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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Gastrointestinal Cancers: Gastric and Esophageal Cancers
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1495200

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

Provisionally accepted
Xiaqin Zhang Xiaqin Zhang 1*Jianhong Lian Jianhong Lian 1*Fukun Chen Fukun Chen 2Wang Kai Wang Kai 2Haoyuan Xue Haoyuan Xue 3*Sufang Jia Sufang Jia 1*Weili Wang Weili Wang 1Zhongkang Li Zhongkang Li 2Hua Liang Hua Liang 4*Hongwei Li Hongwei Li 1*
  • 1 Shanxi Provincial Cancer Hospital, Taiyuan, China
  • 2 Geneplus Beijing Institute, Huilongguan Town, Beijing, China
  • 3 Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 4 The University of Chicago, Chicago, Illinois, United States

The final, formatted version of the article will be published soon.

    Esophageal squamous cell carcinoma (ESCC) accounts for 80% of esophageal cancer (EC) worldwide. The molecular characteristics of locally advanced ESCC have been extensively studied. In 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 radio-chemotherapy of ESCC using multi-omics analysis. A 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 post-treat.Richness was significantly decreased from pre-treat to post-treat. Multi-omics 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 4 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.

    Keywords: esophageal squamous cell carcinoma, Transcriptome, T-cell receptor analysis, Radiotherapy, Multi-omics analysis Esophageal squamous cell carcinoma, Multi-omics analysis

    Received: 12 Sep 2024; Accepted: 26 Nov 2024.

    Copyright: © 2024 Zhang, Lian, Chen, Kai, Xue, Jia, Wang, Li, Liang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiaqin Zhang, Shanxi Provincial Cancer Hospital, Taiyuan, China
    Jianhong Lian, Shanxi Provincial Cancer Hospital, Taiyuan, China
    Haoyuan Xue, Shanxi Medical University, Taiyuan, 030001, Shanxi Province, China
    Sufang Jia, Shanxi Provincial Cancer Hospital, Taiyuan, China
    Hua Liang, The University of Chicago, Chicago, 60637, Illinois, United States
    Hongwei Li, Shanxi Provincial Cancer Hospital, Taiyuan, China

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