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Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a critical innate immune pathway that could virtually impact nearly all aspects of tumorigenesis including colorectal cancer. This work aimed to develop and validate molecular subtypes related to cGAS-ST...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290593/ https://www.ncbi.nlm.nih.gov/pubmed/37355491 http://dx.doi.org/10.1007/s10142-023-01102-3 |
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author | Zhang, Jiawei Wu, Yangsheng Shen, Zhong |
author_facet | Zhang, Jiawei Wu, Yangsheng Shen, Zhong |
author_sort | Zhang, Jiawei |
collection | PubMed |
description | The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a critical innate immune pathway that could virtually impact nearly all aspects of tumorigenesis including colorectal cancer. This work aimed to develop and validate molecular subtypes related to cGAS-STING pathways for colorectal cancer using Bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data. Bulk RNA-seq data were acquired from The Cancer Genome Atlas dataset (training dataset) and Gene Expression Omnibus dataset (validation dataset). Univariate COX survival analysis was utilized to identify prognostic differentially expressed genes (DEGs) from 6 immune pathways related to cGAS-STING. ConsensusClusterPlus package was used to classify different subtypes based on DEGs. scRNA-seq data were used to validate differences in immune status between different subtypes. Two clusters with distinct prognosis were identified based on 27 DEGs. The six cGAS-STING-related pathways had different levels of significance between the two clusters. Clust1 had most number of amplified CNVs and clust2 had the most number of loss CNVs. TP53 was the top mutated gene of which missense mutations contributed the most of single-nucleotide variants. Immune score of clust1 was higher than that in clust2, as reflected in macrophages, T cells, and natural killer cells. Three unfavorable genes and 31 protection factors were screened between the two clusters in three datasets. ScRNA-seq data analysis demonstrated that macrophages were more enriched in clust1, and tumor cells and immune cells had close interaction. We classified two distinct subtypes with different prognosis, mutation landscape, and immune characteristics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10142-023-01102-3. |
format | Online Article Text |
id | pubmed-10290593 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-102905932023-06-26 Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer Zhang, Jiawei Wu, Yangsheng Shen, Zhong Funct Integr Genomics Original Article The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway has emerged as a critical innate immune pathway that could virtually impact nearly all aspects of tumorigenesis including colorectal cancer. This work aimed to develop and validate molecular subtypes related to cGAS-STING pathways for colorectal cancer using Bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data. Bulk RNA-seq data were acquired from The Cancer Genome Atlas dataset (training dataset) and Gene Expression Omnibus dataset (validation dataset). Univariate COX survival analysis was utilized to identify prognostic differentially expressed genes (DEGs) from 6 immune pathways related to cGAS-STING. ConsensusClusterPlus package was used to classify different subtypes based on DEGs. scRNA-seq data were used to validate differences in immune status between different subtypes. Two clusters with distinct prognosis were identified based on 27 DEGs. The six cGAS-STING-related pathways had different levels of significance between the two clusters. Clust1 had most number of amplified CNVs and clust2 had the most number of loss CNVs. TP53 was the top mutated gene of which missense mutations contributed the most of single-nucleotide variants. Immune score of clust1 was higher than that in clust2, as reflected in macrophages, T cells, and natural killer cells. Three unfavorable genes and 31 protection factors were screened between the two clusters in three datasets. ScRNA-seq data analysis demonstrated that macrophages were more enriched in clust1, and tumor cells and immune cells had close interaction. We classified two distinct subtypes with different prognosis, mutation landscape, and immune characteristics. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10142-023-01102-3. Springer Berlin Heidelberg 2023-06-24 2023 /pmc/articles/PMC10290593/ /pubmed/37355491 http://dx.doi.org/10.1007/s10142-023-01102-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Zhang, Jiawei Wu, Yangsheng Shen, Zhong Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title | Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title_full | Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title_fullStr | Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title_full_unstemmed | Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title_short | Integration of bulk RNA sequencing data and single-cell RNA sequencing analysis on the heterogeneity in patients with colorectal cancer |
title_sort | integration of bulk rna sequencing data and single-cell rna sequencing analysis on the heterogeneity in patients with colorectal cancer |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10290593/ https://www.ncbi.nlm.nih.gov/pubmed/37355491 http://dx.doi.org/10.1007/s10142-023-01102-3 |
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