Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B‐Cell Lymphoma
Purpose Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohist...
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creator | Suzuki, Masaki Muroi, Atsushi Nojima, Masanori Numata, Ayumi Takasaki, Hirotaka Sakai, Rika Yokose, Tomoyuki Miyagi, Yohei Koshikawa, Naohiko |
description | Purpose
Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse‐phase‐protein‐array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated.
Experimental design
The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki‐67, and C‐MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX‐5.
Results
The CD20‐adjusted data for CD5, MUM1, BCL2, Ki‐67, and C‐MYC has better correlation with IHC results than PAX‐5‐adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C‐MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882).
Conclusions and clinical relevance
Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis. |
doi_str_mv | 10.1002/prca.201900091 |
format | Article |
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Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse‐phase‐protein‐array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated.
Experimental design
The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki‐67, and C‐MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX‐5.
Results
The CD20‐adjusted data for CD5, MUM1, BCL2, Ki‐67, and C‐MYC has better correlation with IHC results than PAX‐5‐adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C‐MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882).
Conclusions and clinical relevance
Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis.</description><identifier>ISSN: 1862-8346</identifier><identifier>EISSN: 1862-8354</identifier><identifier>DOI: 10.1002/prca.201900091</identifier><identifier>PMID: 31721454</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Antigens, CD20 - genetics ; Arrays ; Bcl-6 protein ; Biomarkers ; Biomarkers, Tumor - genetics ; CD20 antigen ; CD5 antigen ; CD5 Antigens - genetics ; Correlation ; C‐MYC ; Design of experiments ; Diagnosis ; diffuse large B‐cell lymphoma (DLBCL) ; Experimental design ; Female ; Gene Expression Regulation, Neoplastic - genetics ; Humans ; Immunohistochemistry ; immunohistochemistry (IHC) ; Immunohistochemistry - methods ; Interferon Regulatory Factors - genetics ; Ki-67 Antigen - genetics ; Lymphoma ; lymphoma prognosis ; Lymphoma, Large B-Cell, Diffuse - diagnosis ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - pathology ; Lymphoma, Non-Hodgkin - diagnosis ; Lymphoma, Non-Hodgkin - genetics ; Lymphoma, Non-Hodgkin - pathology ; Male ; Middle Aged ; Myc protein ; Non-Hodgkin's lymphoma ; PAX5 Transcription Factor - genetics ; Prognosis ; Protein Array Analysis - methods ; Protein arrays ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - genetics ; Proto-Oncogene Proteins c-myc - genetics ; reverse‐phase‐protein‐array (RPPA)</subject><ispartof>Proteomics. Clinical applications, 2020-01, Vol.14 (1), p.e1900091-n/a</ispartof><rights>2019 The Authors. published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2019 The Authors. Proteomics - Clinical Application published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>2020 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5292-bf635139502d855146d86745ad7ab33fdbde20187160b660e25faa4b604f7fc3</citedby><cites>FETCH-LOGICAL-c5292-bf635139502d855146d86745ad7ab33fdbde20187160b660e25faa4b604f7fc3</cites><orcidid>0000-0002-4539-888X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fprca.201900091$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fprca.201900091$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31721454$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Masaki</creatorcontrib><creatorcontrib>Muroi, Atsushi</creatorcontrib><creatorcontrib>Nojima, Masanori</creatorcontrib><creatorcontrib>Numata, Ayumi</creatorcontrib><creatorcontrib>Takasaki, Hirotaka</creatorcontrib><creatorcontrib>Sakai, Rika</creatorcontrib><creatorcontrib>Yokose, Tomoyuki</creatorcontrib><creatorcontrib>Miyagi, Yohei</creatorcontrib><creatorcontrib>Koshikawa, Naohiko</creatorcontrib><title>Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B‐Cell Lymphoma</title><title>Proteomics. Clinical applications</title><addtitle>Proteomics Clin Appl</addtitle><description>Purpose
Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse‐phase‐protein‐array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated.
Experimental design
The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki‐67, and C‐MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX‐5.
