Dataset Information

Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma.

ABSTRACT:

Background

To identify potential key genes predicting unfavorable prognosis in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).

Methods

Gene expression profiles of GSE121248, GSE62232, and GSE55092 from the GEO database were obtained and analyzed. Differentially expressed genes (DEGs) between HBV-associated HCC tissues and adjacent normal tissues were screened by the limma package and Venn diagram software. Functional assessment of DEGs was performed by Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Hub genes were selected by the protein-protein interaction (PPI) network and further validated by GSE14520 clinical data.

Results

A total of 26 up-regulated genes and 76 down-regulated genes were identified by analyzing three databases. GO and KEGG analysis demonstrated that these genes were involved in cell division, metabolism-related biological processes, the p53 pathway, and the cell cycle, among others. PPI network suggested that 14 hub DEGs (TOP2A, HMMR, DTL, CCNB1, NEK2, PBK, RACGAP1, PRC1, CDK1, RRM2, ECT2, BUB1B, ANLN, and ASPM) were most dysregulated and had potential to distinguish between HBV-associated HCC and noncancerous tissues. Further survival analysis of hub genes demonstrated that high expression of TOP2A was significantly associated with poor clinical outcomes of HBV-associated HCC.

Conclusions

TOP2A might serve as a key gene for prognosis and as a therapeutic target for HBV-associated HCC.

SUBMITTER: Sha M

PROVIDER: S-EPMC8267317 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma.

Sha Meng M Cao Jie J Zong Zhi-Peng ZP Xu Ning N Zhang Jian-Jun JJ Tong Ying Y Xia Qiang Q

Annals of translational medicine 20210601 12

<h4>Background</h4>To identify potential key genes predicting unfavorable prognosis in hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC).<h4>Methods</h4>Gene expression profiles of GSE121248, GSE62232, and GSE55092 from the GEO database were obtained and analyzed. Differentially expressed genes (DEGs) between HBV-associated HCC tissues and adjacent normal tissues were screened by the limma package and Venn diagram software. Functional assessment of DEGs was performed by Gene Onto ...[more]

PMID: 34277775

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Project description:BackgroundExtensive evidence links Clonorchis sinensis (C. sinensis) to cholangiocarcinoma; however, its association with hepatocellular carcinoma (HCC) is less acknowledged, and the underlying mechanism remains unclear. This study was designed to investigate the association between C. sinensis infection and HCC and reveal the relationship between C. sinensis infection and cancer stemness.MethodsA comprehensive analysis of 839 HCC patients categorized into C. sinensis (-) HCC and C. sinensis (+) HCC groups was conducted. Chi-square and Mann-Whitney U tests were used to assess the association between C. sinensis infection and clinical factors. Kaplan-Meier and Cox regression analyses were used to evaluate survival outcomes. Immunohistochemistry was used to determine CK19 and EpCAM expression in HCC specimens.ResultsCompared to C. sinensis (-) HCC patients, C. sinensis (+) HCC patients exhibited advanced Barcelona Clinic Liver Cancer (BCLC) stage, higher male prevalence and more liver cirrhosis as well as elevated alpha-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), eosinophil, complement 3 (C3), and complement 4 (C4) values. C. sinensis infection correlated with shorter overall survival (OS) (p < 0.05) and recurrence-free survival (RFS) (p < 0.05). Furthermore, Cox multivariate analysis revealed that C. sinensis infection was an independent prognostic factor for OS in HCC patients. Importantly, C. sinensis infection upregulated the expression of HCC cancer stem cell markers CK19 and EpCAM.ConclusionHCC patients with C. sinensis infection exhibit a poor prognosis following hepatectomy. Moreover, C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC.Author summaryClonorchis sinensis (C. sinensis) is a prominent food-borne parasite prevalent in regions such as China, particularly in Guangxi. C. sinensis has been associated with various hepatobiliary system injuries, encompassing inflammation, periductal fibrosis, cholangiocarcinoma and even hepatocellular carcinoma (HCC). A substantial body of evidence links C. sinensis to cholangiocarcinoma, However, the connection between C. sinensis and HCC and the intricate mechanisms underlying its contribution to HCC development remain incompletely elucidated. Our study demonstrates clear clinicopathological associations between C. sinensis and HCC, such as gender, BCLC stage, liver cirrhosis, MVI, AFP, CA19-9, circulating eosinophils and complements. Furthermore, we found that the co-occurrence of C. sinensis exhibited a significant association with shorter OS and RFS in patients diagnosed with HCC. A major finding was that C. sinensis infection promotes the acquisition of cancer stem cell-like characteristics, consequently accelerating the malignant progression of HCC. Our results provide a more comprehensive comprehension of the interplay between C. sinensis and HCC, shedding fresh light on the carcinogenic potential of C. sinensis.

Project description:Hepatocellular carcinoma (HCC) is a common malignant cancer with poor survival outcomes, and hepatitis B virus (HBV) infection is most likely to contribute to HCC. But the molecular mechanism remains obscure. Our study intended to identify the candidate potential hub genes associated with the carcinogenesis of HBV-related HCC (HBV-HCC), which may be helpful in developing novel tumor biomarkers for potential targeted therapies. Four transcriptome datasets (GSE84402, GSE25097, GSE94660, and GSE121248) were used to screen the 309 overlapping differentially expressed genes (DEGs), including 100 upregulated genes and 209 downregulated genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to explore the biological function of DEGs. A PPI network based on the STRING database was constructed and visualized by the Cytoscape software, consisting of 209 nodes and 1676 edges. Then, we recognized 17 hub genes by CytoHubba plugin, which were further validated on additional three datasets (GSE14520, TCGA-LIHC, and ICGC-LIRI-JP). The diagnostic effectiveness of hub genes was assessed with receiver operating characteristic (ROC) analysis, and all hub genes displayed good performance in discriminating TNM stage I patient samples and normal tissue ones. For prognostic analysis, two prognostic key genes (TOP2A and KIF11) out of the 17 hub genes were screened and used to develop a prognostic signature, which showed good potential for overall survival (OS) stratification of HBV-HCC patients. Gene Set Enrichment Analysis (GSEA) was performed in order to better understand the function of this prognostic gene signature. Finally, the miRNA-mRNA regulatory relationships of all hub genes in human liver were predicted using miRNet. In conclusion, the current study gives further insight on the pathogenesis and carcinogenesis of HBV-HCC, and the identified DEGs provide a promising direction for improving the diagnostic, prognostic, and therapeutic outcomes of HBV-HCC.

Dataset Information

Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma.

Background

Methods

Results

Conclusions

Publications

Identification of genes predicting unfavorable prognosis in hepatitis B virus-associated hepatocellular carcinoma.

Similar Datasets

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