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

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/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.

PTK7-Targeting CAR T-Cells for the Treatment of Lung Cancer and Other Malignancies

“…Oncogenic functions of PTK7 have been documented in several hematological and solid tumors (10,11). Recent studies showed that PTK7 is overexpressed in triplenegative breast cancer (TNBC), non-small-cell lung cancer (NSCLC), ovarian cancer (OVCA), cervical cancer, esophageal squamous cell carcinoma (ESCC), and hepatocellular carcinoma (HCC) and enriched in tumor-initiating cells (TICs) from TNBC, OVCA, and NSCLC patient-derived xenografts (PDXs), and its overexpression is associated with poor survival in NSCLC, cervical cancer, ESCC, and HCC (12,(17)(18)(19)(20)(21)(22). Bie J et al found that PTK7 was dramatically upregulated in the ESCC tissues and cancer stem cell (CSC)-like cells and its knockdown reduced sphere formation, promoted apoptosis, and suppressed invasive behavior of tumor cells (17).…”

Protein Tyrosine Kinase 7 Regulates EGFR/Akt Signaling Pathway and Correlates With Malignant Progression in Triple-Negative Breast Cancer

“…The expression and function of PTK7 have been investigated in several human cancers, although controversial results have been obtained (18)(19)(20)(21)(22)(23)(24). PTK7 is highly expressed and plays an oncogenic role in lung adenocarcinoma (18).…”

“…PTK7 is overexpressed and contributes to thyroid (19) and cervical (22) cancer progression. A bioinformatics analysis reported that PTK7 is highly expressed in stage I-IV hepatocellular carcinoma (HCC) and considered as an independent prognostic marker for reduced overall survival (21). Another investigation of PTK7 expression in 79 consecutive invasive breast cancer tissues by immunohistochemistry found that PTK7 expression level negatively associates with tumor grade and lymph node metastasis (23).…”

miR-155-5p increases the sensitivity of liver cancer cells to adriamycin by regulating ATG5-mediated autophagy

“…especially in China. Moreover, less than 20% of patients with this malignant tumor are still alive more than half a year after diagnosis [1][2][3][4]. For many years, efforts towards the treatment of liver cancer were focused on the liver cancer cells themselves.…”