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An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers

Breast, ovarian, and endometrial cancers have a major impact on mortality in women. These tumors share hormone-dependent mechanisms involved in female-specific cancers which support tumor growth in a different manner. Integrated computational approaches may allow us to better detect genomic similari...

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Autores principales: Pane, Katia, Affinito, Ornella, Zanfardino, Mario, Castaldo, Rossana, Incoronato, Mariarosaria, Salvatore, Marco, Franzese, Monica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793872/
https://www.ncbi.nlm.nih.gov/pubmed/33424936
http://dx.doi.org/10.3389/fgene.2020.612521
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author Pane, Katia
Affinito, Ornella
Zanfardino, Mario
Castaldo, Rossana
Incoronato, Mariarosaria
Salvatore, Marco
Franzese, Monica
author_facet Pane, Katia
Affinito, Ornella
Zanfardino, Mario
Castaldo, Rossana
Incoronato, Mariarosaria
Salvatore, Marco
Franzese, Monica
author_sort Pane, Katia
collection PubMed
description Breast, ovarian, and endometrial cancers have a major impact on mortality in women. These tumors share hormone-dependent mechanisms involved in female-specific cancers which support tumor growth in a different manner. Integrated computational approaches may allow us to better detect genomic similarities between these different female-specific cancers, helping us to deliver more sophisticated diagnosis and precise treatments. Recently, several initiatives of The Cancer Genome Atlas (TCGA) have encouraged integrated analyses of multiple cancers rather than individual tumors. These studies revealed common genetic alterations (driver genes) even in clinically distinct entities such as breast, ovarian, and endometrial cancers. In this study, we aimed to identify expression similarity signatures by extracting common genes among TCGA breast (BRCA), ovarian (OV), and uterine corpus endometrial carcinoma (UCEC) cohorts and infer co-regulatory protein–protein interaction networks that might have a relationship with the estrogen signaling pathway. Thus, we carried out an unsupervised principal component analysis (PCA)-based computational approach, using RNA sequencing data of 2,015 female cancer and 148 normal samples, in order to simultaneously capture the data heterogeneity of intertumors. Firstly, we identified tumor-associated genes from gene expression profiles. Secondly, we investigated the signaling pathways and co-regulatory protein–protein interaction networks underlying these three cancers by leveraging the Ingenuity Pathway Analysis software. In detail, we discovered 1,643 expression similarity signatures (638 downregulated and 1,005 upregulated genes, with respect to normal phenotype), denoted as tumor-associated genes. Through functional genomic analyses, we assessed that these genes were involved in the regulation of cell-cycle-dependent mechanisms, including metaphase kinetochore formation and estrogen-dependent S-phase entry. Furthermore, we generated putative co-regulatory protein–protein interaction networks, based on upstream regulators such as the ERBB2/HER2 gene. Moreover, we provided an ad-hoc bioinformatics workflow with a manageable list of intertumor expression similarity signatures for the three female-specific cancers. The expression similarity signatures identified in this study might uncover potential estrogen-dependent molecular mechanisms promoting carcinogenesis.
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spelling pubmed-77938722021-01-09 An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers Pane, Katia Affinito, Ornella Zanfardino, Mario Castaldo, Rossana Incoronato, Mariarosaria Salvatore, Marco Franzese, Monica Front Genet Genetics Breast, ovarian, and endometrial cancers have a major impact on mortality in women. These tumors share hormone-dependent mechanisms involved in female-specific cancers which support tumor growth in a different manner. Integrated computational approaches may allow us to better detect genomic similarities between these different female-specific cancers, helping us to deliver more sophisticated diagnosis and precise treatments. Recently, several initiatives of The Cancer Genome Atlas (TCGA) have encouraged integrated analyses of multiple cancers rather than individual tumors. These studies revealed common genetic alterations (driver genes) even in clinically distinct entities such as breast, ovarian, and endometrial cancers. In this study, we aimed to identify expression similarity signatures by extracting common genes among TCGA breast (BRCA), ovarian (OV), and uterine corpus endometrial carcinoma (UCEC) cohorts and infer co-regulatory protein–protein interaction networks that might have a relationship with the estrogen signaling pathway. Thus, we carried out an unsupervised principal component analysis (PCA)-based computational approach, using RNA sequencing data of 2,015 female cancer and 148 normal samples, in order to simultaneously capture the data heterogeneity of intertumors. Firstly, we identified tumor-associated genes from gene expression profiles. Secondly, we investigated the signaling pathways and co-regulatory protein–protein interaction networks underlying these three cancers by leveraging the Ingenuity Pathway Analysis software. In detail, we discovered 1,643 expression similarity signatures (638 downregulated and 1,005 upregulated genes, with respect to normal phenotype), denoted as tumor-associated genes. Through functional genomic analyses, we assessed that these genes were involved in the regulation of cell-cycle-dependent mechanisms, including metaphase kinetochore formation and estrogen-dependent S-phase entry. Furthermore, we generated putative co-regulatory protein–protein interaction networks, based on upstream regulators such as the ERBB2/HER2 gene. Moreover, we provided an ad-hoc bioinformatics workflow with a manageable list of intertumor expression similarity signatures for the three female-specific cancers. The expression similarity signatures identified in this study might uncover potential estrogen-dependent molecular mechanisms promoting carcinogenesis. Frontiers Media S.A. 2020-12-03 /pmc/articles/PMC7793872/ /pubmed/33424936 http://dx.doi.org/10.3389/fgene.2020.612521 Text en Copyright © 2020 Pane, Affinito, Zanfardino, Castaldo, Incoronato, Salvatore and Franzese. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Pane, Katia
Affinito, Ornella
Zanfardino, Mario
Castaldo, Rossana
Incoronato, Mariarosaria
Salvatore, Marco
Franzese, Monica
An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title_full An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title_fullStr An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title_full_unstemmed An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title_short An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
title_sort integrative computational approach based on expression similarity signatures to identify protein–protein interaction networks in female-specific cancers
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793872/
https://www.ncbi.nlm.nih.gov/pubmed/33424936
http://dx.doi.org/10.3389/fgene.2020.612521
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