Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma

IntroductionEsophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied.MethodsIn this study, we investigate the genomic and transcriptomic characteristics and try to provide the...

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Main Authors: Xiaqin Zhang, Jianhong Lian, Fukun Chen, Kai Wang, Haoyuan Xue, Sufang Jia, Weili Wang, Zhongkang Li, Hua Liang, Hongwei Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1495200/full
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author Xiaqin Zhang
Jianhong Lian
Fukun Chen
Kai Wang
Haoyuan Xue
Sufang Jia
Weili Wang
Zhongkang Li
Hua Liang
Hongwei Li
author_facet Xiaqin Zhang
Jianhong Lian
Fukun Chen
Kai Wang
Haoyuan Xue
Sufang Jia
Weili Wang
Zhongkang Li
Hua Liang
Hongwei Li
author_sort Xiaqin Zhang
collection DOAJ
description IntroductionEsophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied.MethodsIn this study, we investigate the genomic and transcriptomic characteristics and try to provide the basic T-cell receptors (TCRs) dynamics and its genomic and transcriptome association during the radiochemotherapy of ESCC using multi-omics analysis.ResultsA total of 23 patients with pathologic diagnoses of locally advanced ESCC were enrolled. The median tumor mutational burden (TMB) of the 23 ESCC patients were 3.47 mutations/ Mb (mega-base). The TP53, RTK/RAS, and NOTCH pathways were concurrently prevalent in ESCC. Besides, some less prevalent pathways, including WNT and HIPPO pathways also exhibited superior frequencies in ESCC. Meantime, we found the immune-hot tumor had higher immune infiltration scores. The median TMB in the progression-free survival (PFS) low group was significantly higher than that in the PFS-high group. The chromosomal copy number variation (CNV) burden of the neutrophil-to-lymphocyte ratio (NLR)-high group appeared to be higher than that of the NLR-low group, and the StromalScore in the NLR-low group was significantly higher. Clonality score was significantly increased from pre-treat to post-treat and from on-treat to post-treat. Shannon index was significantly decreased from pre-treat to post-treat and from on-treat to posttreat. Richness was significantly decreased from pre-treat to post-treat.DiscussionMultiomics analysis provided the basic TCRs dynamics and their genomic and transcriptome association during the radio-chemotherapy of 23 locally advanced ESCC in China, and provided a valuable insights into the heterogeneity and the tumor microenvironment and treatment responses. Meantimes, the identification of biomarkers and the exploration of their association with treatment outcomes could have important implications for clinical practice.
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spelling doaj-art-76d21bae9ee341a8a67bfed8c13862192025-01-06T06:59:12ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-01-011410.3389/fonc.2024.14952001495200Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinomaXiaqin Zhang0Jianhong Lian1Fukun Chen2Kai Wang3Haoyuan Xue4Sufang Jia5Weili Wang6Zhongkang Li7Hua Liang8Hongwei Li9Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Thoracic Surgery, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaGeneplus-Beijing, Beijing, ChinaGeneplus-Beijing, Beijing, ChinaShanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaGeneplus-Beijing, Beijing, ChinaLudwig Center for Metastasis Research, Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, United StatesDepartment of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, ChinaIntroductionEsophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied.MethodsIn this study, we investigate the genomic and transcriptomic characteristics and try to provide the basic T-cell receptors (TCRs) dynamics and its genomic and transcriptome association during the radiochemotherapy of ESCC using multi-omics analysis.ResultsA total of 23 patients with pathologic diagnoses of locally advanced ESCC were enrolled. The median tumor mutational burden (TMB) of the 23 ESCC patients were 3.47 mutations/ Mb (mega-base). The TP53, RTK/RAS, and NOTCH pathways were concurrently prevalent in ESCC. Besides, some less prevalent pathways, including WNT and HIPPO pathways also exhibited superior frequencies in ESCC. Meantime, we found the immune-hot tumor had higher immune infiltration scores. The median TMB in the progression-free survival (PFS) low group was significantly higher than that in the PFS-high group. The chromosomal copy number variation (CNV) burden of the neutrophil-to-lymphocyte ratio (NLR)-high group appeared to be higher than that of the NLR-low group, and the StromalScore in the NLR-low group was significantly higher. Clonality score was significantly increased from pre-treat to post-treat and from on-treat to post-treat. Shannon index was significantly decreased from pre-treat to post-treat and from on-treat to posttreat. Richness was significantly decreased from pre-treat to post-treat.DiscussionMultiomics analysis provided the basic TCRs dynamics and their genomic and transcriptome association during the radio-chemotherapy of 23 locally advanced ESCC in China, and provided a valuable insights into the heterogeneity and the tumor microenvironment and treatment responses. Meantimes, the identification of biomarkers and the exploration of their association with treatment outcomes could have important implications for clinical practice.https://www.frontiersin.org/articles/10.3389/fonc.2024.1495200/fullesophageal squamous cell carcinomatranscriptomeT-cell receptor analysisradiotherapymulti-omics analysis esophageal squamous cell carcinomamulti-omics analysis
spellingShingle Xiaqin Zhang
Jianhong Lian
Fukun Chen
Kai Wang
Haoyuan Xue
Sufang Jia
Weili Wang
Zhongkang Li
Hua Liang
Hongwei Li
Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
Frontiers in Oncology
esophageal squamous cell carcinoma
transcriptome
T-cell receptor analysis
radiotherapy
multi-omics analysis esophageal squamous cell carcinoma
multi-omics analysis
title Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
title_full Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
title_fullStr Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
title_full_unstemmed Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
title_short Genomic, transcriptomic, and T cell receptor profiling in stratifying response to first-line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
title_sort genomic transcriptomic and t cell receptor profiling in stratifying response to first line chemoradiotherapy or radiotherapy for esophageal squamous cell carcinoma
topic esophageal squamous cell carcinoma
transcriptome
T-cell receptor analysis
radiotherapy
multi-omics analysis esophageal squamous cell carcinoma
multi-omics analysis
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1495200/full
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