Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue
Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used...
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Veröffentlicht in: | Experimental dermatology 2022-12, Vol.31 (12), p.1920-1926 |
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creator | Gleue, Casey A. Xie, Fangyi Deschaine, Maria Dasari, Surendra Sartori‐Valinotti, Julio C. Torgerson, Rochelle R. Davis, Mark D. P. Charlesworth, M. Cristine Meves, Alexander Lehman, Julia S. |
description | Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection‐ and nanoLC‐tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow‐up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon‐γ and antigen‐presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy‐related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets. |
doi_str_mv | 10.1111/exd.14660 |
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P. ; Charlesworth, M. Cristine ; Meves, Alexander ; Lehman, Julia S.</creator><creatorcontrib>Gleue, Casey A. ; Xie, Fangyi ; Deschaine, Maria ; Dasari, Surendra ; Sartori‐Valinotti, Julio C. ; Torgerson, Rochelle R. ; Davis, Mark D. P. ; Charlesworth, M. Cristine ; Meves, Alexander ; Lehman, Julia S.</creatorcontrib><description>Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection‐ and nanoLC‐tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow‐up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon‐γ and antigen‐presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy‐related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.</description><identifier>ISSN: 0906-6705</identifier><identifier>EISSN: 1600-0625</identifier><identifier>DOI: 10.1111/exd.14660</identifier><identifier>PMID: 35960231</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Calcium channels (voltage-gated) ; Carcinogenesis ; Carcinoma, Squamous Cell - metabolism ; Cell Transformation, Neoplastic ; Female ; Genital diseases ; Humans ; lichen sclerosus ; Malignancy ; Mass spectroscopy ; Proteomics ; Risk factors ; Squamous cell carcinoma ; Therapeutic targets ; Vulva ; vulvar lichen sclerosus ; Vulvar Lichen Sclerosus - complications ; Vulvar Lichen Sclerosus - metabolism ; Vulvar Lichen Sclerosus - pathology ; Vulvar Neoplasms - pathology ; vulvar squamous cell carcinoma ; women's health ; γ-Interferon</subject><ispartof>Experimental dermatology, 2022-12, Vol.31 (12), p.1920-1926</ispartof><rights>2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>2022 John Wiley & Sons A/S</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3530-b9fb5bf43ea54ef7098cab48e5d6d53cc7f83d524fa8d4b8e1efe1f9767e6ba43</citedby><cites>FETCH-LOGICAL-c3530-b9fb5bf43ea54ef7098cab48e5d6d53cc7f83d524fa8d4b8e1efe1f9767e6ba43</cites><orcidid>0000-0002-7389-3853 ; 0000-0001-5524-2750 ; 0000-0002-8965-5403</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fexd.14660$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fexd.14660$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35960231$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gleue, Casey A.</creatorcontrib><creatorcontrib>Xie, Fangyi</creatorcontrib><creatorcontrib>Deschaine, Maria</creatorcontrib><creatorcontrib>Dasari, Surendra</creatorcontrib><creatorcontrib>Sartori‐Valinotti, Julio C.</creatorcontrib><creatorcontrib>Torgerson, Rochelle R.</creatorcontrib><creatorcontrib>Davis, Mark D. P.</creatorcontrib><creatorcontrib>Charlesworth, M. Cristine</creatorcontrib><creatorcontrib>Meves, Alexander</creatorcontrib><creatorcontrib>Lehman, Julia S.</creatorcontrib><title>Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue</title><title>Experimental dermatology</title><addtitle>Exp Dermatol</addtitle><description>Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection‐ and nanoLC‐tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow‐up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon‐γ and antigen‐presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy‐related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.</description><subject>Calcium channels (voltage-gated)</subject><subject>Carcinogenesis</subject><subject>Carcinoma, Squamous Cell - metabolism</subject><subject>Cell Transformation, Neoplastic</subject><subject>Female</subject><subject>Genital diseases</subject><subject>Humans</subject><subject>lichen sclerosus</subject><subject>Malignancy</subject><subject>Mass spectroscopy</subject><subject>Proteomics</subject><subject>Risk factors</subject><subject>Squamous cell carcinoma</subject><subject>Therapeutic targets</subject><subject>Vulva</subject><subject>vulvar lichen sclerosus</subject><subject>Vulvar Lichen Sclerosus - complications</subject><subject>Vulvar Lichen Sclerosus - metabolism</subject><subject>Vulvar Lichen Sclerosus - pathology</subject><subject>Vulvar Neoplasms - pathology</subject><subject>vulvar squamous cell carcinoma</subject><subject>women's health</subject><subject>γ-Interferon</subject><issn>0906-6705</issn><issn>1600-0625</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10E1LwzAYB_AgipvTg19AAp4EuyXNS9ujbPMFBl4UvJW0faIZfZlJO7e7H9zMTm8LgVx-_J88f4QuKRlTfyawKcaUS0mO0JBKQgIiQ3GMhiQhMpAREQN05tySEBqxSJyiAROJJCGjQ_Q9M1qDhbo1qsQr27TQVCbHsFlZcM40NTa7WzSlN3jdlWtlcWnyD6ixy0uwjevcLW6tqp1ubGXq90MKq7rAtTd-0p60xrkOztGJVqWDi_07Qq_385fpY7B4fnia3i2CnAlGgizRmcg0Z6AEBx2RJM5VxmMQhSwEy_NIx6wQIdcqLngWAwUNVCeRjEBmirMRuu5z_Z6fHbg2XTadrf3INIw4EzQUQnp106vc_9pZ0OnKmkrZbUpJuus79X2nv317e7VP7LIKin_5V7AHkx58mRK2h5PS-dusj_wBcHuOlA</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Gleue, Casey A.