stable (
APC
-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than
APC
-mt/MSS proximal,
APC
-wt/MSS distal and
APC
-mt/MSS distal tumours (OS HR⩾1.79,
P
⩽0.015; RFS HR⩾1.88,
P
⩽0.026).
APC
was a stronger prognostic indicator than
BRAF
,
KRAS
,
PIK3CA
,
TP53
, CpG island methylator phenotype or chromosomal instability status (
P
⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an
APC
-wt-like signature (
P
=0.019).
APC
status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer,
APC
-wt-like signature MSS cases showed poorer survival than
APC
-mt-like signature MSS or MSI cases (OS HR⩾2.50,
P
⩽0.010; RFS HR⩾2.14,
P
⩽0.025). Poor prognosis
APC
-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (
P
⩽0.016).
Conclusions:
APC
-wt status is a marker of poor prognosis in MSS proximal colon cancer.</description><subject>692/53/2422</subject><subject>692/699/1503/1581/1392/1885</subject><subject>692/699/67/68</subject><subject>692/700/1750</subject><subject>Adenomatous Polyposis Coli Protein - genetics</subject><subject>Adult</subject><subject>Aged</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Class I Phosphatidylinositol 3-Kinases</subject><subject>Colonic Neoplasms - genetics</subject><subject>Colonic Neoplasms - mortality</subject><subject>Colonic Neoplasms - pathology</subject><subject>CpG Islands</subject><subject>Disease-Free Survival</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Genes, p53</subject><subject>Genes, ras</subject><subject>Genetics & Genomics</subject><subject>genetics-and-genomics</subject><subject>Humans</subject><subject>Male</subject><subject>Microsatellite Instability</subject><subject>Microsatellite Repeats - genetics</subject><subject>Middle Aged</subject><subject>Molecular Medicine</subject><subject>Neoplasm Recurrence, Local - genetics</subject><subject>Neoplasm Recurrence, Local - mortality</subject><subject>Oncology</subject><subject>Phosphatidylinositol 3-Kinases - genetics</subject><subject>Prognosis</subject><subject>Protein Array Analysis</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><issn>0007-0920</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkc1rGzEQxUVpqJ20t5zLQi89ZJ2RtCtpL4Fgmg8wJIeUHoVW0joya2kjrUvz30fGiXFDTsMwP97Mm4fQKYYZBirO25WeEcD1jDTsE5rimpISC8I_oykA8BIaAhN0nNIqtw0I_gVNCKNQC1ZN0cMf15tyfB5scXk_L4ZojdNjKoYQYu7C0ofkUuF8sXY6hqRG2_dutGUaVdvbLfLPrVVf6NAHX2jltY1f0VGn-mS_vdYT9Pvq18P8plzcXd_OLxelzsvHkncKKk5FoxXYyhBq6rZqNSVMNFwRxoFhyrvKWLCAW8CNMRq0NrjlolOMnqCLne6wadfWaOvHqHo5xHxRfJZBOfn_xLtHuQx_ZVVzkT-RBX6-CsTwtLFplGuXdHaovA2bJDHHtCYCE5HRH-_QVdhEn-1lilWCN5g1mTrbUdtfpWi7_TEY5DYumeOS27hkjivj3w8N7OG3fDJQ7oCUR35p48HWjwRfAMBYoJM</recordid><startdate>20150915</startdate><enddate>20150915</enddate><creator>Jorissen, Robert N</creator><creator>Christie, Michael</creator><creator>Mouradov, Dmitri</creator><creator>Sakthianandeswaren, Anuratha</creator><creator>Li, Shan</creator><creator>Love, Christopher</creator><creator>Xu, Zheng-Zhou</creator><creator>Molloy, Peter L</creator><creator>Jones, Ian T</creator><creator>McLaughlin, Stephen</creator><creator>Ward, Robyn L</creator><creator>Hawkins, Nicholas J</creator><creator>Ruszkiewicz, Andrew R</creator><creator>Moore, James</creator><creator>Burgess, Antony W</creator><creator>Busam, Dana</creator><creator>Zhao, Qi</creator><creator>Strausberg, Robert L</creator><creator>Lipton, Lara</creator><creator>Desai, Jayesh</creator><creator>Gibbs, Peter</creator><creator>Sieber, Oliver M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150915</creationdate><title>Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer</title><author>Jorissen, Robert N ; Christie, Michael ; Mouradov, Dmitri ; Sakthianandeswaren, Anuratha ; Li, Shan ; Love, Christopher ; Xu, Zheng-Zhou ; Molloy, Peter L ; Jones, Ian T ; McLaughlin, Stephen ; Ward, Robyn L ; Hawkins, Nicholas