Dataset Information

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication.

ABSTRACT:

Background

Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer death with a poor prognosis. However, the underlying molecular mechanisms are largely unclear, and effective treatment for it is limited. Using an integrated bioinformatics method, the present study aimed to identify the key candidate prognostic genes that are involved in HCC development and identify small-molecule drugs with treatment potential.

Methods and results

In this study, by using three expression profile datasets from Gene Expression Omnibus database, 1,704 differentially expressed genes were identified, including 671 upregulated and 1,033 downregulated genes. Then, weighted co-expression network analysis revealed nine modules are related with pathological stage; turquoise module was the most associated module. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway analyses (KEGG) indicated that these genes were enriched in cell division, cell cycle, and metabolic related pathways. Furthermore, by analyzing the turquoise module, 22 genes were identified as hub genes. Based on HCC data from gene expression profiling interactive analysis (GEPIA) database, nine genes associated with progression and prognosis of HCC were screened, including ANLN, BIRC5, BUB1B, CDC20, CDCA5, CDK1, NCAPG, NEK2, and TOP2A. According to the Human Protein Atlas and the Oncomine database, these genes were highly upregulated in HCC tumor samples. Moreover, multivariate Cox regression analysis showed that the risk score based on the gene expression signature of these nine genes was an independent prognostic factor for overall survival and disease-free survival in HCC patients. In addition, the candidate small-molecule drugs for HCC were identified by the CMap database.

Conclusion

In conclusion, the nine key gene signatures related to HCC progression and prognosis were identified and validated. The cell cycle pathway was the core pathway enriched with these key genes. Moreover, several candidate molecule drugs were identified, providing insights into novel therapeutic approaches for HCC.

SUBMITTER: Jiang N

PROVIDER: S-EPMC7940693 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication.

Jiang Nan N Zhang Xinzhuo X Qin Dalian D Yang Jing J Wu Anguo A Wang Long L Sun Yueshan Y Li Hong H Shen Xin X Lin Jing J Kantawong Fahsai F Wu Jianming J

Frontiers in genetics 20210223

<h4>Background</h4>Hepatocellular carcinoma (HCC) is one of the most leading causes of cancer death with a poor prognosis. However, the underlying molecular mechanisms are largely unclear, and effective treatment for it is limited. Using an integrated bioinformatics method, the present study aimed to identify the key candidate prognostic genes that are involved in HCC development and identify small-molecule drugs with treatment potential.<h4>Methods and results</h4>In this study, by using three ...[more]

PMID: 33708237

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Project description:BackgroundHepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. The average survival and 5-year survival rates of HCC patients still remains poor. Thus, there is an urgent need to better understand the mechanisms of cancer progression in HCC and to identify useful biomarkers to predict prognosis.MethodsPublic data portals including Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) profiles were used to retrieve the HCC-related microarrays and to identify potential genes contributed to cancer progression. Bioinformatics analyses including pathway enrichment, protein/gene interaction and text mining were used to explain the potential roles of the identified genes in HCC. Quantitative real-time polymerase chain reaction analysis and Western blotting were used to measure the expression of the targets. The data were analysed by SPSS 20.0 software.ResultsWe identified 80 genes that were significantly dysregulated in HCC according to four independent microarrays covering 386 cases of HCC and 327 normal liver tissues. Twenty genes were consistently and stably dysregulated in the four microarrays by at least 2-fold and detection of gene expression by RT-qPCR and western blotting showed consistent expression profiles in 11 HCC tissues compared with corresponding paracancerous tissues. Eleven of these 20 genes were associated with disease-free survival (DFS) or overall survival (OS) in a cohort of 157 HCC patients, and eight genes were associated with tumour pathologic PT, tumour stage or vital status. Potential roles of those 20 genes in regulation of HCC progression were predicted, primarily in association with metastasis. INTS8 was specifically correlated with most clinical characteristics including DFS, OS, stage, metastasis, invasiveness, diagnosis, and age.ConclusionThe significantly dysregulated genes identified in this study were associated with cancer progression and prognosis in HCC, and might be potential therapeutic targets for HCC treatment or potential biomarkers for diagnosis and prognosis.

