Towards the DNA methylation haplotype map of 11 common solid cancers
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ABSTRACT:
PROVIDER: PRJNA875426 | ENA |
REPOSITORIES: ENA
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Project description:Aberrant DNA methylation is an epigenetic hallmark of cancer, known to play an essential role in cancer initiation, progression and drug resistance. Traditional analyses focus on mean methylation that measures the aggregated signal across a group of cells and neglect intra-sample heterogeneity. Sequencing-based techniques such as whole genome bisulfite sequencing (WGBS) are now widely used to measure DNA methylation on each read at single-nucleotide resolution. A single read fragment stems from a single chromosome of a single cell and represents a DNA methylation haplotype (mHap). In this study, we have profiled 110 fresh frozen tumor samples that cover 11 most common solid cancer types using WGBS and constructed a comprehensive DNA methylation haplotype map.
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Project description:BackgroundA stronger spatial clustering of cancer burden indicates stronger environmental and human behavioral effects. However, which common cancers in China have stronger spatial clustering and knowledge gaps regarding the environmental and human behavioral effects have yet to be investigated. This study aimed to compare the spatial clustering degree and hotspot patterns of 11 common cancers in mainland China and discuss the potential environmental and behavioral risks underlying the patterns.MethodsCancer incidence data recorded at 339 registries in 2014 was obtained from the "China Cancer Registry Annual Report 2017". We calculated the spatial clustering degree of the common cancers using the global Moran's Index and identified the hotspot patterns using the hotspot analysis.ResultsWe found that esophagus, stomach and liver cancer have a significantly higher spatial clustering degree ([Formula: see text]) than others. When by sex, female esophagus, male stomach, male esophagus, male liver and female lung cancer had significantly higher spatial clustering degree ([Formula: see text]). The spatial clustering degree of male liver was significantly higher than that of female liver cancer ([Formula: see text]), whereas the spatial clustering degree of female lung was significantly higher than that of male lung cancer ([Formula: see text]). The high-risk areas of esophagus and stomach cancer were mainly in North China, Huai River Basin, Yangtze River Delta and Shaanxi Province. The hotspots for liver and male liver cancer were mainly in Southeast China and south Hunan. Hotspots of female lung cancer were mainly located in the Pearl River Delta, Shandong, North and Northeast China. The Yangtze River Delta and the Pearl River Delta were high-risk areas for multiple cancers.ConclusionsThe top highly clustered cancer types in mainland China included esophagus, stomach and liver cancer and, by sex, female esophagus, male stomach, male esophagus, male liver and female lung cancer. Among them, knowledge of their spatial patterns and environmental and behavioral risk factors is generally limited. Potential factors such as unhealthy diets, water pollution and climate factors have been suggested, and further investigation and validation are urgently needed, particularly for male liver cancer. This study identified the knowledge gap in understanding the spatial pattern of cancer burdens in China and offered insights into targeted cancer monitoring and control.
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Project description:Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types, into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO (GSE42284, GSE10893, and GSE26712 for the colon, breast, and ovarian samples, respectively). Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers. A total of 338 samples were analyzed.
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