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Comprehensive analysis of gene expression profiles to identify differential prognostic factors of primary and metastatic breast cancer |
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| Institution: | Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia |
| Abstract: | Breast cancer accounts for nearly half of all cancer-related deaths in women worldwide. However, the molecular mechanisms that lead to tumour development and progression remain poorly understood and there is a need to identify candidate genes associated with primary and metastatic breast cancer progression and prognosis. In this study, candidate genes associated with prognosis of primary and metastatic breast cancer were explored through a novel bioinformatics approach. Primary and metastatic breast cancer tissues and adjacent normal breast tissues were evaluated to identify biomarkers characteristic of primary and metastatic breast cancer. The Cancer Genome Atlas-breast invasive carcinoma (TCGA-BRCA) dataset (ID: HS-01619) was downloaded using the mRNASeq platform. Genevestigator 8.3.2 was used to analyse TCGA-BRCA gene expression profiles between the sample groups and identify the differentially-expressed genes (DEGs) in each group. For each group, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to determine the function of DEGs. Networks of protein–protein interactions were constructed to identify the top hub genes with the highest degree of interaction. Additionally, the top hub genes were validated based on overall survival and immunohistochemistry using The Human Protein Atlas. Of the top 20 hub genes identified, four (KRT14, KIT, RAD51, and TTK) were considered as prognostic risk factors based on overall survival. KRT14 and KIT expression levels were upregulated while those of RAD51 and TTK were downregulated in patients with breast cancer. The four proposed candidate hub genes might aid in further understanding the molecular changes that distinguish primary breast tumours from metastatic tumours as well as help in developing novel therapeutics. Furthermore, they may serve as effective prognostic risk markers based on the strong correlation between their expression and patient overall survival. |
| Keywords: | Breast cancer Metastasis Prognostic marker Overall survival Differentially expressed genes Protein-protein interaction BC"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"breast cancer BP"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"biological process CC"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"cellular component CI"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"confidence interval DEG"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"differentially expressed gene FDR"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"false discovery rate GEPIA"} {"#name":"keyword" "$":{"id":"k0100"} "$$":[{"#name":"text" "_":"gene expression profiling interactive analysis GO"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"gene ontology HR"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"hazard ratio IDC"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"infiltrating ductal carcinoma KEGG"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"Kyoto Encyclopedia of Genes and Genomes MCODE"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"molecular complex detection MF"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"molecular function OS"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"overall survival PPI"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"protein-protein interaction RNA-Seq"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"RNA sequencing STRING"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"search tool for the retrieval of interacting genes TCGA-BRCA"} {"#name":"keyword" "$":{"id":"k0210"} "$$":[{"#name":"text" "_":"The Cancer Genome Atlas-breast invasive carcinoma |
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