Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value
The tumor heterogeneity of the transcriptional profiles is independent of genetic variation. Several studies have successfully identified esophageal squamous cell carcinoma (ESCC) subtypes based on the somatic mutation profile and copy number variations on the genome. However, transcriptome-based cl...
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1033214/full |
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| author | Danke Wang Jiacheng Dai Chen Suo Chen Suo Chen Suo Shangzi Wang Yuting Zhang Xingdong Chen Xingdong Chen Xingdong Chen Xingdong Chen |
| author_facet | Danke Wang Jiacheng Dai Chen Suo Chen Suo Chen Suo Shangzi Wang Yuting Zhang Xingdong Chen Xingdong Chen Xingdong Chen Xingdong Chen |
| author_sort | Danke Wang |
| collection | DOAJ |
| description | The tumor heterogeneity of the transcriptional profiles is independent of genetic variation. Several studies have successfully identified esophageal squamous cell carcinoma (ESCC) subtypes based on the somatic mutation profile and copy number variations on the genome. However, transcriptome-based classification is limited. In this study, we classified 141 patients with ESCC into three subtypes (Subtype 1, Subtype 2, and Subtype 3) via tumor sample gene expression profiling. Differential gene expression (DGE) analysis of paired tumor and normal samples for each subtype revealed significant difference among subtypes. Moreover, the degree of change in the expression levels of most genes gradually increased from Subtype 1 to Subtype 3. Gene set enrichment analysis (GSEA) identified the representative pathways in each subtype: Subtype 1, abnormal Wnt signaling pathway activation; Subtype 2, inhibition of glycogen metabolism; and Subtype 3, downregulation of neutrophil degranulation process. Weighted gene co-expression network analysis (WGCNA) was used to elucidate the finer regulation of biological pathways and discover hub genes. Subsequently, nine hub genes (CORO1A, CD180, SASH3, CD52, CD300A, CD14, DUSP1, KIF14, and MCM2) were validated to be associated with survival in ESCC based on the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database. The clustering analysis of ESCC granted better understanding of the molecular characteristics of ESCC and led to the discover of new potential therapeutic targets that may contribute to the clinical treatment of ESCC. |
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| issn | 1664-8021 |
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| last_indexed | 2024-04-11T07:12:57Z |
| publishDate | 2022-11-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-0317d3dd85a44b16964a4dfddbebd57e2022-12-22T04:38:05ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10332141033214Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic valueDanke Wang0Jiacheng Dai1Chen Suo2Chen Suo3Chen Suo4Shangzi Wang5Yuting Zhang6Xingdong Chen7Xingdong Chen8Xingdong Chen9Xingdong Chen10State Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, ChinaFudan University Taizhou Institute of Health Sciences, Taizhou, ChinaDepartment of Epidemiology, School of Public Health, Fudan University, Shanghai, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, ChinaState Key Laboratory of Genetic Engineering, Human Phenome Institute, School of Life Sciences, Fudan University, Shanghai, ChinaFudan University Taizhou Institute of Health Sciences, Taizhou, ChinaDepartment of Neurology, Huashan Hospital, Fudan University, Shanghai, ChinaYiwu Research Institute of Fudan University, Yiwu, Zhejiang, ChinaThe tumor heterogeneity of the transcriptional profiles is independent of genetic variation. Several studies have successfully identified esophageal squamous cell carcinoma (ESCC) subtypes based on the somatic mutation profile and copy number variations on the genome. However, transcriptome-based classification is limited. In this study, we classified 141 patients with ESCC into three subtypes (Subtype 1, Subtype 2, and Subtype 3) via tumor sample gene expression profiling. Differential gene expression (DGE) analysis of paired tumor and normal samples for each subtype revealed significant difference among subtypes. Moreover, the degree of change in the expression levels of most genes gradually increased from Subtype 1 to Subtype 3. Gene set enrichment analysis (GSEA) identified the representative pathways in each subtype: Subtype 1, abnormal Wnt signaling pathway activation; Subtype 2, inhibition of glycogen metabolism; and Subtype 3, downregulation of neutrophil degranulation process. Weighted gene co-expression network analysis (WGCNA) was used to elucidate the finer regulation of biological pathways and discover hub genes. Subsequently, nine hub genes (CORO1A, CD180, SASH3, CD52, CD300A, CD14, DUSP1, KIF14, and MCM2) were validated to be associated with survival in ESCC based on the RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) database. The clustering analysis of ESCC granted better understanding of the molecular characteristics of ESCC and led to the discover of new potential therapeutic targets that may contribute to the clinical treatment of ESCC.https://www.frontiersin.org/articles/10.3389/fgene.2022.1033214/fullESCCgene expression profilesubtypeintegrateGSEAWGCNA |
| spellingShingle | Danke Wang Jiacheng Dai Chen Suo Chen Suo Chen Suo Shangzi Wang Yuting Zhang Xingdong Chen Xingdong Chen Xingdong Chen Xingdong Chen Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value Frontiers in Genetics ESCC gene expression profile subtype integrate GSEA WGCNA |
| title | Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value |
| title_full | Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value |
| title_fullStr | Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value |
| title_full_unstemmed | Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value |
| title_short | Molecular subtyping of esophageal squamous cell carcinoma by large-scale transcriptional profiling: Characterization, therapeutic targets, and prognostic value |
| title_sort | molecular subtyping of esophageal squamous cell carcinoma by large scale transcriptional profiling characterization therapeutic targets and prognostic value |
| topic | ESCC gene expression profile subtype integrate GSEA WGCNA |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1033214/full |
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