Dataset Information

Pathway Analysis of Genes Identified through Post-GWAS to Underpin Prostate Cancer Aetiology.

ABSTRACT: Understanding the functional role of risk regions identified by genome-wide association studies (GWAS) has made considerable recent progress and is referred to as the post-GWAS era. Annotation of functional variants to the genes, including cis or trans and understanding their biological pathway/gene network enrichments, is expected to give rich dividends by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS data that is validated through further studies in prostate cancer, to investigate molecular biological pathways enriched for assigned functional genes. In total, about 100 canonical pathways were significantly, at false discovery rate (FDR)< 0.05), enriched in assigned genes using different algorithms. The results have highlighted some well-known cancer signalling pathways, antigen presentation processes and enrichment in cell growth and development gene networks, suggesting risk loci may exert their functional effect on prostate cancer by acting through multiple gene sets and pathways. Additional upstream analysis of the involved genes identified critical transcription factors such as HDAC1 and STAT5A. We also investigated the common genes between post-GWAS and three well-annotated gene expression datasets to endeavour to uncover the main genes involved in prostate cancer development/progression. Post-GWAS generated knowledge of gene networks and pathways, although continuously evolving, if analysed further and targeted appropriately, will have an important impact on clinical management of the disease.

SUBMITTER: Farashi S

PROVIDER: S-EPMC7291227 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Pathway Analysis of Genes Identified through Post-GWAS to Underpin Prostate Cancer Aetiology.

Farashi Samaneh S Kryza Thomas T Batra Jyotsna J

Genes 20200508 5

Understanding the functional role of risk regions identified by genome-wide association studies (GWAS) has made considerable recent progress and is referred to as the post-GWAS era. Annotation of functional variants to the genes, including <i>cis</i> or <i>trans</i> and understanding their biological pathway/gene network enrichments, is expected to give rich dividends by elucidating the mechanisms underlying prostate cancer. To this aim, we compiled and analysed currently available post-GWAS dat ...[more]

PMID: 32397189

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Project description:Gene co-expression networks (GCNs) have been developed as relevant analytical tools for the study of the gene expression patterns behind complex phenotypes. Determining the association between structure and function in GCNs is a current challenge in biomedical research. Several structural differences between GCNs of breast cancer and healthy phenotypes have been reported. In a previous study, using co-expression multilayer networks, we have shown that there are abrupt differences in the connectivity patterns of the GCN of basal-like breast cancer between top co-expressed gene-pairs and the remaining gene-pairs. Here, we compared the top-100,000 interactions networks for the four breast cancer phenotypes (Luminal-A, Luminal-B, Her2+ and Basal), in terms of structural properties. For this purpose, we used the graph-theoretical k-core of a network (maximal sub-network with nodes of degree at least k). We developed a comprehensive analysis of the network k-core ([Formula: see text]) structures in cancer, and its relationship with biological functions. We found that in the Top-100,000-edges networks, the majority of interactions in breast cancer networks are intra-chromosome, meanwhile inter-chromosome interactions serve as connecting bridges between clusters. Moreover, core genes in the healthy network are strongly associated with processes such as metabolism and cell cycle. In breast cancer, only the core of Luminal A is related to those processes, and genes in its core are over-expressed. The intersection of the core nodes in all subtypes of cancer is composed only by genes in the chr8q24.3 region. This region has been observed to be highly amplified in several cancers before, and its appearance in the intersection of the four breast cancer k-cores, may suggest that local co-expression is a conserved phenomenon in cancer. Considering the many intricacies associated with these phenomena and the vast amount of research in epigenomic regulation which is currently undergoing, there is a need for further research on the epigenomic effects on the structure and function of gene co-expression networks in cancer.

Dataset Information

Pathway Analysis of Genes Identified through Post-GWAS to Underpin Prostate Cancer Aetiology.

Publications

Pathway Analysis of Genes Identified through Post-GWAS to Underpin Prostate Cancer Aetiology.

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