Microarray analysis for the identification of specific proteins and functional modules involved in the process of hepatocellular carcinoma originating from cirrhotic liver

Abstract

In order to identify the potential pathogenesis of hepatocellular carcinoma (HCC) developing from cirrhosis, a microarray-based transcriptome profile was analyzed. The GSE63898 expression profile was downloaded from the Gene Expression Omnibus database, which included data from 228 HCC tissue samples and 168 cirrhotic tissue samples. The Robust Multi-array Average in the Affy package of R was used for raw data processing and Student's t-test was used to screen differentially expressed genes (DEGs). An enrichment analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery online tool, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape. Furthermore, the MCODE plug-in of Cytoscape was used to conduct a sub-module analysis. A total of 634 DEGs were identified between HCC and cirrhosis, of which 165 were upregulated and 469 were downregulated. According to the cut-off criteria, the PPI network was constructed and Jun proto-oncogene, AP-1 transcription factor subunit (degree, 39), Fos proto-oncogene, AP-1 transcription factor subunit (degree, 34) and v-myc avian myelocytomatosis viral oncogene homolog (degree, 32) were identified as the hub nodes of the PPI network. Based on the sub-module analysis, four specific modules were identified. In particular, module 1 was significantly enriched in the chemokine signaling pathway, and C-X-C motif chemokine ligand 12, C-C motif chemokine receptor 7 (CCR7) and C-C motif chemokine ligand 5 (CCL5) were three important proteins in this module. Module 4 was significantly enriched in chemical carcinogenesis, and cytochrome P450 family 2 subfamily E member 1, cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily A member 6 (CYP2A6) were three important proteins in this module. In conclusion, the present study revealed that CCR7, CCL5, CYP2C9 and CYP2A6 are novel genes identified in the development of HCC; however, the actual functions of these genes require verification.

Dissecting the expression landscape of cytochromes P450 in hepatocellular carcinoma: towards novel molecular biomarkers

“…Differential gene expression levels of various CYP450s have previously been reported [23–26]. However, these previous studies were generally performed on a limited number of HCC tissue samples or focused on a small subset on CYP450s [23–26].…”

“…Differential gene expression levels of various CYP450s have previously been reported [23–26]. However, these previous studies were generally performed on a limited number of HCC tissue samples or focused on a small subset on CYP450s [23–26]. In humans, 57 CYP450 genes are expressed in multiple tissues such as liver, placenta, brain, kidney, and intestines where they catalyze monooxygenase activity on specific substrates [17, 18].…”

“…Advances in genomic technologies have allowed the characterization of molecular events occurring during carcinogenesis, such as mRNA expression dysregulation, which could potentially lead to the identification of new biomarkers. In the case of HCC, differential gene expression levels of various CYP450s have previously been reported [23–26]. However, these previous studies were generally performed on a limited number of HCC tissue samples or focused on a small subset on CYP450s.…”

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

“…The proliferation of esophageal cancer is e ciently inhibited in patients with highly expressed CYP2C9 [47]. Moreover, CYP2C9 is a hub gene that affects the transformation from hepatic cirrhosis into HCC [48,49]. In the present work, the mRNA expression levels of CYP2B6, CYP2C8, and CYP2C9 remarkably decreased and were negatively correlated with individual cancer stages and tumor grades.…”

Investigation of key miRNAs and potential mechanisms in non-small cell lung cancer development from chronic obstructive pulmonary disease

“…JUN (degree = 41), IL-6 (degree = 41) and CD4 (degree = 29) were validated in LUAD and LUSC by using UALCAN. Jun proto-oncogene, activator protein-1 transcription factor subunit (JUN), is important for cell proliferation, survival, and apoptosis, and was reported to be a crucial contributing factor for tumorigenesis due to its downregulation in numerous types of human cancer (Fan and Ye 2018). IL-6 is one of the most important regulators of the cytokinerelated tumor biology (Łukaszewicz et al 2007).…”