J ; Ruszkiewicz, Andrew R ; Moore, James ; Burgess, Antony W ; Busam, Dana ; Zhao, Qi ; Strausberg, Robert L ; Lipton, Lara ; Desai, Jayesh ; Gibbs, Peter ; Sieber, Oliver M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c586t-7fa047389ca0e4d23d5b4bc326897a26706137f4de0e01b019ddc0ccd1b78fa63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>692/53/2422</topic><topic>692/699/1503/1581/1392/1885</topic><topic>692/699/67/68</topic><topic>692/700/1750</topic><topic>Adenomatous Polyposis Coli Protein - genetics</topic><topic>Adult</topic><topic>Aged</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Class I Phosphatidylinositol 3-Kinases</topic><topic>Colonic Neoplasms - genetics</topic><topic>Colonic Neoplasms - mortality</topic><topic>Colonic Neoplasms - pathology</topic><topic>CpG Islands</topic><topic>Disease-Free Survival</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Genes, p53</topic><topic>Genes, ras</topic><topic>Genetics & Genomics</topic><topic>genetics-and-genomics</topic><topic>Humans</topic><topic>Male</topic><topic>Microsatellite Instability</topic><topic>Microsatellite Repeats - genetics</topic><topic>Middle Aged</topic><topic>Molecular Medicine</topic><topic>Neoplasm Recurrence, Local - genetics</topic><topic>Neoplasm Recurrence, Local - mortality</topic><topic>Oncology</topic><topic>Phosphatidylinositol 3-Kinases - genetics</topic><topic>Prognosis</topic><topic>Protein Array Analysis</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jorissen, Robert N</creatorcontrib><creatorcontrib>Christie, Michael</creatorcontrib><creatorcontrib>Mouradov, Dmitri</creatorcontrib><creatorcontrib>Sakthianandeswaren, Anuratha</creatorcontrib><creatorcontrib>Li, Shan</creatorcontrib><creatorcontrib>Love, Christopher</creatorcontrib><creatorcontrib>Xu, Zheng-Zhou</creatorcontrib><creatorcontrib>Molloy, Peter L</creatorcontrib><creatorcontrib>Jones, Ian T</creatorcontrib><creatorcontrib>McLaughlin, Stephen</creatorcontrib><creatorcontrib>Ward, Robyn L</creatorcontrib><creatorcontrib>Hawkins, Nicholas J</creatorcontrib><creatorcontrib>Ruszkiewicz, Andrew R</creatorcontrib><creatorcontrib>Moore, James</creatorcontrib><creatorcontrib>Burgess, Antony W</creatorcontrib><creatorcontrib>Busam, Dana</creatorcontrib><creatorcontrib>Zhao, Qi</creatorcontrib><creatorcontrib>Strausberg, Robert L</creatorcontrib><creatorcontrib>Lipton, Lara</creatorcontrib><creatorcontrib>Desai, Jayesh</creatorcontrib><creatorcontrib>Gibbs, Peter</creatorcontrib><creatorcontrib>Sieber, Oliver M</creatorcontrib><collection>SpringerOpen</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>Nursing & Allied Health Database (ProQuest)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection (Proquest)</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database (Proquest)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - 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>Jorissen, Robert N</au><au>Christie, Michael</au><au>Mouradov, Dmitri</au><au>Sakthianandeswaren, Anuratha</au><au>Li, Shan</au><au>Love, Christopher</au><au>Xu, Zheng-Zhou</au><au>Molloy, Peter L</au><au>Jones, Ian T</au><au>McLaughlin, Stephen</au><au>Ward, Robyn L</au><au>Hawkins, Nicholas J</au><au>Ruszkiewicz, Andrew R</au><au>Moore, James</au><au>Burgess, Antony W</au><au>Busam, Dana</au><au>Zhao, Qi</au><au>Strausberg, Robert L</au><au>Lipton, Lara</au><au>Desai, Jayesh</au><au>Gibbs, Peter</au><au>Sieber, Oliver M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2015-09-15</date><risdate>2015</risdate><volume>113</volume><issue>6</issue><spage>979</spage><epage>988</epage><pages>979-988</pages><issn>0007-0920</issn><eissn>1532-1827</eissn><coden>BJCAAI</coden><abstract>Background:
APC
mutations (
APC
-mt) occur in ∼70% of colorectal cancers (CRCs), but their relationship to prognosis is unclear.
