Integrative single-cell multiomics analyses dissect molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer
Shuhui Bian,Yicheng Wang,Yuxuan Zhou,Wendong Wang,Limei Guo,Lu Wen,Wei Fu,Xin Zhou,Fuchou Tang +8 more
TL;DR: In this paper , the authors performed multi-regional sampling, parallel single-cell multi-omics sequencing and integrated analyses of human gastric cancer, and revealed the singlecell DNA methylome landscape of Gastric cancer and identified candidate DNA methylation biomarkers, such as hypermethylated promoters of TMEM240 and HAGLROS.
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Abstract: Abstract Human gastric cancer is a highly lethal disease, but the underlying multiomic molecular signatures remain largely unclear. Here, we performed multi-regional sampling, parallel single-cell multiomics sequencing and integrated analyses of human gastric cancer. We identified common transcriptomic alterations of gastric cancer cells, such as aberrant down-regulation of genes associated with normal stomach function and up-regulation of KRT7, PI3, S100A4, etc. Surprisingly, aberrant and prevalent up-regulation of genes highly expressed in normal colorectal epithelial cells were also identified in cancer cells, which may be partially regulated by promoter chromatin accessibility and DNA methylation levels. We revealed the single-cell DNA methylome landscape of gastric cancer, and identified candidate DNA methylation biomarkers, such as hypermethylated promoters of TMEM240 and HAGLROS, and hypomethylated promoters of TRPM2-AS and HRH1. Additionally, the relationships between genetic lineages, DNA methylation and transcriptomic clusters were systematically revealed at single-cell level. We showed that DNA methylation heterogeneities were mainly among different genetic lineages of cancer cells. Moreover, we found that DNA methylation levels of cancer cells with poorer differentiation states tend to be higher than those of cancer cells with better differentiation states in the primary tumor within the same patient, although still lower than in normal gastric epithelial cells. Cancer cells with poorer differentiation states also prevalently down-regulated MUC1 expression and immune-related pathways, and had poor infiltration of CD8+ T cells. Our study dissected the molecular signatures of intratumoral heterogeneities and differentiation states of human gastric cancer using integrative single-cell multiomics analyses.
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Citations
DeepSF-4mC: A deep learning model for predicting DNA cytosine 4mC methylation sites leveraging sequence features
Fei Li,Jiaming Chen,Jiezhang Wu,Ying Zhan,Xiaodan Wu,Zhiguo Wang,Guoxu Zhang +6 more
TL;DR: DeepSF-4mC is proposed, a deep learning model specifically designed for predicting DNA cytosine 4mC methylation sites by leveraging sequence features that incorporates multiple encoding techniques to enhance prediction accuracy, increase model stability, and reduce the computational resources needed.
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TL;DR: HAGLROS promotes the growth of PTC by competitively binding to miR-206 to promote HMGA2 expression and repressed PTC tumor growth in mice.
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TL;DR: A comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project is described and a molecular classification dividing gastric cancer into four subtypes is proposed.
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