Browsing by Issue Date, starting with "2019-03-12"
Now showing 1 - 2 of 2
Results Per Page
Sort Options
- Epigenetic biomarkers as predictors of clinical outcomes in colorectal cancerPublication . Ramalhete, Sara Maria Ventura; Castelo-Branco, PedroColorectal Cancer is the third most common cancer and the second leading cause of death by cancer worldwide with about 1.3 million new cancer cases and 693,933 deaths reported in 2012. Here, we intend to determine an epigenetic roadmap of Colorectal Cancer to predict tumor progression and patient outcome. We analyzed whole-genome DNA methylation (Illumina Infinium HumanMethylation 450K array) and gene expression (Illumina HiSeq) in multiple stages of CRC (21 normal, 54 stage I, 131 stage II, 111 stage III, and 51 stage IV). The data is available in TCGA database, and was downloaded, processed and analyzed through R programming. Results show that, in stages I, II, III, and IV, 307, 400, 305 and 233 genes are differentially expressed (fold-change absolute value > 1.5, p-value adjusted<0.05) and 924, 1814, 1169, and 618 CpG sites are differentially methylated (Δβ absolute value > 0.2, p-value adjusted<0.05), respectively. In addition, all these CpG sites are correlated with the respective gene. When the KEGG and Gene Ontology analysis was performed, we found that the enriched functions are related to nervous system, one of the processes deregulated in cancer progression. Moreover, we also identified 66, 85, 41, and 40 specific genes for stages I, II, III, and IV, respectively. Regarding the diagnosis, were found 238 genes and 835 CpG sites as good diagnosis tool for stage I (AUC>0.8). Furthermore, 6, 1, and 5 genes and 87, 7, and 3 CpG sites were classified as good biomarkers for overall survival for stages I-IV, respectively. In addition, 3, 3, and 2 genes and 30, 12, 9 CpG sites were identified as good biomarkers for recurrence free survival for stages I-IV, respectively. These results suggest that different methylation events are associated to specific stages of CRC which can predict patient outcome and might improve colorectal cancer diagnosis and prognosis.
- Roadmap of DNA methylation in breast cancer identifies novel prognostic biomarkersPublication . Almeida, Bernardo; Apolónio, Joana; Binnie, Alexandra; Castelo-Branco, PedroBackground Breast cancer is a highly heterogeneous disease resulting in diverse clinical behaviours and therapeutic responses. DNA methylation is a major epigenetic alteration that is commonly perturbed in cancers. The aim of this study is to characterize the relationship between DNA methylation and aberrant gene expression in breast cancer. Methods We analysed DNA methylation and gene expression profiles from breast cancer tissue and matched normal tissue in The Cancer Genome Atlas (TCGA). Genome-wide differential methylation analysis and methylation-gene expression correlation was performed. Gene expression changes were subsequently validated in the METABRIC dataset. The Oncoscore tool was used to identify genes that had previously been associated with cancer in the literature. A subset of genes that had not previously been studied in cancer was chosen for further analysis. Results We identified 368 CpGs that were differentially methylated between tumor and normal breast tissue (∆β > 0.4). Hypermethylated CpGs were overrepresented in tumor tissue and were found predominantly (56%) in upstream promoter regions. Conversely, hypomethylated CpG sites were found primarily in the gene body (66%). Expression analysis revealed that 209 of the differentially-methylated CpGs were located in 169 genes that were differently expressed between normal and breast tumor tissue. Methylation-expression correlations were predominantly negative (70%) for promoter CpG sites and positive (74%) for gene body CpG sites. Among these differentially-methylated and differentially-expressed genes, we identified 7 that had not previously been studied in any form of cancer. Three of these, TDRD10, PRAC2 and TMEM132C, contained CpG sites that showed diagnostic and prognostic value in breast cancer, particularly in estrogen-receptor (ER)-positive samples. A pan-cancer analysis confirmed differential expression of these genes together with diagnostic and prognostic value of their respective CpG sites in multiple cancer types. Conclusion We have identified 368 DNA methylation changes that characterize breast cancer tumor tissue, of which 209 are associated with genes that are differentially-expressed in the same samples. Novel DNA methylation markers were identified, of which cg12374721 (PRAC2), cg18081940 (TDRD10) and cg04475027 (TMEM132C) show promise as diagnostic and prognostic markers in breast cancer as well as other cancer types.