Methods:
APC
prognostic value was evaluated in 746 stage I–IV CRC patients, stratifying for tumour location and microsatellite instability (MSI). Microarrays were used to identify a gene signature that could classify
APC
mutation status, and classifier ability to predict prognosis was examined in an independent cohort.
Results:
Wild-type
APC
microsatellite stable (
APC
-wt/MSS) tumours from the proximal colon showed poorer overall and recurrence-free survival (OS, RFS) than
APC
-mt/MSS proximal,
APC
-wt/MSS distal and
APC
-mt/MSS distal tumours (OS HR⩾1.79,
P
⩽0.015; RFS HR⩾1.88,
P
⩽0.026).
APC
was a stronger prognostic indicator than
BRAF
,
KRAS
,
PIK3CA
,
TP53
, CpG island methylator phenotype or chromosomal instability status (
P
⩽0.036). Microarray analysis similarly revealed poorer survival in MSS proximal cancers with an
APC
-wt-like signature (
P
=0.019).
APC
status did not affect outcomes in MSI tumours. In a validation on 206 patients with proximal colon cancer,
APC
-wt-like signature MSS cases showed poorer survival than
APC
-mt-like signature MSS or MSI cases (OS HR⩾2.50,
P
⩽0.010; RFS HR⩾2.14,
P
⩽0.025). Poor prognosis
APC
-wt/MSS proximal tumours exhibited features of the sessile serrated neoplasia pathway (
P
⩽0.016).
Conclusions:
APC
-wt status is a marker of poor prognosis in MSS proximal colon cancer.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26305864</pmid><doi>10.1038/bjc.2015.296</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2015-09, Vol.113 (6), p.979-988 |
| issn | 0007-0920 1532-1827 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4578087 |
| source | MEDLINE; Springer Online Journals; Nature; PubMed Central; EZB Electronic Journals Library |
| subjects | 692/53/2422 692/699/1503/1581/1392/1885 692/699/67/68 692/700/1750 Adenomatous Polyposis Coli Protein - genetics Adult Aged Biomedical and Life Sciences Biomedicine Cancer Research Class I Phosphatidylinositol 3-Kinases Colonic Neoplasms - genetics Colonic Neoplasms - mortality Colonic Neoplasms - pathology CpG Islands Disease-Free Survival Drug Resistance Epidemiology Female Genes, p53 Genes, ras Genetics & Genomics genetics-and-genomics Humans Male Microsatellite Instability Microsatellite Repeats - genetics Middle Aged Molecular Medicine Neoplasm Recurrence, Local - genetics Neoplasm Recurrence, Local - mortality Oncology Phosphatidylinositol 3-Kinases - genetics Prognosis Protein Array Analysis Proto-Oncogene Proteins B-raf - genetics |
| title | Wild-type APC predicts poor prognosis in microsatellite-stable proximal colon cancer |
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