Project description:BackgroundHepatocellular carcinoma (HCC) is a common abdominal cancer with poor survival outcomes. Although there is growing evidence that N7-methylguanosine (m7G) is closely associated with tumor prognosis, development, and immune response, few studies focus on this topic.MethodsThe novel m7G risk signature was constructed through the Lasso regression analysis. Its prognostic value was evaluated through a series of survival analyses and was tested in ICGC-LIRI, GSE14520, and GSE116174 cohorts. CIBERSORT, ssGSEA, and ESTIMATE methods were applied to explore the effects of the m7G risk score on tumor immune microenvironment (TIM). The GSEA method was used to evaluate the impacts of the m7G risk score on glycolysis, ferroptosis, and pyroptosis. The human protein atlas (HPA) database was used to clarify the histological expression levels of five m7G signature genes. The biofunctions of NCBP2 in hepatocellular cancer (HC) cells were confirmed through qPCR, CCK8, and transwell assays.ResultsFive m7G regulatory genes comprised the novel risk signature. The m7G risk score was identified as an independent prognostic factor of HCC and could increase the decision-making benefit of traditional prognostic models. Besides, we established a nomogram containing the clinical stage and m7G risk score to predict the survival rates of HCC patients. The prognostic value of the m7G model was successfully validated in ICGC and GSE116174 cohorts. Moreover, high m7G risk led to a decreased infiltration level of CD8+ T cells, whereas it increased the infiltration levels of Tregs and macrophages. The glycolysis and pyroptosis processes were found to be enriched in the HCC patients with high m7G risk. Finally, overexpression of NCBP2 could promote the proliferation, migration, and invasion of HC cells.ConclusionsThe m7G risk score was closely related to the prognosis, antitumor immune process, glycolysis, and malignant progression of HCC. NCBP2 has pro-oncogenic abilities, showing promise as a novel treatment target.

Project description:Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Currently, overcoming the drug resistance in HCC is a critical challenge and ferroptosis has emerged as a promising therapeutic option for cancer. We aim to construct a new gene signature related to ferroptosis and drug resistance to predict the prognosis in HCC. The RNA-seq data of HCC patients was obtained from the Cancer Genome Atlas database. Using least absolute shrinkage and selection operator cox regression, Kaplan-Meier analysis, and differential analysis, we constructed a prognostic model consisting of six hub genes (TOP2A, BIRC5, VEGFA, HIF1A, FTH1, ACSL3) related to ferroptosis and drug resistance in HCC. Functional enrichment, pathway enrichment and GSEA analysis were performed to investigate the potential molecular mechanism, and construction of PPI, mRNA-miRNA, mRNA-RBP, mRNA-TF and mRNA-drugs interaction networks to predict its interaction with different molecules. Clinical prognostic characteristics were revealed by univariate, multivariate cox regression analysis and nomogram. We also analyzed the relationship between the signature, immune checkpoints, and drug sensitivity. The expression of the gene signature was detected in HCC cell lines and HPA database. Our prognostic model classified patients into high and low-risk groups based on the risk scores and found the expression level of the genes was higher in the high-risk group than the low-risk group, demonstrating that high expression of the hub genes was associated with poor prognosis in HCC. ROC analysis revealed its high diagnostic efficacy in both HCC and normal tissues. The proportional hazards model and calibration analysis confirmed that the model's prediction was most accurate for 1- and 3-years survival. QRT-PCR showed the high expression level of the gene signature in HCC. Our study built a novel gene signature with good potential to predict the prognosis of HCC, which may provide new therapeutic targets and molecular mechanism for HCC diagnosis and treatment.

Dataset Information

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication.

Background

Methods and results

Conclusion

Publications

Identification of Core Genes Related to Progression and Prognosis of Hepatocellular Carcinoma and Small-Molecule Drug Predication.

Similar Datasets

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