Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients
Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumo...
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| Veröffentlicht in: | Human cell : official journal of Human Cell Research Society 2023-01, Vol.36 (1), p.342-352 |
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| creator | Kumar, Nikhil Singh, Mithalesh Kumar Singh, Lata Lomi, Neiwete Meel, Rachna Pushker, Neelam Sen, Seema Kashyap, Seema |
| description | Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan–Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (
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| doi_str_mv | 10.1007/s13577-022-00808-z |
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p
<
0.05
). On Kaplan–Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.</description><identifier>ISSN: 1749-0774</identifier><identifier>ISSN: 0914-7470</identifier><identifier>EISSN: 1749-0774</identifier><identifier>DOI: 10.1007/s13577-022-00808-z</identifier><identifier>PMID: 36282437</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Antigens, Neoplasm - genetics ; Biomarkers ; Biomarkers, Tumor - genetics ; Biomedical and Life Sciences ; Cell Biology ; Disease management ; Gene expression ; Gynecology ; Humans ; Immunohistochemistry ; Life Sciences ; Medical prognosis ; Melanoma ; Melanoma - diagnosis ; Melanoma - genetics ; Metastases ; Metastasis ; Oncology ; Patients ; Reproductive Medicine ; Research Article ; Risk factors ; RNA, Messenger - genetics ; Statistical analysis ; Stem Cells ; Surgery ; Survival ; Survival analysis ; Transcription Factors ; Tumors</subject><ispartof>Human cell : official journal of Human Cell Research Society, 2023-01, Vol.36 (1), p.342-352</ispartof><rights>The Author(s) under exclusive licence to Japan Human Cell Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s) under exclusive licence to Japan Human Cell Society.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c329t-ef084931606f84abd837440ae848f4bd6d438e4ef8c87159c7f31997ba4cf4d63</citedby><cites>FETCH-LOGICAL-c329t-ef084931606f84abd837440ae848f4bd6d438e4ef8c87159c7f31997ba4cf4d63</cites><orcidid>0000-0002-8746-9017</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13577-022-00808-z$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13577-022-00808-z$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51298</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36282437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kumar, Nikhil</creatorcontrib><creatorcontrib>Singh, Mithalesh Kumar</creatorcontrib><creatorcontrib>Singh, Lata</creatorcontrib><creatorcontrib>Lomi, Neiwete</creatorcontrib><creatorcontrib>Meel, Rachna</creatorcontrib><creatorcontrib>Pushker, Neelam</creatorcontrib><creatorcontrib>Sen, Seema</creatorcontrib><creatorcontrib>Kashyap, Seema</creatorcontrib><title>Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients</title><title>Human cell : official journal of Human Cell Research Society</title><addtitle>Human Cell</addtitle><addtitle>Hum Cell</addtitle><description>Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan–Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (
p
<
0.05
). On Kaplan–Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.</description><subject>Antigens, Neoplasm - genetics</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biomedical and Life Sciences</subject><subject>Cell Biology</subject><subject>Disease management</subject><subject>Gene expression</subject><subject>Gynecology</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Life Sciences</subject><subject>Medical prognosis</subject><subject>Melanoma</subject><subject>Melanoma - diagnosis</subject><subject>Melanoma - genetics</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Oncology</subject><subject>Patients</subject><subject>Reproductive Medicine</subject><subject>Research Article</subject><subject>Risk factors</subject><subject>RNA, Messenger - genetics</subject><subject>Statistical analysis</subject><subject>Stem Cells</subject><subject>Surgery</subject><subject>Survival</subject><subject>Survival analysis</subject><subject>Transcription Factors</subject><subject>Tumors</subject><issn>1749-0774</issn><issn>0914-7470</issn><issn>1749-0774</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcuOFCEUhonROBd9AReGxI2bUgpOA7XszIyjyXjJRNeEpqCLsQpaoDQ9T-EjS9njJS7ccEjO9__nnPwIPWnJi5YQ8TK3bCVEQyhtCJFENrf30HEroGuIEHD_r_8ROsn5hhBYAacP0RHjVFJg4hh9P_d6G2Iu3uC5-NGXPY4O-2maQxx8LtEMdqo17bEP2MRgYup1MBZ_82XA0_W7NdZBj_vs86L8cL1-e7GgZbC4ynTxzpv6xrC0B78dmuTzZzx_tXrEkx11iJPGu4rYUPIj9MDpMdvHd_UUfXp18fHsdXP1_vLN2fqqMYx2pbGOSOhYywl3EvSml0wAEG0lSAebnvfApAXrpJGiXXVGONZ2ndhoMA56zk7R84PvLsUvs81F1SuNHes6Ns5ZUUElcM7Fgj77B72Jc6o3LxQnkoMAUSl6oEyKOSfr1C75Sae9aola8lKHvFTNS_3MS91W0dM763kz2f635FdAFWAHINdW2Nr0Z_Z_bH8A3jOjYA</recordid><startdate>20230101</startdate><enddate>20230101</enddate><creator>Kumar, Nikhil</creator><creator>Singh, Mithalesh Kumar</creator><creator>Singh, Lata</creator><creator>Lomi, Neiwete</creator><creator>Meel, Rachna</creator><creator>Pushker, Neelam</creator><creator>Sen, Seema</creator><creator>Kashyap, Seema</creator><general>Springer Nature