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15 November 2019 : Clinical Research  

Bioinformatics Analysis Identifies Protein Tyrosine Kinase 7 (PTK7) as a Potential Prognostic and Therapeutic Biomarker in Stages I to IV Hepatocellular Carcinoma

Ren-Chao Zou12ABCDEF, Yun Liang23BD, Ling-Lin Li1BD, Jian-Zhong Tang4C, Yan-Ping Yang1C, Yan-Chun Geng1C, Jie He1DF, Li-Yun Luo3D, Wen-Xing Li56ABCDEF, Zhi-Wei Sun4AG, Hong-Ling Yuan1AG*

DOI: 10.12659/MSM.917142

Med Sci Monit 2019; 25:8618-8627

Abstract

BACKGROUND: Worldwide, hepatocellular carcinoma (HCC) accounts for 80–90% of all cases of primary liver cancer, and is one of the ten most common malignancies. This study used bioinformatics analysis to identify genes associated with patient outcome in stages I–IV HCC and the gene pathways that distinguished between normal liver and liver cells and HCC and human HCC cell lines.

MATERIAL AND METHODS: Target genes were defined as those that had marketed drugs or drugs under development targeting a specific gene and acquired from the Clarivate Analytics Integrity Database. Differential expression gene analysis, co-expression network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, survival analysis and receiver operating characteristic (ROC) curve analysis were used to explore the similarities and differences in gene expression profiles, functional associations, and survival in stage I–IV HCC. Normal liver cells (HL-7702) and HCC cell lines (HepaRG, HepG2, SK-Hep1, and Huh7) were studied using Western blot and quantitative reverse transcription PCR (RT-qPCR).

RESULTS: Hierarchical gene clustering identified target genes that distinguished between HCC and normal liver tissue. For stages I–IV HCC, there were seven commonly upregulated target genes EPHB1, LTK, NTRK2, PTK7, TBK1, TIE1, and TLR3, which were mainly involved in immune and signaling transduction pathways. PTK7 was highly expressed in stage I–IV HCC and was an independent prognostic marker for reduced overall survival (OS).

CONCLUSIONS: Bioinformatics analysis, combined with patient survival analysis, identified PTK7 gene expression as a potential therapeutic target and prognostic biomarker for all stages of HCC.

Keywords: hepatocellular carcinoma, Gene Targeting, Biomarkers, Tumor, Carcinoma, Hepatocellular, Cell Adhesion Molecules, Cluster Analysis, Computational Biology, Databases, Genetic, Gene Expression Profiling, Liver Neoplasms, Protein Interaction Maps, ROC Curve, Receptor Protein-Tyrosine Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750