Exploration of Sorafenib Influences on Gene Expression of Hepatocellular Carcinoma
1First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
Purpose:
The aim of this study was to develop a comprehensive differential gene profile for hepatocellular carcinoma (HCC) patients treated with sorafenib.
Methods:
The RNA sequencing data and miRNA sequencing data of 114 HCC patients treated with sorafenib only and 326 HCC control patients treated without any chemotherapeutic drugs were studied using differential expression, functional enrichment, and protein-protein interaction analysis.
Results:
Compared with HCC patients without any chemotherapy drugs, the sorafenib-treated patients develop 66 differentially expressed genes (DEGs), including 12 upregulated genes and 54 downregulated genes. Additionally, three differentially expressed miRNAs (DEMs) also show specific expression pattern. With further analysis, five primary genes including HTR2C, TRH, AGTR2, MCHR2, and SLC6A2 as well as three miRNAs (hsa-miR-4445, hsa-miR-466, and hsa-miR-2114) have been suggested as the potential targets for sorafenib. The specific gene expression of five genes has been validated in clinical HCC patients by ELISA method. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses indicate several significantly enriched biological processes (BPs), cellular components (CCs), and molecular functions (MFs).
Conclusion:
Since sorafenib is becoming increasingly important in HCC treatment clinically, this study will help us understand the potential targets and eliminate diverse existing side effects of it as well as explore several potential clinical biomarkers with comprehensive analysis of differential gene expression profile.
Insights
This study identifies key gene expression changes in hepatocellular carcinoma (HCC) patients treated with sorafenib. These findings offer insights into sorafenib
Area of Science:
- Oncology
- Genomics
- Pharmacogenomics
Background:
- Hepatocellular carcinoma (HCC) is a significant global health concern.
- Sorafenib is a crucial targeted therapy for advanced HCC.
- Understanding the molecular mechanisms of sorafenib is vital for optimizing treatment.
Purpose of the Study:
- To establish a comprehensive differential gene expression profile for HCC patients undergoing sorafenib treatment.
- To identify potential molecular targets and biomarkers associated with sorafenib efficacy and side effects in HCC.
Main Methods:
- RNA and miRNA sequencing data from 114 sorafenib-treated HCC patients and 326 untreated controls were analyzed.
- Differential expression analysis, functional enrichment (GO, KEGG), and protein-protein interaction analyses were performed.
- Key gene and miRNA candidates were validated using ELISA in clinical HCC samples.
Main Results:
- 66 differentially expressed genes (DEGs) and 3 differentially expressed miRNAs (DEMs) were identified in sorafenib-treated HCC patients.
- Five genes (HTR2C, TRH, AGTR2, MCHR2, SLC6A2) and three miRNAs (hsa-miR-4445, hsa-miR-466, hsa-miR-2114) were proposed as potential sorafenib targets.
- Functional enrichment analysis revealed significant biological processes, cellular components, and molecular functions affected by sorafenib.
Conclusions:
- The identified differential gene expression profile provides a deeper understanding of sorafenib's action in HCC.
- This research highlights potential therapeutic targets and clinical biomarkers for sorafenib in HCC treatment.
- Findings may aid in mitigating sorafenib's side effects and improving patient outcomes.
More Related Videos
09:32Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
Published on: October 17, 2025
12:24A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Related Concept Videos
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
mTOR Signaling and Cancer Progression
The mTOR pathway or the...
Cell Specific Gene Expression
Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
Hepatic Drug Excretion: Influencing Factors
Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
