Interaction of key pathways in sorafenib-treated hepatocellular carcinoma based on a PCR-array.

Abstract

This study aimed to identify the key pathways and to explore the mechanism of sorafenib in inhibiting hepatocellular carcinoma (HCC). The gene expression profile of GSE33621, including 6 sorafenib treated group and 6 control samples, was downloaded from the GEO (Gene Expression Omnibus) database. The differentially expressed genes (DEGs) in HCC samples were screened using the ΔΔCt method with the homogenized internal GAPDH. Also, the functions and pathways of DEGs were analyzed using the DAVID. Moreover, the significant pathways of DEGs that involved in HCC were analyzed based on the Latent pathway identification analysis (LPIA). A total of 44 down-regulated DEGs were selected in HCC samples. Also, there were 84 biological pathways that these 44 DEGs involved in. Also, LPIA showed that Osteoclast differentiation and hsa04664-Fc epsilon RI signaling pathway was the most significant interaction pathways. Moreover, Apoptosis, Toll-like receptor signaling pathway, Chagas disease, and T cell receptor signaling pathway were the significant pathways that interacted with hsa04664. In addition, DEGs such as AKT1 (v-akt murine thymoma viral oncogene homolog 1), TNF (tumor necrosis factor), SYK (spleen tyrosine kinase), and PIK3R1 (phosphoinositide-3-kinase, regulatory subunit 1 (alpha)) were the common genes that involved in the significant pathways. Several pathway interaction pairs that caused by several downregulated genes such as SYK, PI3K, AKT1, and TNF, were identified play curial role in sorafenib treated HCC. Sorafenib played important inhibition roles in HCC by affecting a complicate pathway interaction network.

• Authors: Yan Liu, Ping Wang, Shijie Li, Linan Yin, Haiyang Shen, Ruibao Liu
• Journal: International journal of clinical and experimental pathology (Int J Clin Exp Pathol) Vol. 8 Issue 3 Pg. 3027-35 ( 2015) ISSN: 1936-2625 [Electronic] United States
• PMID: 26045814 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Phenylurea Compounds
• Niacinamide
• Sorafenib

Topics

• Antineoplastic Agents (therapeutic use)
• Carcinoma, Hepatocellular (drug therapy, genetics)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects, genetics)
• Humans
• Liver Neoplasms (drug therapy, genetics)
• Niacinamide (analogs & derivatives, therapeutic use)
• Oligonucleotide Array Sequence Analysis
• Phenylurea Compounds (therapeutic use)
• Polymerase Chain Reaction
• Signal Transduction (drug effects, genetics)
• Sorafenib