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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353400/ https://www.ncbi.nlm.nih.gov/pubmed/34365093 http://dx.doi.org/10.1016/j.ebiom.2021.103510 |
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author | Li, Yin Xu, Fengkai Chen, Fanghua Chen, Yiwei Ge, Di Zhang, Shu Lu, Chunlai |
author_facet | Li, Yin Xu, Fengkai Chen, Fanghua Chen, Yiwei Ge, Di Zhang, Shu Lu, Chunlai |
author_sort | Li, Yin |
collection | PubMed |
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. TNS1(high) 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 TNS1(high) 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. |
format | Online Article Text |
id | pubmed-8353400 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-83534002021-08-15 Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma Li, Yin Xu, Fengkai Chen, Fanghua Chen, Yiwei Ge, Di Zhang, Shu Lu, Chunlai EBioMedicine Research paper 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. TNS1(high) 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 TNS1(high) 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. Elsevier 2021-08-05 /pmc/articles/PMC8353400/ /pubmed/34365093 http://dx.doi.org/10.1016/j.ebiom.2021.103510 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research paper Li, Yin Xu, Fengkai Chen, Fanghua Chen, Yiwei Ge, Di Zhang, Shu Lu, Chunlai Transcriptomics based multi-dimensional characterization and drug screen in esophageal squamous cell carcinoma |
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 | Research paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353400/ https://www.ncbi.nlm.nih.gov/pubmed/34365093 http://dx.doi.org/10.1016/j.ebiom.2021.103510 |
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