Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/179381 |
Resumo: | Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes to most human melanoma-related deaths. Recently, overlapping groups of proteins and pathways were shown to regulate stem cell migration and cancer metastasis, raising the question of whether genes/proteins involved in stem cell pluripotency may have important implications when applied to the biology of cancer metastasis. Furthermore, it is well known that ion channels and receptors, particularly those responsible for calcium (Ca2+) signal generation, are critical in determining the cellular fate of stem cells (SCs). In the present study, we searched for evidence of altered stem cell pluripotency and Ca2+ signaling-related genes in the context of melanoma metastasis. We did this by using network analysis of gene expression in tissue biopsies from three different independent datasets of patients. First, we created an in silico network model (“STEMCa” interactome) showing the landscape of interactions between stem cell pluripotency and Ca2+ signaling-related genes/proteins, and demonstrated that around 51% (151 out of 294) of the genes within this model displayed significant changes of expression (False Discovery Rate (FDR), corrected p-value < 0.05) in at least one of the datasets of melanoma metastasis when compared with primary tumor biopsies (controls). Analysis of the properties (degree and betweenness) of the topological network revealed 27 members as the most central hub (HB) and nonhub-bottlenecks (NH-B) among the 294 genes/proteins of the whole interactome. From those representative genes, CTNNB1, GNAQ, GSK3B, GSTP1, MAPK3, PPP1CC, PRKACA, and SMAD4 showed equal up- or downregulation (corrected p-value < 0.05) in at least 2 independent datasets of melanoma metastases samples and PTPN11 showed upregulation (corrected p-value < 0.05) in three of them when compared with control samples. We postulate that altered expression of stem cell pluripotency and Ca2+ signaling pathway-related genes may contribute to the metastatic transformation, with these central members being an optimal candidate group of biomarkers and in silico therapeutic targets for melanoma metastasis, which deserve further investigation. |
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Oliveira, Ben Hur Neves deDalmaz, CarlaZeidán-Chuliá, Fares2018-06-15T02:47:56Z20182076-3271http://hdl.handle.net/10183/179381001065415Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes to most human melanoma-related deaths. Recently, overlapping groups of proteins and pathways were shown to regulate stem cell migration and cancer metastasis, raising the question of whether genes/proteins involved in stem cell pluripotency may have important implications when applied to the biology of cancer metastasis. Furthermore, it is well known that ion channels and receptors, particularly those responsible for calcium (Ca2+) signal generation, are critical in determining the cellular fate of stem cells (SCs). In the present study, we searched for evidence of altered stem cell pluripotency and Ca2+ signaling-related genes in the context of melanoma metastasis. We did this by using network analysis of gene expression in tissue biopsies from three different independent datasets of patients. First, we created an in silico network model (“STEMCa” interactome) showing the landscape of interactions between stem cell pluripotency and Ca2+ signaling-related genes/proteins, and demonstrated that around 51% (151 out of 294) of the genes within this model displayed significant changes of expression (False Discovery Rate (FDR), corrected p-value < 0.05) in at least one of the datasets of melanoma metastasis when compared with primary tumor biopsies (controls). Analysis of the properties (degree and betweenness) of the topological network revealed 27 members as the most central hub (HB) and nonhub-bottlenecks (NH-B) among the 294 genes/proteins of the whole interactome. From those representative genes, CTNNB1, GNAQ, GSK3B, GSTP1, MAPK3, PPP1CC, PRKACA, and SMAD4 showed equal up- or downregulation (corrected p-value < 0.05) in at least 2 independent datasets of melanoma metastases samples and PTPN11 showed upregulation (corrected p-value < 0.05) in three of them when compared with control samples. We postulate that altered expression of stem cell pluripotency and Ca2+ signaling pathway-related genes may contribute to the metastatic transformation, with these central members being an optimal candidate group of biomarkers and in silico therapeutic targets for melanoma metastasis, which deserve further investigation.application/pdfengMedical Sciences. Basel. Vol. 6, no. 1 (Mar. 2018), artigo 23, 12 f.Biologia de sistemasBiomarcadoresNeoplasiasCélulas-tronco neoplásicasPluripotencyStemnessCalciumMalignancyBiomarkerSystems biologyNetwork-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanomaEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSORIGINAL001065415.pdf001065415.pdfTexto completo (inglês)application/pdf2475972http://www.lume.ufrgs.br/bitstream/10183/179381/1/001065415.pdfaa7df03d6f6b9f9a78030484215f0cecMD51TEXT001065415.pdf.txt001065415.pdf.txtExtracted Texttext/plain52499http://www.lume.ufrgs.br/bitstream/10183/179381/2/001065415.pdf.txt5b2f095c776d6573e0daa748c3eca783MD5210183/1793812021-03-09 04:25:51.816665oai:www.lume.ufrgs.br:10183/179381Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2021-03-09T07:25:51Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
