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Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration

Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in si...

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Autores principales: Bezrookove, Vladimir, De Semir, David, Nosrati, Mehdi, Tong, Schuyler, Wu, Clayton, Thummala, Suresh, Dar, Altaf A., Leong, Stanley P.L., Cleaver, James E., Sagebiel, Richard W., Miller, James R., Kashani-Sabet, Mohammed
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945648/
https://www.ncbi.nlm.nih.gov/pubmed/24005052
http://dx.doi.org/10.1038/jid.2013.369
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author Bezrookove, Vladimir
De Semir, David
Nosrati, Mehdi
Tong, Schuyler
Wu, Clayton
Thummala, Suresh
Dar, Altaf A.
Leong, Stanley P.L.
Cleaver, James E.
Sagebiel, Richard W.
Miller, James R.
Kashani-Sabet, Mohammed
author_facet Bezrookove, Vladimir
De Semir, David
Nosrati, Mehdi
Tong, Schuyler
Wu, Clayton
Thummala, Suresh
Dar, Altaf A.
Leong, Stanley P.L.
Cleaver, James E.
Sagebiel, Richard W.
Miller, James R.
Kashani-Sabet, Mohammed
author_sort Bezrookove, Vladimir
collection PubMed
description Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis.
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spelling pubmed-39456482014-09-01 Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration Bezrookove, Vladimir De Semir, David Nosrati, Mehdi Tong, Schuyler Wu, Clayton Thummala, Suresh Dar, Altaf A. Leong, Stanley P.L. Cleaver, James E. Sagebiel, Richard W. Miller, James R. Kashani-Sabet, Mohammed J Invest Dermatol Article Ulceration is an important prognostic factor in melanoma whose biologic basis is poorly understood. Here we assessed the prognostic impact of pleckstrin homology domain-interacting protein (PHIP) copy number and its relationship to ulceration. PHIP copy number was determined using fluorescence in situ hybridization (FISH) in a tissue microarray cohort of 238 melanomas. Elevated PHIP copy number was associated with significantly reduced DMFS (P = 0.01) and DSS (P = 0.009) by Kaplan-Meier analyses. PHIP FISH scores were independently predictive of DMFS (P = 0.03) and DSS (P = 0.03). Increased PHIP copy number was an independent predictor of ulceration status (P = 0.04). The combined impact of increased PHIP copy number and tumor vascularity on ulceration status was highly significant (P< 0.0001). Stable suppression of PHIP in human melanoma cells resulted in significantly reduced glycolytic activity in vitro, with lower expression of LDH5, HIF1A, and VEGF, and was accompanied by reduced microvessel density in vivo. These results provide further support for PHIP as a molecular prognostic marker of melanoma, and reveal a significant linkage between PHIP levels and ulceration. Moreover, they suggest that ulceration may be driven by increased glycolysis and angiogenesis. 2013-09-04 2014-03 /pmc/articles/PMC3945648/ /pubmed/24005052 http://dx.doi.org/10.1038/jid.2013.369 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Bezrookove, Vladimir
De Semir, David
Nosrati, Mehdi
Tong, Schuyler
Wu, Clayton
Thummala, Suresh
Dar, Altaf A.
Leong, Stanley P.L.
Cleaver, James E.
Sagebiel, Richard W.
Miller, James R.
Kashani-Sabet, Mohammed
Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title_full Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title_fullStr Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title_full_unstemmed Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title_short Prognostic Impact of PHIP Copy Number in Melanoma: Linkage to Ulceration
title_sort prognostic impact of phip copy number in melanoma: linkage to ulceration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945648/
https://www.ncbi.nlm.nih.gov/pubmed/24005052
http://dx.doi.org/10.1038/jid.2013.369
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