Intra-Tumoral Heterogeneity of HER2, FGFR2, cMET and ATM in Gastric Cancer: Optimizing Personalized Healthcare through Innovative Pathological and Statistical Analysis
Current drug development efforts on gastric cancer are directed against several molecular targets driving the growth of this neoplasm. Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profil...
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| description | Current drug development efforts on gastric cancer are directed against several molecular targets driving the growth of this neoplasm. Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods. |
| doi_str_mv | 10.1371/journal.pone.0143207 |
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Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0143207</identifier><identifier>PMID: 26587992</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Angiogenesis ; Ataxia ; Ataxia Telangiectasia Mutated Proteins - genetics ; Biomarkers ; Biomarkers, Tumor - genetics ; Biopsy ; Breast cancer ; Cancer ; Cancer therapies ; Cell cycle ; Clinical trials ; Deoxyribonucleic acid ; DNA ; Drug development ; ErbB-2 protein ; False Negative Reactions ; Fibroblast growth factor receptor 2 ; Gastric cancer ; Gene Amplification ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Growth factors ; Health care ; Heterogeneity ; Hospitals ; Humans ; Immunohistochemistry ; In Situ Hybridization, Fluorescence ; Kinases ; Medical innovations ; Medical prognosis ; Metastasis ; Neoplasia ; Ovarian cancer ; Patients ; Precision Medicine - methods ; Proteins ; Proto-Oncogene Proteins c-met - genetics ; R&D ; Receptor, ErbB-2 - genetics ; Receptor, Fibroblast Growth Factor, Type 2 - genetics ; Research & development ; Risk Assessment ; Statistical analysis ; Statistical methods ; Statistics ; Stomach cancer ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach Neoplasms - therapy ; Tumorigenesis ; Tumors</subject><ispartof>PloS one, 2015-11, Vol.10 (11), p.e0143207-e0143207</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Ye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Ye et al 2015 Ye et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-43d70b99da9be162de437b1a8812486910f881e0e7fd28bd88b4fd9f1d0fc0843</citedby><cites>FETCH-LOGICAL-c758t-43d70b99da9be162de437b1a8812486910f881e0e7fd28bd88b4fd9f1d0fc0843</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/PMC4654477/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654477/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26587992$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Peng</creatorcontrib><creatorcontrib>Zhang, Meizhuo</creatorcontrib><creatorcontrib>Fan, Shuqiong</creatorcontrib><creatorcontrib>Zhang, Tianwei</creatorcontrib><creatorcontrib>Fu, Haihua</creatorcontrib><creatorcontrib>Su, Xinying</creatorcontrib><creatorcontrib>Gavine, Paul R</creatorcontrib><creatorcontrib>Liu, Qiang</creatorcontrib><creatorcontrib>Yin, Xiaolu</creatorcontrib><title>Intra-Tumoral Heterogeneity of HER2, FGFR2, cMET and ATM in Gastric Cancer: Optimizing Personalized Healthcare through Innovative Pathological and Statistical Analysis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Current drug development efforts on gastric cancer are directed against several molecular targets driving the growth of this neoplasm. Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods.</description><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Ataxia</subject><subject>Ataxia Telangiectasia Mutated Proteins - genetics</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Clinical trials</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>Drug development</subject><subject>ErbB-2 protein</subject><subject>False Negative Reactions</subject><subject>Fibroblast growth factor receptor 2</subject><subject>Gastric cancer</subject><subject>Gene Amplification</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Growth factors</subject><subject>Health care</subject><subject>Heterogeneity</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>In Situ Hybridization, Fluorescence</subject><subject>Kinases</subject><subject>Medical innovations</subject><subject>Medical prognosis</subject><subject>Metastasis</subject><subject>Neoplasia</subject><subject>Ovarian cancer</subject><subject>Patients</subject><subject>Precision Medicine - methods</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-met - genetics</subject><subject>R&D</subject><subject>Receptor, ErbB-2 - genetics</subject><subject>Receptor, Fibroblast Growth Factor, Type 2 - genetics</subject><subject>Research & development</subject><subject>Risk Assessment</subject><subject>Statistical analysis</subject><subject>Statistical methods</subject><subject>Statistics</subject><subject>Stomach cancer</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - therapy</subject><subject>Tumorigenesis</subject><subject>Tumors</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk91qFDEUxwdRbK2-gWhAEAV3TTKZzIwXwrK03YWWlnb1NmTyMZsym6xJpti-kK9pZrstXemF5CLJye_8c85JTpa9RXCM8hJ9vXK9t7wbr51VY4hIjmH5LNtHdY5HFMP8-aP1XvYqhCsIi7yi9GW2h2lRlXWN97M_cxs9Hy36lfO8AzMVlXetssrEG-A0mB1e4C_g6PhomMTp4QJwK8FkcQqMBcc8RG8EmHIrlP8GztbRrMytsS04Vz64FJ65VTKp8i4uBfcKxKV3fbsEc2vdNY_mWoFzHpeuc60RKYBB_TKmgxA3-0nSuAkmvM5eaN4F9WY7H2Q_jg4X09no5Ox4Pp2cjERZVHFEclnCpq4lrxuFKJaK5GWDeFUhTCpaI6jTUkFVaomrRlZVQ7SsNZJQC1iR_CB7f6e77lxg2xoHhsq8gBDjYiDmd4R0_IqtvVlxf8McN2xjcL5l3KfgO8UohagsJC0aUhBVEa5hqXAteI1yqbFOWt-3t_XNSkmhhsfodkR3T6xZstZdM0ILQsoyCXzaCnj3q1chspUJQnUdt8r1m7gpQUWRD-iHf9Cns9tSLU8JGKtdulcMomxC8gJjgihN1PgJKg2pVkakD6lNsu84fN5xSExUv2PL-xDY_PLi_9mzn7vsx0fscvPPguv6aJwNuyC5A4V3IXilH4qMIBv66b4abOgntu2n5Pbu8QM9ON03UP4XzRcbCQ</recordid><startdate>20151120</startdate><enddate>20151120</enddate><creator>Ye, Peng</creator><creator>Zhang, Meizhuo</creator><creator>Fan, Shuqiong</creator><creator>Zhang, Tianwei</creator><creator>Fu, Haihua</creator><creator>Su, Xinying</creator><creator>Gavine, Paul