Dataset Information

Bioinformatics analysis of the proteins interacting with LASP-1 and their association with HBV-related hepatocellular carcinoma.

ABSTRACT: LIM and SH3 domain protein (LASP-1) is responsible for the development of several types of human cancers via the interaction with other proteins; however, the precise biological functions of proteins interacting with LASP-1 are not fully clarified. Although the role of LASP-1 in hepatocarcinogenesis has been reported, the implication of LASP-1 interactors in HBV-related hepatocellular carcinoma (HCC) is not clearly evaluated. We obtained information regarding LASP-1 interactors from public databases and published studies. Via bioinformatics analysis, we found that LASP-1 interactors were related to distinct molecular functions and associated with various biological processes. Through an integrated network analysis of the interaction and pathways of LASP-1 interactors, cross-talk between different proteins and associated pathways was found. In addition, LASP-1 and several its interactors are significantly altered in HBV-related HCC through microarray analysis and could form a complex co-expression network. In the disease, LASP-1 and its interactors were further predicted to be regulated by a complex interaction network composed of different transcription factors. Besides, numerous LASP-1 interactors were associated with various clinical factors and related to the survival and recurrence of HBV-related HCC. Taken together, these results could help enrich our understanding of LASP-1 interactors and their relationships with HBV-related HCC.

SUBMITTER: Kong FY

PROVIDER: S-EPMC5339786 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Bioinformatics analysis of the proteins interacting with LASP-1 and their association with HBV-related hepatocellular carcinoma.

Kong Fan-Yun FY Zhu Ting T Li Nan N Cai Yun-Fei YF Zhou Kai K Wei Xiao X Kou Yan-Bo YB You Hong-Juan HJ Zheng Kui-Yang KY Tang Ren-Xian RX

Scientific reports 20170307

LIM and SH3 domain protein (LASP-1) is responsible for the development of several types of human cancers via the interaction with other proteins; however, the precise biological functions of proteins interacting with LASP-1 are not fully clarified. Although the role of LASP-1 in hepatocarcinogenesis has been reported, the implication of LASP-1 interactors in HBV-related hepatocellular carcinoma (HCC) is not clearly evaluated. We obtained information regarding LASP-1 interactors from public datab ...[more]

PMID: 28266596

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Project description:BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor affecting the digestive system and causes serious financial burden worldwide. Hepatitis B virus (HBV) is the main causative agent of HCC in China. The present study aimed to investigate the potential mechanisms underlying HBV-related HCC and to identify core biomarkers by integrated bioinformatics analyses.MethodsIn the present study, HBV-related HCC GSE19665, GSE55092, GSE94660 and GSE121248 expression profiles were downloaded from the Gene Expression Omnibus database. These databases contain data for 299 samples, including 145 HBV-related HCC tissues and 154 non-cancerous tissues (from patients with chronic hepatitis B). The differentially expressed genes (DEGs) from each dataset were integrated and analyzed using the RobustRankAggreg (RRA) method and R software, and the integrated DEGs were identified. Subsequently, the gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the DAVID online tool, and the protein-protein interaction (PPI) network was constructed using STRING and visualized using Cytoscape software. Finally, hub genes were identified, and the cBioPortal online platform was used to analyze the association between the expression of hub genes and prognosis in HCC.ResultsFirst, 341 DEGs (117 upregulated and 224 downregulated) were identified from the four datasets. Next, GO analysis showed that the upregulated genes were mainly involved in cell cycle, mitotic spindle, and adenosine triphosphate binding. The majority of the downregulated genes were involved in oxidation reduction, extracellular region, and electron carrier activity. Signaling pathway analysis showed that the integrated DEGs shared common pathways in retinol metabolism, drug metabolism, tryptophan metabolism, caffeine metabolism, and metabolism of xenobiotics by cytochrome P450. The integrated DEG PPI network complex comprised 288 nodes, and two important modules with high degree were detected using the MCODE plug-in. The top ten hub genes identified from the PPI network were SHCBP1, FOXM1, KIF4A, ANLN, KIF15, KIF18A, FANCI, NEK2, ECT2, and RAD51AP1. Finally, survival analysis revealed that patients with HCC showing altered ANLN and KIF18A expression profiles showed worse disease-free survival. Nonetheless, patients with FOXM1, NEK2, RAD51AP1, ANLN, and KIF18A alterations showed worse overall survival.ConclusionsThe present study identified key genes and pathways involved in HBV-related HCC, which improved our understanding of the mechanisms underlying the development and recurrence of HCC and identified candidate targets for the diagnosis and treatment of HBV-related HCC.

Project description:Hepatocellular carcinoma (HCC) is the most common type of malignant neoplasm of the liver with high morbidity and mortality. Extensive research into the pathology of HCC has been performed; however, the molecular mechanisms underlying the development of hepatitis B virus-associated HCC have remained elusive. Thus, the present study aimed to identify critical genes and pathways associated with the development and progression of HCC. The expression profiles of the GSE121248 dataset were downloaded from the Gene Expression Omnibus database and the differentially expressed genes (DEGs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) analyses were performed by using the Database for Annotation, Visualization and Integrated Discovery. Subsequently, protein-protein interaction (PPI) networks were constructed for detecting hub genes. In the present study, 1,153 DEGs (777 upregulated and 376 downregulated genes) were identified and the PPI network yielded 15 hub genes. GO analysis revealed that the DEGs were primarily enriched in 'protein binding', 'cytoplasm' and 'extracellular exosome'. KEGG analysis indicated that DEGs were accumulated in 'metabolic pathways', 'chemical carcinogenesis' and 'fatty acid degradation'. After constructing the PPI network, cyclin-dependent kinase 1, cyclin B1, cyclin A2, mitotic arrest deficient 2 like 1, cyclin B2, DNA topoisomerase IIα, budding uninhibited by benzimidazoles (BUB)1, TTK protein kinase, non-SMC condensin I complex subunit G, NDC80 kinetochore complex component, aurora kinase A, kinesin family member 11, cell division cycle 20, BUB1B and abnormal spindle microtubule assembly were identified as hub genes based on the high degree of connectivity by using Cytoscape software. In addition, overall survival (OS) and disease-free survival (DFS) analyses were performed using the Gene Expression Profiling Interactive Analysis online database, which revealed that the increased expression of all hub genes were associated with poorer OS and DFS outcomes. Receiver operating characteristic curves were constructed using GraphPad prism 7.0 software. The results confirmed that 15 hub genes were able to distinguish HCC form normal tissues. Furthermore, the expression levels of three key genes were analyzed in tumor and normal samples of the Human Protein Atlas database. The present results may provide further insight into the underlying mechanisms of HCC and potential therapeutic targets for the treatment of this disease.

Dataset Information

Bioinformatics analysis of the proteins interacting with LASP-1 and their association with HBV-related hepatocellular carcinoma.

Publications

Bioinformatics analysis of the proteins interacting with LASP-1 and their association with HBV-related hepatocellular carcinoma.

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