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The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival

SIMPLE SUMMARY: Although many immunotherapies produce positive initial clinical responses, most advanced cancer patients recur so that there is an urgent need to identify and counteract both the intrinsic resistance as well as acquired mechanisms. During our studies on the mechanisms of resistance,...

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Autores principales: Ogata, Dai, Roszik, Jason, Oba, Junna, Kim, Sun-Hee, Bassett, Roland L., Haydu, Lauren E., Tanese, Keiji, Grimm, Elizabeth A., Ekmekcioglu, Suhendan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764866/
https://www.ncbi.nlm.nih.gov/pubmed/33327409
http://dx.doi.org/10.3390/cancers12123754
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author Ogata, Dai
Roszik, Jason
Oba, Junna
Kim, Sun-Hee
Bassett, Roland L.
Haydu, Lauren E.
Tanese, Keiji
Grimm, Elizabeth A.
Ekmekcioglu, Suhendan
author_facet Ogata, Dai
Roszik, Jason
Oba, Junna
Kim, Sun-Hee
Bassett, Roland L.
Haydu, Lauren E.
Tanese, Keiji
Grimm, Elizabeth A.
Ekmekcioglu, Suhendan
author_sort Ogata, Dai
collection PubMed
description SIMPLE SUMMARY: Although many immunotherapies produce positive initial clinical responses, most advanced cancer patients recur so that there is an urgent need to identify and counteract both the intrinsic resistance as well as acquired mechanisms. During our studies on the mechanisms of resistance, we have identified a set of related protein markers, which we now employ to generate a useful signature of, associated with microenvironmental oxidative stress. Our study examines inflammatory marker expression in stage IV melanoma that are associated with survival outcome and risk of developing central nervous system (CNS) metastasis. Our data here presents CD74 as a prognostic tumor marker associated with good survival in stage IV melanoma. Additionally, the tumor cell nitrotyrosine (NT) expression predicts a greater risk of developing CNS metastasis in those patients. Our understanding of complex cancer cell and their response in the chronic inflammation environment would help us develop better treatments for melanoma. ABSTRACT: Innate inflammatory features have been found in melanoma tumors from patients at all stages, and molecular analysis has identified definitive inflammatory proteins expressed by tumors cells in patients who presents the worst prognosis. We have previously observed weakened outcomes in patients with constitutive expression of inducible nitric oxide synthase (iNOS), macrophage migration inhibitory factor (MIF) and improved outcomes with CD74 expression in stage III melanoma. In our current study, we tested our hypothesis on CD74-regulated inflammatory markers’ expression in stage IV melanoma tumors whether the signature is associated with survival outcome and/or risk of developing CNS metastasis. We retrospectively identified 315 patients with stage IV melanoma. In a tissue microarray (TMA), we examined the expression of cells with CD74, its receptor MIF, and downstream inflammatory markers iNOS, nitrotyrosine (NT), cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES1). We analyzed the association of those inflammatory markers with overall survival time (OS) and time to CNS metastasis using Kaplan–Meier survival analyses. Our data validates CD74 as a useful prognostic tumor cell protein marker associated with favorable OS as in stage III melanomas, while the tumor NT expression strongly predicts an increased risk of developing CNS metastasis (p = 0.0008) in those patients.
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spelling pubmed-77648662020-12-27 The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival Ogata, Dai Roszik, Jason Oba, Junna Kim, Sun-Hee Bassett, Roland L. Haydu, Lauren E. Tanese, Keiji Grimm, Elizabeth A. Ekmekcioglu, Suhendan Cancers (Basel) Article SIMPLE SUMMARY: Although many immunotherapies produce positive initial clinical responses, most advanced cancer patients recur so that there is an urgent need to identify and counteract both the intrinsic resistance as well as acquired mechanisms. During our studies on the mechanisms of resistance, we have identified a set of related protein markers, which we now employ to generate a useful signature of, associated with microenvironmental oxidative stress. Our study examines inflammatory marker expression in stage IV melanoma that are associated with survival outcome and risk of developing central nervous system (CNS) metastasis. Our data here presents CD74 as a prognostic tumor marker associated with good survival in stage IV melanoma. Additionally, the tumor cell nitrotyrosine (NT) expression predicts a greater risk of developing CNS metastasis in those patients. Our understanding of complex cancer cell and their response in the chronic inflammation environment would help us develop better treatments for melanoma. ABSTRACT: Innate inflammatory features have been found in melanoma tumors from patients at all stages, and molecular analysis has identified definitive inflammatory proteins expressed by tumors cells in patients who presents the worst prognosis. We have previously observed weakened outcomes in patients with constitutive expression of inducible nitric oxide synthase (iNOS), macrophage migration inhibitory factor (MIF) and improved outcomes with CD74 expression in stage III melanoma. In our current study, we tested our hypothesis on CD74-regulated inflammatory markers’ expression in stage IV melanoma tumors whether the signature is associated with survival outcome and/or risk of developing CNS metastasis. We retrospectively identified 315 patients with stage IV melanoma. In a tissue microarray (TMA), we examined the expression of cells with CD74, its receptor MIF, and downstream inflammatory markers iNOS, nitrotyrosine (NT), cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1 (mPGES1). We analyzed the association of those inflammatory markers with overall survival time (OS) and time to CNS metastasis using Kaplan–Meier survival analyses. Our data validates CD74 as a useful prognostic tumor cell protein marker associated with favorable OS as in stage III melanomas, while the tumor NT expression strongly predicts an increased risk of developing CNS metastasis (p = 0.0008) in those patients. MDPI 2020-12-14 /pmc/articles/PMC7764866/ /pubmed/33327409 http://dx.doi.org/10.3390/cancers12123754 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ogata, Dai
Roszik, Jason
Oba, Junna
Kim, Sun-Hee
Bassett, Roland L.
Haydu, Lauren E.
Tanese, Keiji
Grimm, Elizabeth A.
Ekmekcioglu, Suhendan
The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title_full The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title_fullStr The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title_full_unstemmed The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title_short The Expression of CD74-Regulated Inflammatory Markers in Stage IV Melanoma: Risk of CNS Metastasis and Patient Survival
title_sort expression of cd74-regulated inflammatory markers in stage iv melanoma: risk of cns metastasis and patient survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764866/
https://www.ncbi.nlm.nih.gov/pubmed/33327409
http://dx.doi.org/10.3390/cancers12123754
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