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Exploration of Sorafenib Influences on Gene Expression of Hepatocellular Carcinoma.

ABSTRACT: 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.

SUBMITTER: Wang H

PROVIDER: S-EPMC7578401 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exploration of Sorafenib Influences on Gene Expression of Hepatocellular Carcinoma.

Wang Huancheng H Liu Jia J

Frontiers in genetics 20201008

<h4>Purpose</h4>The aim of this study was to develop a comprehensive differential gene profile for hepatocellular carcinoma (HCC) patients treated with sorafenib.<h4>Methods</h4>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.<h4>Results</h4>Compared with HCC patients w ...[more]

PMID: 33133165

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Project description:BackgroundPhase III trials show sorafenib improves survival in advanced hepatocellular carcinoma (HCC). Because of narrow trial eligibility, results may not be generalizable to a broader HCC population. We sought to evaluate the effectiveness of initial sorafenib versus no treatment among Medicare beneficiaries with advanced HCC.Materials and methodsPatients with advanced HCC diagnosed from 2008 to 2011 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Eligible patients received initial sorafenib or no therapy and were covered by Medicare parts A, B, and D. Sorafenib use and outcomes were described in this population. Using a propensity score (PS)-matched sample, we compared the effectiveness of sorafenib versus no treatment by Cox proportional hazards and binomial regression, using a landmark requiring all patients to survive ?60 days after diagnosis.ResultsOf 1,532 patients, 27% received initial sorafenib. Median duration of sorafenib use was 60 days (interquartile range [IQR], 30-107 days), and median survival from first prescription was 3 months (IQR, 1-8 months). In the PS-matched cohort, median survival was 3 months from the 60-day landmark in sorafenib-treated (n = 223) and 2 months in untreated (n = 223) patients (adjusted hazard ratio, 0.95 [95% confidence interval (CI), 0.78-1.16]). Sorafenib was associated with a nonsignificant reduction in mortality at 3 months (44% versus 51%; adjusted risk ratio, 0.88 [95% CI, 0.72-1.07]), but no reduction thereafter.ConclusionSurvival after sorafenib initiation in newly diagnosed Medicare beneficiaries with HCC is exceptionally short, suggesting trial results are not generalizable to all HCC patients. The downsides of sorafenib use-high drug-related symptom burden and high drug cost-must be considered in light of this minimal benefit.Implications for practiceThe findings of a median survival of only 3 months in Medicare beneficiaries with HCC prescribed sorafenib as first-line therapy highlight the questionable value of sorafenib in this population. Patients should be cautioned that outside of the narrow confines of randomized trials, their life expectancy may be very short, and any benefit of sorafenib is likely to be quite small. Given that sorafenib causes considerable adverse effects and offers no symptom palliation, supportive care should be discussed as a reasonable alternative to sorafenib, particularly for patients who have a poor performance status or advanced cirrhosis.

Dataset Information

Exploration of Sorafenib Influences on Gene Expression of Hepatocellular Carcinoma.

Publications

Exploration of Sorafenib Influences on Gene Expression of Hepatocellular Carcinoma.

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