Results
The CD20‐adjusted data for CD5, MUM1, BCL2, Ki‐67, and C‐MYC has better correlation with IHC results than PAX‐5‐adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C‐MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882).
Conclusions and clinical relevance
Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antigens, CD20 - genetics</subject><subject>Arrays</subject><subject>Bcl-6 protein</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>CD20 antigen</subject><subject>CD5 antigen</subject><subject>CD5 Antigens - genetics</subject><subject>Correlation</subject><subject>C‐MYC</subject><subject>Design of experiments</subject><subject>Diagnosis</subject><subject>diffuse large B‐cell lymphoma (DLBCL)</subject><subject>Experimental design</subject><subject>Female</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>immunohistochemistry (IHC)</subject><subject>Immunohistochemistry - methods</subject><subject>Interferon Regulatory Factors - genetics</subject><subject>Ki-67 Antigen - genetics</subject><subject>Lymphoma</subject><subject>lymphoma prognosis</subject><subject>Lymphoma, Large B-Cell, Diffuse - diagnosis</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - pathology</subject><subject>Lymphoma, Non-Hodgkin - diagnosis</subject><subject>Lymphoma, Non-Hodgkin - genetics</subject><subject>Lymphoma, Non-Hodgkin - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Myc protein</subject><subject>Non-Hodgkin's lymphoma</subject><subject>PAX5 Transcription Factor - genetics</subject><subject>Prognosis</subject><subject>Protein Array Analysis - methods</subject><subject>Protein arrays</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><subject>Proto-Oncogene Proteins c-myc - genetics</subject><subject>reverse‐phase‐protein‐array (RPPA)</subject><issn>1862-8346</issn><issn>1862-8354</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS1ERUthyxJZYsNmhuvfJBukYSgt0iCqqqwtJ7E7bj1xaieDsuMReEaeBI-mHQEbNr6W7nePztFB6BWBOQGg7_rY6DkFUgFARZ6gE1JKOiuZ4E8Pfy6P0fOUbgEEpwU8Q8eMFJRwwU_Q3bfBeTdMOFis8ZXZmpgMvlzr3RvDYFyHFzHqCQ8Bn221H_Vg8JfRD673Bn9wYaPjXT7CGfzorB3z4UrHm7z79ePn0niPV9OmX2fuBTqy2ifz8mGeoutPZ9fLi9nq6_nn5WI1awSt6Ky2kgnCKgG0LYUgXLalLLjQbaFrxmxbtyYnLgsioZYSDBVWa15L4LawDTtF7_ey_VhvTNuYbojaqz66bHVSQTv196Zza3UTtqoAYIUUWeDtg0AM96NJg9q41OQkujNhTIoywqnIBklG3_yD3oYxdjldppisGHCyo-Z7qokhpWjswQwBtatR7WpUhxrzwes_Ixzwx94ywPfAd-fN9B85dXm1XFAClP0GeImpjw</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Suzuki, Masaki</creator><creator>Muroi, Atsushi</creator><creator>Nojima, Masanori</creator><creator>Numata, Ayumi</creator><creator>Takasaki, Hirotaka</creator><creator>Sakai, Rika</creator><creator>Yokose, Tomoyuki</creator><creator>Miyagi, Yohei</creator><creator>Koshikawa, Naohiko</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-4539-888X</orcidid></search><sort><creationdate>202001</creationdate><title>Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B‐Cell Lymphoma</title><author>Suzuki, Masaki ; Muroi, Atsushi ; Nojima, Masanori ; Numata, Ayumi ; Takasaki, Hirotaka ; Sakai, Rika ; Yokose, Tomoyuki ; Miyagi, Yohei ; Koshikawa, Naohiko</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5292-bf635139502d855146d86745ad7ab33fdbde20187160b660e25faa4b604f7fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antigens, CD20 - genetics</topic><topic>Arrays</topic><topic>Bcl-6 protein</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>CD20 antigen</topic><topic>CD5 antigen</topic><topic>CD5 Antigens - genetics</topic><topic>Correlation</topic><topic>C‐MYC</topic><topic>Design of experiments</topic><topic>Diagnosis</topic><topic>diffuse large B‐cell lymphoma (DLBCL)</topic><topic>Experimental design</topic><topic>Female</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>immunohistochemistry (IHC)</topic><topic>Immunohistochemistry - methods</topic><topic>Interferon Regulatory Factors - genetics</topic><topic>Ki-67 Antigen - genetics</topic><topic>Lymphoma</topic><topic>lymphoma prognosis</topic><topic>Lymphoma, Large B-Cell, Diffuse - diagnosis</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - pathology</topic><topic>Lymphoma, Non-Hodgkin - diagnosis</topic><topic>Lymphoma, Non-Hodgkin - genetics</topic><topic>Lymphoma, Non-Hodgkin - pathology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Myc protein</topic><topic>Non-Hodgkin's lymphoma</topic><topic>PAX5 Transcription Factor - genetics</topic><topic>Prognosis</topic><topic>Protein Array Analysis - methods</topic><topic>Protein arrays</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - genetics</topic><topic>Proto-Oncogene Proteins c-myc - genetics</topic><topic>reverse‐phase‐protein‐array (RPPA)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suzuki, Masaki</creatorcontrib><creatorcontrib>Muroi, Atsushi</creatorcontrib><creatorcontrib>Nojima, Masanori</creatorcontrib><creatorcontrib>Numata, Ayumi</creatorcontrib><creatorcontrib>Takasaki, Hirotaka</creatorcontrib><creatorcontrib>Sakai, Rika</creatorcontrib><creatorcontrib>Yokose, Tomoyuki</creatorcontrib><creatorcontrib>Miyagi, Yohei</creatorcontrib><creatorcontrib>Koshikawa, Naohiko</creatorcontrib><collection>Wiley Online Library (Open Access Collection)</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proteomics. Clinical applications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Masaki</au><au>Muroi, Atsushi</au><au>Nojima, Masanori</au><au>Numata, Ayumi</au><au>Takasaki, Hirotaka</au><au>Sakai, Rika</au><au>Yokose, Tomoyuki</au><au>Miyagi, Yohei</au><au>Koshikawa, Naohiko</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B‐Cell Lymphoma</atitle><jtitle>Proteomics. Clinical applications</jtitle><addtitle>Proteomics Clin Appl</addtitle><date>2020-01</date><risdate>2020</risdate><volume>14</volume><issue>1</issue><spage>e1900091</spage><epage>n/a</epage><pages>e1900091-n/a</pages><issn>1862-8346</issn><eissn>1862-8354</eissn><abstract>Purpose
Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse‐phase‐protein‐array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated.
Experimental design
The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki‐67, and C‐MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX‐5.
Results
The CD20‐adjusted data for CD5, MUM1, BCL2, Ki‐67, and C‐MYC has better correlation with IHC results than PAX‐5‐adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C‐MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882).
Conclusions and clinical relevance
Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31721454</pmid><doi>10.1002/prca.201900091</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4539-888X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adult Aged Aged, 80 and over Antigens, CD20 - genetics Arrays Bcl-6 protein Biomarkers Biomarkers, Tumor - genetics CD20 antigen CD5 antigen CD5 Antigens - genetics Correlation C‐MYC Design of experiments Diagnosis diffuse large B‐cell lymphoma (DLBCL) Experimental design Female Gene Expression Regulation, Neoplastic - genetics Humans Immunohistochemistry immunohistochemistry (IHC) Immunohistochemistry - methods Interferon Regulatory Factors - genetics Ki-67 Antigen - genetics Lymphoma lymphoma prognosis Lymphoma, Large B-Cell, Diffuse - diagnosis Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - pathology Lymphoma, Non-Hodgkin - diagnosis Lymphoma, Non-Hodgkin - genetics Lymphoma, Non-Hodgkin - pathology Male Middle Aged Myc protein Non-Hodgkin's lymphoma PAX5 Transcription Factor - genetics Prognosis Protein Array Analysis - methods Protein arrays Proteins Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-myc - genetics reverse‐phase‐protein‐array (RPPA) |
title | Utility of a Reverse Phase Protein Array to Evaluate Multiple Biomarkers in Diffuse Large B‐Cell Lymphoma |
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