</creator><creator>Xie, Fangyi</creator><creator>Deschaine, Maria</creator><creator>Dasari, Surendra</creator><creator>Sartori‐Valinotti, Julio C.</creator><creator>Torgerson, Rochelle R.</creator><creator>Davis, Mark D. P.</creator><creator>Charlesworth, M. Cristine</creator><creator>Meves, Alexander</creator><creator>Lehman, Julia S.</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0002-7389-3853</orcidid><orcidid>https://orcid.org/0000-0001-5524-2750</orcidid><orcidid>https://orcid.org/0000-0002-8965-5403</orcidid></search><sort><creationdate>202212</creationdate><title>Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue</title><author>Gleue, Casey A. ; Xie, Fangyi ; Deschaine, Maria ; Dasari, Surendra ; Sartori‐Valinotti, Julio C. ; Torgerson, Rochelle R. ; Davis, Mark D. P. ; Charlesworth, M. Cristine ; Meves, Alexander ; Lehman, Julia S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3530-b9fb5bf43ea54ef7098cab48e5d6d53cc7f83d524fa8d4b8e1efe1f9767e6ba43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Calcium channels (voltage-gated)</topic><topic>Carcinogenesis</topic><topic>Carcinoma, Squamous Cell - metabolism</topic><topic>Cell Transformation, Neoplastic</topic><topic>Female</topic><topic>Genital diseases</topic><topic>Humans</topic><topic>lichen sclerosus</topic><topic>Malignancy</topic><topic>Mass spectroscopy</topic><topic>Proteomics</topic><topic>Risk factors</topic><topic>Squamous cell carcinoma</topic><topic>Therapeutic targets</topic><topic>Vulva</topic><topic>vulvar lichen sclerosus</topic><topic>Vulvar Lichen Sclerosus - complications</topic><topic>Vulvar Lichen Sclerosus - metabolism</topic><topic>Vulvar Lichen Sclerosus - pathology</topic><topic>Vulvar Neoplasms - pathology</topic><topic>vulvar squamous cell carcinoma</topic><topic>women's health</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gleue, Casey A.</creatorcontrib><creatorcontrib>Xie, Fangyi</creatorcontrib><creatorcontrib>Deschaine, Maria</creatorcontrib><creatorcontrib>Dasari, Surendra</creatorcontrib><creatorcontrib>Sartori‐Valinotti, Julio C.</creatorcontrib><creatorcontrib>Torgerson, Rochelle R.</creatorcontrib><creatorcontrib>Davis, Mark D. P.</creatorcontrib><creatorcontrib>Charlesworth, M. Cristine</creatorcontrib><creatorcontrib>Meves, Alexander</creatorcontrib><creatorcontrib>Lehman, Julia S.</creatorcontrib><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>AIDS and Cancer Research Abstracts</collection><jtitle>Experimental dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gleue, Casey A.</au><au>Xie, Fangyi</au><au>Deschaine, Maria</au><au>Dasari, Surendra</au><au>Sartori‐Valinotti, Julio C.</au><au>Torgerson, Rochelle R.</au><au>Davis, Mark D. P.</au><au>Charlesworth, M. Cristine</au><au>Meves, Alexander</au><au>Lehman, Julia S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue</atitle><jtitle>Experimental dermatology</jtitle><addtitle>Exp Dermatol</addtitle><date>2022-12</date><risdate>2022</risdate><volume>31</volume><issue>12</issue><spage>1920</spage><epage>1926</epage><pages>1920-1926</pages><issn>0906-6705</issn><eissn>1600-0625</eissn><abstract>Vulvar lichen sclerosus (VLS) confers approximately 3% risk of malignant transformation to vulvar squamous cell carcinoma (VSCC). We used unbiased proteomic methods to identify differentially expressed proteins in tissue of patients with VLS who developed VSCC compared to those who did not. We used laser capture microdissection‐ and nanoLC‐tandem mass spectrometry to assess protein expression in individuals in normal vulvar tissue (NVT, n = 4), indolent VLS (no VSCC after at least 5 years follow‐up, n = 5) or transforming VSCC (preceding VSCC, n = 5). Interferon‐γ and antigen‐presenting pathways are overexpressed in indolent and transforming VLS compared to NVT. There was differential expression of malignancy‐related proteins in transforming VLS compared to indolent VLS (CAV1 overexpression, AKAP12 underexpression), particularly in the EIF2 translation pathway, which has been previously implicated in carcinogenesis. Results of this study provide additional molecular evidence supporting the concept that VLS is a risk factor for VSCC and highlights possible future biomarkers and/or therapeutic targets.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>35960231</pmid><doi>10.1111/exd.14660</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0002-7389-3853</orcidid><orcidid>https://orcid.org/0000-0001-5524-2750</orcidid><orcidid>https://orcid.org/0000-0002-8965-5403</orcidid></addata></record> |
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subjects | Calcium channels (voltage-gated) Carcinogenesis Carcinoma, Squamous Cell - metabolism Cell Transformation, Neoplastic Female Genital diseases Humans lichen sclerosus Malignancy Mass spectroscopy Proteomics Risk factors Squamous cell carcinoma Therapeutic targets Vulva vulvar lichen sclerosus Vulvar Lichen Sclerosus - complications Vulvar Lichen Sclerosus - metabolism Vulvar Lichen Sclerosus - pathology Vulvar Neoplasms - pathology vulvar squamous cell carcinoma women's health γ-Interferon |
title | Differential proteomic expression in indolent vulvar lichen sclerosus, transforming vulvar lichen sclerosus and normal vulvar tissue |
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