R</creator><creator>Liu, Qiang</creator><creator>Yin, Xiaolu</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20151120</creationdate><title>Intra-Tumoral Heterogeneity of HER2, FGFR2, cMET and ATM in Gastric Cancer: Optimizing Personalized Healthcare through Innovative Pathological and Statistical Analysis</title><author>Ye, Peng ; Zhang, Meizhuo ; Fan, Shuqiong ; Zhang, Tianwei ; Fu, Haihua ; Su, Xinying ; Gavine, Paul R ; Liu, Qiang ; Yin, Xiaolu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-43d70b99da9be162de437b1a8812486910f881e0e7fd28bd88b4fd9f1d0fc0843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Analysis</topic><topic>Angiogenesis</topic><topic>Ataxia</topic><topic>Ataxia Telangiectasia Mutated Proteins - genetics</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biopsy</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Clinical trials</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>Drug development</topic><topic>ErbB-2 protein</topic><topic>False Negative Reactions</topic><topic>Fibroblast growth factor receptor 2</topic><topic>Gastric cancer</topic><topic>Gene Amplification</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Growth factors</topic><topic>Health care</topic><topic>Heterogeneity</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>In Situ Hybridization, Fluorescence</topic><topic>Kinases</topic><topic>Medical innovations</topic><topic>Medical prognosis</topic><topic>Metastasis</topic><topic>Neoplasia</topic><topic>Ovarian cancer</topic><topic>Patients</topic><topic>Precision Medicine - 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Intra-tumoral biomarker heterogeneity however, commonly observed in gastric cancer, could lead to biased selection of patients. MET, ATM, FGFR2, and HER2 were profiled on gastric cancer biopsy samples. An innovative pathological assessment was performed through scoring of individual biopsies against whole biopsies from a single patient to enable heterogeneity evaluation. Following this, false negative risks for each biomarker were estimated in silico. 166 gastric cancer cases with multiple biopsies from single patients were collected from Shanghai Renji Hospital. Following pre-set criteria, 56 ~ 78% cases showed low, 15 ~ 35% showed medium and 0 ~ 11% showed high heterogeneity within the biomarkers profiled. If 3 biopsies were collected from a single patient, the false negative risk for detection of the biomarkers was close to 5% (exception for FGFR2: 12.2%). When 6 biopsies were collected, the false negative risk approached 0%. Our study demonstrates the benefit of multiple biopsy sampling when considering personalized healthcare biomarker strategy, and provides an example to address the challenge of intra-tumoral biomarker heterogeneity using alternative pathological assessment and statistical methods.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26587992</pmid><doi>10.1371/journal.pone.0143207</doi><tpages>e0143207</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2015-11, Vol.10 (11), p.e0143207-e0143207 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1735002254 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Analysis Angiogenesis Ataxia Ataxia Telangiectasia Mutated Proteins - genetics Biomarkers Biomarkers, Tumor - genetics Biopsy Breast cancer Cancer Cancer therapies Cell cycle Clinical trials Deoxyribonucleic acid DNA Drug development ErbB-2 protein False Negative Reactions Fibroblast growth factor receptor 2 Gastric cancer Gene Amplification Gene Expression Profiling Gene Expression Regulation, Neoplastic Growth factors Health care Heterogeneity Hospitals Humans Immunohistochemistry In Situ Hybridization, Fluorescence Kinases Medical innovations Medical prognosis Metastasis Neoplasia Ovarian cancer Patients Precision Medicine - methods Proteins Proto-Oncogene Proteins c-met - genetics R&D Receptor, ErbB-2 - genetics Receptor, Fibroblast Growth Factor, Type 2 - genetics Research & development Risk Assessment Statistical analysis Statistical methods Statistics Stomach cancer Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach Neoplasms - therapy Tumorigenesis Tumors |
| title | Intra-Tumoral Heterogeneity of HER2, FGFR2, cMET and ATM in Gastric Cancer: Optimizing Personalized Healthcare through Innovative Pathological and Statistical Analysis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T04%3A31%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Intra-Tumoral%20Heterogeneity%20of%20HER2,%20FGFR2,%20cMET%20and%20ATM%20in%20Gastric%20Cancer:%20Optimizing%20Personalized%20Healthcare%20through%20Innovative%20Pathological%20and%20Statistical%20Analysis&rft.jtitle=PloS%20one&rft.au=Ye,%20Peng&rft.date=2015-11-20&rft.volume=10&rft.issue=11&rft.spage=e0143207&rft.epage=e0143207&rft.pages=e0143207-e0143207&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0143207&rft_dat=%3Cgale_plos_%3EA435224166%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1735002254&rft_id=info:pmid/26587992&rft_galeid=A435224166&rft_doaj_id=oai_doaj_org_article_660175d65b454e84af07e29ca913df2f&rfr_iscdi=true |