Singapore</general><general>Springer Nature B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0002-8746-9017</orcidid></search><sort><creationdate>20230101</creationdate><title>Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients</title><author>Kumar, Nikhil ; Singh, Mithalesh Kumar ; Singh, Lata ; Lomi, Neiwete ; Meel, Rachna ; Pushker, Neelam ; Sen, Seema ; Kashyap, Seema</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c329t-ef084931606f84abd837440ae848f4bd6d438e4ef8c87159c7f31997ba4cf4d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antigens, Neoplasm - genetics</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biomedical and Life Sciences</topic><topic>Cell Biology</topic><topic>Disease management</topic><topic>Gene expression</topic><topic>Gynecology</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Life Sciences</topic><topic>Medical prognosis</topic><topic>Melanoma</topic><topic>Melanoma - diagnosis</topic><topic>Melanoma - genetics</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Oncology</topic><topic>Patients</topic><topic>Reproductive Medicine</topic><topic>Research Article</topic><topic>Risk factors</topic><topic>RNA, Messenger - genetics</topic><topic>Statistical analysis</topic><topic>Stem Cells</topic><topic>Surgery</topic><topic>Survival</topic><topic>Survival analysis</topic><topic>Transcription Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kumar, Nikhil</creatorcontrib><creatorcontrib>Singh, Mithalesh Kumar</creatorcontrib><creatorcontrib>Singh, Lata</creatorcontrib><creatorcontrib>Lomi, Neiwete</creatorcontrib><creatorcontrib>Meel, Rachna</creatorcontrib><creatorcontrib>Pushker, Neelam</creatorcontrib><creatorcontrib>Sen, Seema</creatorcontrib><creatorcontrib>Kashyap, Seema</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Human cell : official journal of Human Cell Research Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kumar, Nikhil</au><au>Singh, Mithalesh Kumar</au><au>Singh, Lata</au><au>Lomi, Neiwete</au><au>Meel, Rachna</au><au>Pushker, Neelam</au><au>Sen, Seema</au><au>Kashyap, Seema</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients</atitle><jtitle>Human cell : official journal of Human Cell Research Society</jtitle><stitle>Human Cell</stitle><addtitle>Hum Cell</addtitle><date>2023-01-01</date><risdate>2023</risdate><volume>36</volume><issue>1</issue><spage>342</spage><epage>352</epage><pages>342-352</pages><issn>1749-0774</issn><issn>0914-7470</issn><eissn>1749-0774</eissn><abstract>Existing clinical indicators for metastatic risk classification and patient treatment of uveal melanoma (UM) in the Asian population are limited. Preferentially expressed antigen in melanoma (PRAME) has gained attention in the prognosis of cancers and considered as a potential biomarker in many tumors including UM. Therefore, this study investigated the expression of PRAME and its association with loss of nuclear BAP1 (nBAP1) as well as its correlation with clinicopathological parameters and patient outcome. Immunohistochemical expression of PRAME and BAP1 proteins were assessed in 66 prospective cases of UM. mRNA expression level was measured by quantitative real-time PCR. Kaplan–Meier curves and Cox proportional hazard models were used to analyze the correlation of protein expression with clinicopathological parameters, metastasis-free survival and overall survival. Nuclear PRAME (nPRAME) expression and loss of nBAP1 were observed in 24 and 62% cases, respectively. PRAME mRNA expression level was found to be upregulated in 64% (7/11) of metastatic patients. mRNA and immunoexpression of nPRAME were statistically significant with many clinicopathological high-risk factors. On univariate and multivariate analyses, high mitotic activity, extraocular invasion and presence of nPRAME expression were statistically significant (
p
<
0.05
). On Kaplan–Meier survival analysis, patients expressing PRAME had significantly reduced metastasis-free survival (MFS) and overall survival (OS). MFS and OS were also reduced in patients expressing PRAME along with loss of nBAP1. Our data show that nPRAME expression, in combination with loss of nBAP1, could be a useful predictive biomarker in the therapeutic management of UM patients at high risk.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>36282437</pmid><doi>10.1007/s13577-022-00808-z</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-8746-9017</orcidid></addata></record> |
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| subjects | Antigens, Neoplasm - genetics Biomarkers Biomarkers, Tumor - genetics Biomedical and Life Sciences Cell Biology Disease management Gene expression Gynecology Humans Immunohistochemistry Life Sciences Medical prognosis Melanoma Melanoma - diagnosis Melanoma - genetics Metastases Metastasis Oncology Patients Reproductive Medicine Research Article Risk factors RNA, Messenger - genetics Statistical analysis Stem Cells Surgery Survival Survival analysis Transcription Factors Tumors |
| title | Diagnostic utility of immunohistochemistry in concordance with mRNA analysis of PRAME in the stratification of high-risk uveal melanoma patients |
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