Identification of diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus‑associated early stage hepatocellular carcinoma based on RNA‑sequencing data

Abstract

Primary liver cancer is a rapidly progressing neoplasm with high morbidity and mortality rates. The present study aimed to identify potential diagnostic and prognostic biomarkers, and candidate targeted agents for hepatitis B virus (HBV)-associated early stage hepatocellular carcinoma (HCC). The gene expression profiles were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs), hub genes and the enrichment of signaling pathways were filtered out via a high-throughput sequencing method. The association between hub genes and the effects of the abnormal expression of hub genes on the rate of genetic variation, overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS) and disease-free survival (DSS) of patients with HCC, as well as pathological stage and grade, were analyzed using different databases. A total of 1,582 DEGs were identified. Gene Ontology analysis revealed that the DEGs were mainly involved in the 'oxidation-reduction process', 'steroid metabolic process', 'metabolic process' and 'fatty acid beta-oxidation'. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways revealed that the DEGs were mainly associated with 'metabolic pathways', 'PPAR signaling pathway', 'fatty acid degradation' and the 'cell cycle'. A total of 8 hub genes were extracted. Additionally, the abnormal expression levels of hub genes were closely associated with the OS, RFS, PFS and DSS of patients, the pathological stage and the grade. Furthermore, abnormal expression levels of the 8 hub genes were found in >30% of all samples. Several small molecular compounds that may reverse the altered DEGs were identified based on Connectivity Map analysis, including phenoxybenzamine, GW-8510, resveratrol, 0175029-0000 and daunorubicin. In conclusion, the dysfunction of fat metabolic pathways, the cell cycle, oxidation-reduction processes and viral carcinogenesis may serve critical roles in the occurrence of HBV-associated early stage HCC. The identified 8 hub genes may act as robust biomarkers for diagnosis and prognosis. Some small molecular compounds may be promising targeted agents against HBV-associated early stage HCC.

Detection of reproducible liver cancer specific ligand-receptor signaling in blood

“…Figure 1B; Suppl. File 1) (Jiang et al, 2019; Zeng et al, 2020). Consistent with a prior observation (Villemin et al, 2023), a greater number of LRIs were detected in scRNA-seq data, with bulk RNA-sequencing contributing a modest number of unique LRIs (Suppl.…”

“…A count matrix of bulk RNA-seq dataset of CHB HCC tissue samples (Jiang et al, 2019; Zeng et al, 2020) was downloaded from GEO under the ascension number GSE124535. The count matrix contained FPKM values of 35 HCC liver tissue samples and was used to infer LRIs with the R package BulkSignalR as described with the parameter “normalize=FALSE” in the “prepareDataset” function.…”

“…Additionally, more than 60% of liver cancer patients had chronic hepatitis B (CHB) infection (Chen et al, 2022). Zeng et al, 2020) In order to infer LRIs, the count matrices were separately (per biological condition) prepared for subsequent analysis using the function "prepareDataset" from the R (version 4.1.2) (R Core Team, 2021) package BulkSignalR (version 0.0.9) (Villemin et al, 2023). Next, the function "learnParameters" from the package BulkSignalR was employed to estimate the statistical model parameters and finally, with the function "initialInference" from the package BulkSignalR LRIs are inferred and stored in a BSRInference object.…”

Recent Research Progress in Chinese Alternative Medicine in the Prevention and Treatment of Liver Cancer

“…Through connectivity map analysis, several small molecule compounds were identified that might reverse the changes in DEGs, including benzoxybenzylamine, GW-8510, resveratrol, 0175029-0000, and rosiglitazone. Considering the critical role that dysfunctions in fatty metabolism pathways, cell cycle, oxidation-reduction processes, and viral carcinogenesis may play in the development of HBV-related early HCC, the study proposed that the identified eight hub genes (CDC20, CCNB1, AURKB, CCNA2, CDK1, APOA1, UBB, EHHADH) could serve as potent biomarkers and therapeutic targets for diagnosis and prognosis [31].…”

Identification of a Potential PPAR-Related Multigene Signature Predicting Prognosis of Patients with Hepatocellular Carcinoma

“…Numerous studies have revealed that tumorigenesis and cancer progression are usually accompanied by abnormal regulation of the PPAR signaling pathway [9][10][11][12]. In addition, in recent studies on HCC prognostic markers, it has been repeatedly reported that the PPAR signaling pathway is dysregulated in highrisk HCC patients with poor prognosis [13][14][15]. Although the PPAR signaling pathway has been reported as one of the prognostic characteristic pathways of HCC, no one has screened the prognostic markers for HCC from the genes involved in this pathway.…”