TMB Signature-Related RCAN2 Promotes Apoptosis by Upregulating EHF/DR5 Pathway in Hepatocellular Carcinoma
Yu-Jie Xu1, Zhi-Cheng Lai2,3, Anna Kan2,3
1Department of Hepatobiliary Pancreatic Surgery, Guangzhou First People's Hospital, 510000 Guangzhou, Guangdong, China.
Frontiers in Bioscience (Landmark Edition)
|July 31, 2024
Summary
RCAN2 downregulation correlates with high tumor mutation burden (TMB) in cancers. In hepatocellular carcinoma (HCC), increased RCAN2 promotes apoptosis via the EHF/DR5 pathway, offering new treatment strategies.
Area of Science:
- Oncology
- Genomics
- Molecular Biology
Background:
- Tumor mutation burden (TMB) is linked to tumor behavior and prognosis, but underlying genetic mechanisms remain unclear.
- Identifying genes associated with TMB is crucial for understanding tumor biology and developing targeted therapies.
Purpose of the Study:
- To identify key genes associated with TMB in hepatocellular carcinoma (HCC).
- To investigate the biological functions, downstream factors, and mechanisms of TMB-related genes in HCC.
Main Methods:
- Analysis of The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database to classify patients by TMB signature-related genes.
- Identification of key prognostic genes using immunohistochemistry and qPCR.
- In vitro and in vivo studies to assess the impact of gene expression on cell proliferation and apoptosis.
- Utilizing databases and sequencing data to elucidate mechanisms and downstream transcription factors.
Main Results:
- A TMB signature-related gene group (IC2) showed significantly different TMB scores and better prognosis.
- Five key prognostic genes were identified, with RCAN2 negatively correlated with TMB in 18 tumor types.
- High RCAN2 expression correlated with better HCC survival, enhanced apoptosis, and involved the EHF/DR5 pathway.
Conclusions:
- RCAN2 downregulation is associated with elevated TMB across multiple cancer types.
- RCAN2 serves as a prognostic biomarker in HCC and promotes apoptosis through the EHF/DR5 pathway.
- These findings offer novel insights for systemic treatment of advanced HCC with high TMB.
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