title |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
spellingShingle |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma Oliveira, Ben Hur Neves de Biologia de sistemas Biomarcadores Neoplasias Células-tronco neoplásicas Pluripotency Stemness Calcium Malignancy Biomarker Systems biology |
title_short |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
title_full |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
title_fullStr |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
title_full_unstemmed |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
title_sort |
Network-based identification of altered stem cell pluripotency and calcium signaling pathways in metastatic melanoma |
author |
Oliveira, Ben Hur Neves de |
author_facet |
Oliveira, Ben Hur Neves de Dalmaz, Carla Zeidán-Chuliá, Fares |
author_role |
author |
author2 |
Dalmaz, Carla Zeidán-Chuliá, Fares |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Oliveira, Ben Hur Neves de Dalmaz, Carla Zeidán-Chuliá, Fares |
dc.subject.por.fl_str_mv |
Biologia de sistemas Biomarcadores Neoplasias Células-tronco neoplásicas |
topic |
Biologia de sistemas Biomarcadores Neoplasias Células-tronco neoplásicas Pluripotency Stemness Calcium Malignancy Biomarker Systems biology |
dc.subject.eng.fl_str_mv |
Pluripotency Stemness Calcium Malignancy Biomarker Systems biology |
description |
Malignancy of cancer has been linked to distinct subsets of stem-like cells, the so-called cancer stem cells (CSCs), which persist during treatment and seem to lead to drug-resistant recurrence. Metastatic spread of cancer cells is one of the hallmarks of malignancy and contributes to most human melanoma-related deaths. Recently, overlapping groups of proteins and pathways were shown to regulate stem cell migration and cancer metastasis, raising the question of whether genes/proteins involved in stem cell pluripotency may have important implications when applied to the biology of cancer metastasis. Furthermore, it is well known that ion channels and receptors, particularly those responsible for calcium (Ca2+) signal generation, are critical in determining the cellular fate of stem cells (SCs). In the present study, we searched for evidence of altered stem cell pluripotency and Ca2+ signaling-related genes in the context of melanoma metastasis. We did this by using network analysis of gene expression in tissue biopsies from three different independent datasets of patients. First, we created an in silico network model (“STEMCa” interactome) showing the landscape of interactions between stem cell pluripotency and Ca2+ signaling-related genes/proteins, and demonstrated that around 51% (151 out of 294) of the genes within this model displayed significant changes of expression (False Discovery Rate (FDR), corrected p-value < 0.05) in at least one of the datasets of melanoma metastasis when compared with primary tumor biopsies (controls). Analysis of the properties (degree and betweenness) of the topological network revealed 27 members as the most central hub (HB) and nonhub-bottlenecks (NH-B) among the 294 genes/proteins of the whole interactome. From those representative genes, CTNNB1, GNAQ, GSK3B, GSTP1, MAPK3, PPP1CC, PRKACA, and SMAD4 showed equal up- or downregulation (corrected p-value < 0.05) in at least 2 independent datasets of melanoma metastases samples and PTPN11 showed upregulation (corrected p-value < 0.05) in three of them when compared with control samples. We postulate that altered expression of stem cell pluripotency and Ca2+ signaling pathway-related genes may contribute to the metastatic transformation, with these central members being an optimal candidate group of biomarkers and in silico therapeutic targets for melanoma metastasis, which deserve further investigation. |
publishDate |
2018 |
dc.date.accessioned.fl_str_mv |
2018-06-15T02:47:56Z |
dc.date.issued.fl_str_mv |
2018 |
dc.type.driver.fl_str_mv |
Estrangeiro info:eu-repo/semantics/article |
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info:eu-repo/semantics/publishedVersion |
format |
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publishedVersion |
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http://hdl.handle.net/10183/179381 |
dc.identifier.issn.pt_BR.fl_str_mv |
2076-3271 |
dc.identifier.nrb.pt_BR.fl_str_mv |
001065415 |
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2076-3271 001065415 |
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http://hdl.handle.net/10183/179381 |
dc.language.iso.fl_str_mv |
eng |
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eng |
dc.relation.ispartof.pt_BR.fl_str_mv |
Medical Sciences. Basel. Vol. 6, no. 1 (Mar. 2018), artigo 23, 12 f. |
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info:eu-repo/semantics/openAccess |
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