Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation
Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients. In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastati...
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| creator | Garrisi, Vito Michele Strippoli, Sabino De Summa, Simona Pinto, Rosamaria Perrone, Antonella Guida, Gabriella Azzariti, Amalia Guida, Michele Tommasi, Stefania Stefania, Tommasi |
| description | Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients.
In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.
In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.
Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma. |
| doi_str_mv | 10.1371/journal.pone.0112025 |
| format | Article |
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In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.
In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.
Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0112025</identifier><identifier>PMID: 25437182</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Apoptosis ; Bioindicators ; Biology and Life Sciences ; Biomarkers ; Chemotherapy ; Computer Simulation ; Deregulation ; Detoxification ; Disease control ; Female ; Humans ; Indoles - pharmacology ; Indoles - therapeutic use ; Invasiveness ; Male ; Medicine and Health Sciences ; Melanoma ; Melanoma - drug therapy ; Melanoma - genetics ; Melanoma - metabolism ; Melanoma - pathology ; Metastases ; Middle Aged ; Mutation ; Neoplasm Metastasis ; Neuromodulation ; Neuroplasticity ; Patients ; Peptides ; Plasticity (neural) ; Proteins ; Proteomics ; Proto-Oncogene Proteins B-raf - genetics ; Research and Analysis Methods ; Sulfonamides - pharmacology ; Sulfonamides - therapeutic use ; Technology assessment ; Transcription ; Transcription factors</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e112025-e112025</ispartof><rights>2014 Garrisi 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>2014 Garrisi et al 2014 Garrisi et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-f77a7daa32fa0e65e5c6a69e27dfaf98ac7862cf6c5a76d35780c768d77650ea3</citedby><cites>FETCH-LOGICAL-c526t-f77a7daa32fa0e65e5c6a69e27dfaf98ac7862cf6c5a76d35780c768d77650ea3</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/PMC4249853/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4249853/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25437182$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Chammas, Roger</contributor><creatorcontrib>Garrisi, Vito Michele</creatorcontrib><creatorcontrib>Strippoli, Sabino</creatorcontrib><creatorcontrib>De Summa, Simona</creatorcontrib><creatorcontrib>Pinto, Rosamaria</creatorcontrib><creatorcontrib>Perrone, Antonella</creatorcontrib><creatorcontrib>Guida, Gabriella</creatorcontrib><creatorcontrib>Azzariti, Amalia</creatorcontrib><creatorcontrib>Guida, Michele</creatorcontrib><creatorcontrib>Tommasi, Stefania</creatorcontrib><creatorcontrib>Stefania, Tommasi</creatorcontrib><title>Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Selective inhibitors of BRAF, vemurafenib and dabrafenib are the standard of care for metastatic melanoma patients with BRAF V600, while chemotherapy continued to be widely used in BRAF wild type patients.
In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.
In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.
Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>Bioindicators</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Chemotherapy</subject><subject>Computer Simulation</subject><subject>Deregulation</subject><subject>Detoxification</subject><subject>Disease control</subject><subject>Female</subject><subject>Humans</subject><subject>Indoles - pharmacology</subject><subject>Indoles - therapeutic use</subject><subject>Invasiveness</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - 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In order to discover novel candidate biomarkers predictive to treatment, serum of 39 metastatic melanoma vemurafenib (n = 19) or chemotherapy (n = 20) treated patients at baseline, at disease control and at progression, were analyzed using SELDI-TOF technology. In silico analysis was used to identify more significant peaks.
In patients with different BRAF status, we found 5 peptides significantly deregulated, with the down-regulation of the m/z 9176 peak strongly associated with BRAF mutation. At baseline as predictive biomarkers we identified 2 peptides - m/z 6411, 4075 - as significantly up-regulated in responders to chemotherapy and 4 peaks - m/z 5900, 12544, 49124 and 11724 - significantly up-regulated in longer vs shorter responders to vemurafenib. After response, 3 peptides (m/z 4658, 18639, and 9307) resulted significantly down regulated while 3 peptides m/z 9292, 7765 and 9176 appeared up-regulated respectively in chemotherapy and vemurafenib responder patients. In vemurafenib treated patients, 16 peaks appeared deregulated at progression compared to baseline time. In silico analysis identified proteins involved in invasiveness (SLAIN1) and resistance (ABCC12) as well as in the pathway of detoxification (NQO1) and apoptosis (RBM10, TOX3, MTEFD1, TSPO2). Proteins associated with the modulation of neuronal plasticity (RIN1) and regulatory activity factors of gene transcription (KLF17, ZBTB44) were also highlighted.
Our exploratory study highlighted some factors that deserve to be further investigated in order to provide a framework for improving melanoma treatment management through the development of biomarkers which could act as the strongest surrogates of the key biological events in stage IV melanoma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25437182</pmid><doi>10.1371/journal.pone.0112025</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2014-12, Vol.9 (12), p.e112025-e112025 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1629337930 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adult Aged Aged, 80 and over Apoptosis Bioindicators Biology and Life Sciences Biomarkers Chemotherapy Computer Simulation Deregulation Detoxification Disease control Female Humans Indoles - pharmacology Indoles - therapeutic use Invasiveness Male Medicine and Health Sciences Melanoma Melanoma - drug therapy Melanoma - genetics Melanoma - metabolism Melanoma - pathology Metastases Middle Aged Mutation Neoplasm Metastasis Neuromodulation Neuroplasticity Patients Peptides Plasticity (neural) Proteins Proteomics Proto-Oncogene Proteins B-raf - genetics Research and Analysis Methods Sulfonamides - pharmacology Sulfonamides - therapeutic use Technology assessment Transcription Transcription factors |
| title | Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-25T11%3A53%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Proteomic%20profile%20and%20in%20silico%20analysis%20in%20metastatic%20melanoma%20with%20and%20without%20BRAF%20mutation&rft.jtitle=PloS%20one&rft.au=Garrisi,%20Vito%20Michele&rft.date=2014-12-01&rft.volume=9&rft.issue=12&rft.spage=e112025&rft.epage=e112025&rft.pages=e112025-e112025&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0112025&rft_dat=%3Cproquest_plos_%3E3512957611%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1629337930&rft_id=info:pmid/25437182&rft_doaj_id=oai_doaj_org_article_0f175585ca93466cb910dcfbd537a834&rfr_iscdi=true |