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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Veröffentlicht in:Proteomics. Clinical applications 2020-01, Vol.14 (1), p.e1900091-n/a
Hauptverfasser: Suzuki, Masaki, Muroi, Atsushi, Nojima, Masanori, Numata, Ayumi, Takasaki, Hirotaka, Sakai, Rika, Yokose, Tomoyuki, Miyagi, Yohei, Koshikawa, Naohiko
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container_start_page e1900091
container_title Proteomics. Clinical applications
container_volume 14
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
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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 &gt;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 &amp; Co. KGaA, Weinheim</rights><rights>2019 The Authors. Proteomics - Clinical Application published by WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.</rights><rights>2020 WILEY‐VCH Verlag GmbH &amp; 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 &gt;0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882). 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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 &gt;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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