TY - JOUR
T1 - An Integrative Computational Approach Based on Expression Similarity Signatures to Identify Protein–Protein Interaction Networks in Female-Specific Cancers
AU - Pane, Katia
AU - Affinito, Ornella
AU - Zanfardino, Mario
AU - Castaldo, Rossana
AU - Incoronato, Mariarosaria
AU - Salvatore, Marco
AU - Franzese, Monica
N1 - Funding Information:
This work was supported by Progetti di Ricerca Corrente funded by the Italian Ministry of Health.
Publisher Copyright:
© Copyright © 2020 Pane, Affinito, Zanfardino, Castaldo, Incoronato, Salvatore and Franzese.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/3
Y1 - 2020/12/3
N2 - 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.
AB - 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.
KW - bioinformatics
KW - breast cancer
KW - endometrial cancer
KW - molecular signatures
KW - ovarian cancer
KW - principal component analysis - PCA
KW - signaling pathway
KW - TCGA
UR - http://www.scopus.com/inward/record.url?scp=85097761142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097761142&partnerID=8YFLogxK
U2 - 10.3389/fgene.2020.612521
DO - 10.3389/fgene.2020.612521
M3 - Article
AN - SCOPUS:85097761142
VL - 11
JO - Frontiers in Genetics
JF - Frontiers in Genetics
SN - 1664-8021
M1 - 612521
ER -