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Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation
OBJECTIVE: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorl...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419897/ https://www.ncbi.nlm.nih.gov/pubmed/34488754 http://dx.doi.org/10.1186/s12935-021-02171-9 |
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author | Qiu, Hu Song, Haixia Luo, Man Ke, Shaobo Shi, Wei Chen, Jiamei Zhao, Wensi Luo, Hesheng Chen, Yongshun |
author_facet | Qiu, Hu Song, Haixia Luo, Man Ke, Shaobo Shi, Wei Chen, Jiamei Zhao, Wensi Luo, Hesheng Chen, Yongshun |
author_sort | Qiu, Hu |
collection | PubMed |
description | OBJECTIVE: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. METHODS: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC. RESULTS: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence. CONCLUSION: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer. |
format | Online Article Text |
id | pubmed-8419897 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84198972021-09-09 Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation Qiu, Hu Song, Haixia Luo, Man Ke, Shaobo Shi, Wei Chen, Jiamei Zhao, Wensi Luo, Hesheng Chen, Yongshun Cancer Cell Int Primary Research OBJECTIVE: Definitive chemoradiotherapy (dCRT) is one of the standard treatments for esophageal squamous cell carcinoma (ESCC), but local recurrence is the main cause of treatment failure. The changes in apoptosis and autophagy in recurrent tumors of patients with ESCC following dCRT have been poorly estimated. Thus, this study aimed to investigate the expressions of key regulators of apoptosis and autophagy in matched paired samples of primary and recurrent ESCC. METHODS: The medical records of patients with locally advanced ESCC who developed local recurrence after dCRT were reviewed, and the expression profiling of apoptosis-related genes, cell apoptosis, autophagy and autophagy-related proteins were detected in normal esophageal squamous epithelium and paired samples of primary and recurrent ESCC. RESULTS: A total of 126 patients were enrolled, and 52.4% of them had stage III disease. The 1-, 3- and 5-year local recurrence-free survival (LRFS) rates were 54.8, 19.8 and 14.3%, respectively, with a median LRFS of 13.0 months. Patients with T2 tumor or stage II disease showed a significantly prolonged LRFS compared with that of patients with T3-4 tumor or stage III disease. The Apoptotic Machinery key genes expression profiling identified 5 upregulated and 7 downregulated apoptosis-related genes in recurrent tumors compared with their expression levels in the matched primary ESCC tumors. High expression of CD40, TRAF4 and BCL2A1, and low expression of CARD6 and TNFRSF21 were associated with increased risk of early local recurrence after dCRT. No differences in apoptotic index between primary and recurrent samples were detected. However, typical morphological features of autophagosomes and elevated LC3-II protein expression were detected in recurrent tumor samples, and positive LC3-II expression was correlated with increased risk of early local recurrence. CONCLUSION: Our findings indicated that apoptosis and autophagy dysfunction correlated with early local recurrence in patients with locally advanced ESCC receiving dCRT. Further studies are necessary to understand the biology of tumor recurrence in esophageal cancer. BioMed Central 2021-09-06 /pmc/articles/PMC8419897/ /pubmed/34488754 http://dx.doi.org/10.1186/s12935-021-02171-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Qiu, Hu Song, Haixia Luo, Man Ke, Shaobo Shi, Wei Chen, Jiamei Zhao, Wensi Luo, Hesheng Chen, Yongshun Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title | Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title_full | Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title_fullStr | Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title_full_unstemmed | Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title_short | Dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
title_sort | dysfunction of apoptosis and autophagy correlates with local recurrence in esophageal squamous cell carcinoma after definitive chemoradiation |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419897/ https://www.ncbi.nlm.nih.gov/pubmed/34488754 http://dx.doi.org/10.1186/s12935-021-02171-9 |
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