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Prognostic value of Nrf2/HO-1 expression and its correlation with occurrence in esophageal squamous cell carcinoma

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Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is thought to be started and developed by genes associated with inflammation. A cancer's ability to spread and grow can be aided by nuclear factor erythroid-2 related factor 2 (Nrf2) hyperactivation, which can also make a tumor more resistant to chemotherapy and radiation treatment. However, it is still unknown how Nrf2 gene expression affects ESCC prognosis and controls function throughout ESCC advancement.

Objective

The expression of Nrf2 and HO-1 in ESCC and precancerous esophageal precancerous lesions was analyzed, and their relationship with esophageal squamous cell carcinoma was analyzed.

Methods

Immunohistochemistry (IHC) was used to confirm the expression of Nrf2 and heme oxygenase-1 (HO-1) proteins in tissue microarrays from Chinese populations with ESCC. We looked at the connections between Nrf2/HO-1 expression and invading immune cells using the TIMER database.

Results

Ethnicity and N stage are associated with Nrf2 overexpression. Differentiation, N stage, vascular invasion, distant metastasis, and American Joint Committee on Cancer (AJCC) staging are all associated with HO-1 overexpression. The expression of Nrf2 and HO-1 had a favorable correlation. Patients with elevated Nrf2 and HO-1 expression had lower progression-free survival (PFS) and overall survival (OS). In high-grade intraepithelial neoplasia, Nrf2 and HO-1 expression generally occurred, partially in low-grade intraepithelial neoplasia specimens, and rarely in normal mucosa. We further show that Nrf2 suppression is linked to higher immunological marker expression and lower immune cell infiltration.

Conclusion

The prognosis of ESCC may be improved by inhibiting the expression of Nrf2 and HO-1. A lack of immune cells was seen in ESCC with Nrf2 impairment.

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Data Availability

Data is available on request from the authors.

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (No. 81860422) and Xinjiang Uygur Autonomous Region graduate innovation project (CXCY2022010). Many thanks go to the members of the research team for the careful guidance and technical support.

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Author notes

  1. Yongmei Gao

    Present address: Xinjiang Medical University, Urumqi, Xinjiang, China

Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China

    Yongmei Gao, Mengyan Li & Yuqing Ma

  2. Xinjiang Medical University, Urumqi, Xinjiang, China

    Bo Wang

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  1. Yongmei Gao
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Correspondence to Yuqing Ma.

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Author Yongmei Gao, author Mengyan Li, author Bo Wang, and author Yuqing Ma declare that they have no conflict of interest.

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This study had been approved by the Ethics Committee of First Affiliated Hospital of Xinjiang Medical University. Informed from all individual participants included in the study.

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Gao, Y., Li, M., Wang, B. et al. Prognostic value of Nrf2/HO-1 expression and its correlation with occurrence in esophageal squamous cell carcinoma. Genes Genom 45, 723–739 (2023). https://doi.org/10.1007/s13258-023-01371-z

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  • DOI: https://doi.org/10.1007/s13258-023-01371-z

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