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Published on: April 12, 2024
An Inflammation-Associated Prognosis Model for Hepatocellular Carcinoma Based on Adenylate Uridylate- (AU-) Rich
Li Song1, Xiangzheng Su2, Yao Lu2
1Academy of Advanced Interdisciplinary Studies, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China.
Insights
This study identifies five inflammation-associated adenylate uridylate- (AU-) rich element genes (AREGs) that can predict hepatocellular carcinoma (HCC) outcomes. This novel signature may improve prognostic accuracy for HCC patients.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Hepatocellular carcinoma (HCC) is a major inflammation-driven cancer globally.
- The role of adenylate uridylate- (AU-) rich element genes (AREGs) in HCC pathogenesis is not well understood.
Purpose of the Study:
- To identify differentially expressed AREGs (DE-AREGs) in HCC.
- To develop and validate an AREG-based prognostic signature for HCC.
- To explore the biological and immune-related significance of the signature.
Main Methods:
- Utilized TCGA and GEO databases for HCC datasets.
- Identified DE-AREGs and performed univariate Cox and LASSO regression for prognostic gene selection.
- Constructed a prognostic signature and nomogram, validated with functional, pathway, and immune infiltration analyses.
- Verified gene expression via RT-qPCR.
Main Results:
- Identified 189 DE-AREGs; selected CENPA, TXNRD1, RABIF, UGT2B15, and SERPINE1 for the prognostic signature.
- The signature demonstrated prognostic accuracy and correlated with various biological functions and pathways.
- Significant differences in immune cell infiltration (T cells, B cells) and endothelial cells were observed between risk groups.
Conclusions:
- An inflammation-associated signature comprising five DE-AREGs was successfully constructed for HCC.
- This signature serves as a potential prognostic indicator for hepatocellular carcinoma patients.
Abstract:
Hepatocellular carcinoma (HCC) is a typical inflammation-driven cancer and ranks sixth in the incidence rate worldwide. The role of adenylate uridylate- (AU-) rich element genes (AREGs) in HCC remains unclear. HCC-related datasets were acquired from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Differentially expressed AREGs (DE-AREGs) between HCC samples and healthy controls were identified. The univariate Cox and LASSO analyses were performed to determine the prognostic genes. Furthermore, a signature and corresponding nomogram were configured for the clinical prediction of HCC. The potential signature-related biological significance was explored using functional and pathway enrichment analysis. Additionally, immune infiltration analysis was also performed. Finally, the expression of prognostic genes was verified using real-time quantitative polymerase chain reaction (RT-qPCR). A total of 189 DE-AREGs between normal and HCC samples were identified, wherein CENPA, TXNRD1, RABIF, UGT2B15, and SERPINE1 were selected to generate an AREG-related signature. Moreover, the prognostic accuracy of the AREG-related signature was also confirmed. Functional analysis indicated that the high-risk score was related to various functions and pathways. Inflammation and immune-related analyses indicated that the difference of T cell and B cell receptor abundance, microvascular endothelial cells (MVE), lymphatic endothelial cells (lye), pericytes, stromal cells, and the six immune checkpoints was statistically significant between the different risk groups. Similarly, RT-qPCR outcomes of these signature genes were also significant. In conclusion, an inflammation-associated signature based on five DE-AREGs was constructed, which could act as a prognostic indicator of patients with HCC.
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