Identification of enhancer RNA AC005515.1 as a novel biomarker for prognosis in esophageal cancer and predictors of immunotherapy response

Lihua Jia; Jianghua Chen; Jia Zhao; Junbao Yang

doi:10.21037/tcr-23-777

Identification of enhancer RNA AC005515.1 as a novel biomarker for prognosis in esophageal cancer and predictors of immunotherapy response

Transl Cancer Res. 2023 Dec 31;12(12):3266-3283. doi: 10.21037/tcr-23-777. Epub 2023 Dec 15.

Authors

Lihua Jia¹, Jianghua Chen¹, Jia Zhao², Junbao Yang^{1

3}

Affiliations

¹ Institute of Basic Medicine and Forensic Medicine, North Sichuan Medical College and Center for Genetics and Prenatal Diagnosis, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
² Department of Medical Laboratory, Nanchong Central Hospital, Nanchong, China.
³ Department of Clinical Genetics, School of Medical Laboratory, North Sichuan Medical College, Nanchong, China.

Abstract

Background: The enhancer RNA (eRNA) signature shows excellent promise in the prognostic role of many malignancies, but its value has not been fully explored in esophageal cancer (ESCA).

Methods: We comprehensively analyzed 33 oncogene expression matrices and clinical data from The Cancer Genome Atlas (TCGA) and identified ESCA prognostic-related key eRNAs by Kaplan-Meier and co-expression analysis. We also investigated the prognostic role of the key eRNA using a series of bioinformatics approaches, including immune infiltration, immune function, immune subtypes, and the tumor microenvironment. Finally, the tumor immune dysfunction and exclusion (TIDE) score was used to predict the immune response to immune checkpoint blockade (ICB) therapy.

Results: We identified eRNA AC005515.1, AC012368.1, AP003469.2, Clorf61, and WDFY3-AS2 were associated with the prognosis of ESCA. AC005515.1 is a critical prognostic-related eRNA in ESCA and was significantly co-expressed with immune checkpoint genes (CTLA4, CD274, etc.). In the pan-cancer analysis, AC005515.1 was also associated with the prognosis of seven cancers, including kidney renal papillary cell carcinoma and low-grade brain glioma. It was also found to be co-expressed with immune checkpoint genes in these tumors. Moreover, high expression of AC005515.1 was associated with CD8⁺ T cells and M1 macrophages infiltration, and the AC005515.1 high-expression group had a higher TIDE score in ESCA.

Conclusions: Overall, eRNA AC005515.1 is associated with the local immune environment of ESCA and may become a new biomarker of ESCA prognosis and immunotherapy response.

Keywords: AC005515.1; Esophageal cancer (ESCA); enhancer RNA (eRNA); immune checkpoint; pan-cancer analysis.