Research Paper Volume 16, Issue 3 pp 2232—2248
Identification of an immune-related eRNA prognostic signature for clear cell renal cell carcinoma
- 1 Department of Urology, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 215228, China
- 2 Central Laboratory, First Affiliated Hospital, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116021, China
- 3 Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
- 4 Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, China
- 5 Department of Urology, The State Key Lab of Reproductive, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- 6 Department of Urology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
- 7 Department of Clinical Laboratory, Children’s Hospital of Nanjing Medical University, Nanjing, China
Received: August 15, 2023 Accepted: December 1, 2023 Published: January 29, 2024
https://doi.org/10.18632/aging.205479How to Cite
Copyright: © 2024 Lv et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Immune-related enhancer RNAs (eRNAs) have garnered significant attention in cancer metabolism research, yet their specific roles in ccRCC have remained elusive.
Methods: We retrieved eRNA expression profiles from TCGA database and identified immune-related eRNAs (IREs) by assessing their co-expression with immune genes. Utilizing consensus clustering, we organized these IREs into two distinct clusters. The construction of an IREs signature was accomplished through the LASSO and multivariate Cox analysis. Furthermore, we performed Cell Counting Kit-8 and clonogenic assays to assess changes in the proliferative capacity of Caki-1 and 769-P cells.
Results: The existence of two clusters of immune-related eRNAs in ccRCC, each with distinctive prognostic and immunological attributes. Cluster B exhibited immunosuppressive properties and displayed a positive correlation with immunosuppressive cells. Functional enrichment analysis unveiled their involvement in several tumor-promoting pathways, metabolic pathways and immune pathways. The IREs signature demonstrated its potential to accurately predict patient immune and prognostic characteristics. AC003092.1, an eRNA strongly associated with patient survival, emerged as a potential oncogene significantly linked to adverse prognosis and the presence of immunosuppressive cells and checkpoints in ccRCC patients. Notably, AC003092.1 displayed marked upregulation in ccRCC tissues and cell lines, and its knockdown substantially inhibited the proliferation of Caki-1 and 769-P cells.
Conclusion: We established a robust predictive model that played a vital role in determining the prognosis, clinicopathological characteristics and immune cell infiltration patterns of ccRCC patients. IRE, particularly AC003092.1, which was strongly associated with survival, hold promise as novel immunotherapeutic targets for ccRCC.