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Correlation of histopathologic characteristics to protein expression and function in malignant melanoma

BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue sa...

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Autores principales: Welinder, Charlotte, Pawłowski, Krzysztof, Szasz, A. Marcell, Yakovleva, Maria, Sugihara, Yutaka, Malm, Johan, Jönsson, Göran, Ingvar, Christian, Lundgren, Lotta, Baldetorp, Bo, Olsson, Håkan, Rezeli, Melinda, Laurell, Thomas, Wieslander, Elisabet, Marko-Varga, György
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405986/
https://www.ncbi.nlm.nih.gov/pubmed/28445515
http://dx.doi.org/10.1371/journal.pone.0176167
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author Welinder, Charlotte
Pawłowski, Krzysztof
Szasz, A. Marcell
Yakovleva, Maria
Sugihara, Yutaka
Malm, Johan
Jönsson, Göran
Ingvar, Christian
Lundgren, Lotta
Baldetorp, Bo
Olsson, Håkan
Rezeli, Melinda
Laurell, Thomas
Wieslander, Elisabet
Marko-Varga, György
author_facet Welinder, Charlotte
Pawłowski, Krzysztof
Szasz, A. Marcell
Yakovleva, Maria
Sugihara, Yutaka
Malm, Johan
Jönsson, Göran
Ingvar, Christian
Lundgren, Lotta
Baldetorp, Bo
Olsson, Håkan
Rezeli, Melinda
Laurell, Thomas
Wieslander, Elisabet
Marko-Varga, György
author_sort Welinder, Charlotte
collection PubMed
description BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. PATIENTS AND METHODS: Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease. RESULTS: In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. CONCLUSION: In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma.
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spelling pubmed-54059862017-05-14 Correlation of histopathologic characteristics to protein expression and function in malignant melanoma Welinder, Charlotte Pawłowski, Krzysztof Szasz, A. Marcell Yakovleva, Maria Sugihara, Yutaka Malm, Johan Jönsson, Göran Ingvar, Christian Lundgren, Lotta Baldetorp, Bo Olsson, Håkan Rezeli, Melinda Laurell, Thomas Wieslander, Elisabet Marko-Varga, György PLoS One Research Article BACKGROUND: Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. PATIENTS AND METHODS: Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease. RESULTS: In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival. CONCLUSION: In this feasibility study, promising results show the feasibility of relating proteomics to histopathology and clinical outcome, and insight thus can be gained into the molecular processes driving the disease. The combined analysis of histological features including the sample cellular composition with protein expression of each metastasis enabled the identification of novel, differentially expressed proteins. Further studies are necessary to determine whether these putative biomarkers can be utilized in diagnostics and prognostic prediction of metastatic melanoma. Public Library of Science 2017-04-26 /pmc/articles/PMC5405986/ /pubmed/28445515 http://dx.doi.org/10.1371/journal.pone.0176167 Text en © 2017 Welinder et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Welinder, Charlotte
Pawłowski, Krzysztof
Szasz, A. Marcell
Yakovleva, Maria
Sugihara, Yutaka
Malm, Johan
Jönsson, Göran
Ingvar, Christian
Lundgren, Lotta
Baldetorp, Bo
Olsson, Håkan
Rezeli, Melinda
Laurell, Thomas
Wieslander, Elisabet
Marko-Varga, György
Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title_full Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title_fullStr Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title_full_unstemmed Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title_short Correlation of histopathologic characteristics to protein expression and function in malignant melanoma
title_sort correlation of histopathologic characteristics to protein expression and function in malignant melanoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405986/
https://www.ncbi.nlm.nih.gov/pubmed/28445515
http://dx.doi.org/10.1371/journal.pone.0176167
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