Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma
Background: Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Methods: Expression profiles of multiple ESCC datasets were...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396421003030 |
| _version_ | 1818887077839765504 |
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| author | Yin Li Fengkai Xu Fanghua Chen Yiwei Chen Di Ge Shu Zhang Chunlai Lu |
| author_facet | Yin Li Fengkai Xu Fanghua Chen Yiwei Chen Di Ge Shu Zhang Chunlai Lu |
| author_sort | Yin Li |
| collection | DOAJ |
| description | Background: Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Methods: Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. Findings: The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Interpretation: Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1high fibroblasts in TME, and identified potential drugs for clinical use. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section. |
| first_indexed | 2024-12-19T16:31:30Z |
| format | Article |
| id | doaj.art-277c75d860544d4682cf274dc7618678 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-19T16:31:30Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-277c75d860544d4682cf274dc76186782022-12-21T20:14:10ZengElsevierEBioMedicine2352-39642021-08-0170103510Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinomaYin Li0Fengkai Xu1Fanghua Chen2Yiwei Chen3Di Ge4Shu Zhang5Chunlai Lu6Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaLiver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, ChinaLiver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion (Ministry of Education), Fudan University, Shanghai, China; Institutes of Biomedical Sciences, Fudan University, Shanghai, China; Corresponding authors.Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China; Corresponding authors.Background: Esophageal squamous cell carcinoma (ESCC) remains one of the deadly cancer types. Comprehensively dissecting the molecular characterization and the heterogeneity of ESCC paves the way for developing more promising therapeutics. Methods: Expression profiles of multiple ESCC datasets were integrated. ATAC-seq and RNA-seq were combined to reveal the chromatin accessibility features. A prognosis-related subtype classifier (PrSC) was constructed, and its association with the tumor microenvironment (TME) and immunotherapy was assessed. The key gene signature was validated in clinical samples. Based on the TME heterogeneity of ESCC patients, potential subtype-specific therapeutic agents were screened. Findings: The common differentially expressed genes (cDEGs) in ESCC were identified. Up-regulated genes (HEATR1, TIMELESS, DTL, GINS1, RUVBL1, and ECT2) were found highly important in ESCC cell survival. The expression alterations of PRIM2, HPGD, NELL2, and TFAP2B were associated with chromatin accessibility changes. PrSC was a robust scoring tool that was not only associated with the prognosis of ESCC patients, but also could reflect the TME heterogeneity. TNS1high fibroblasts were associated with immune exclusion. TG-101348 and Vinorelbine were identified as potential subtype-specific therapeutic agents. Besides, the application of PrSC into two immunotherapy cohorts indicated its potential value in assessing treatment response to immunotherapy. Interpretation: Our study depicted the multi-dimensional characterization of ESCC, established a robust scoring tool for the prognosis assessment, highlighted the role of TNS1high fibroblasts in TME, and identified potential drugs for clinical use. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.http://www.sciencedirect.com/science/article/pii/S2352396421003030Esophageal squamous cell carcinomaRNA-seqATAC-seqMolecular classificationTumor stromaDrug repurposing |
| spellingShingle | Yin Li Fengkai Xu Fanghua Chen Yiwei Chen Di Ge Shu Zhang Chunlai Lu Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma EBioMedicine Esophageal squamous cell carcinoma RNA-seq ATAC-seq Molecular classification Tumor stroma Drug repurposing |
| title | Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| title_full | Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| title_fullStr | Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| title_full_unstemmed | Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| title_short | Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| title_sort | transcriptomics based multi dimensional characterization and drug screen in esophageal squamous cell carcinoma |
| topic | Esophageal squamous cell carcinoma RNA-seq ATAC-seq Molecular classification Tumor stroma Drug repurposing |
| url | http://www.sciencedirect.com/science/article/pii/S2352396421003030 |
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