Abstract
Increased expression of TK1 is associated with the progression of a variety of tumors. However, the relationship of TK1 expression with immune cell infiltration and its prognostic value in hepatocellular carcinoma (HCC) are still unknown. In this study the TCGA database was used to evaluate TK1 expression and its impact on survival in patients with HCC. Compared with normal tissue, TK1 in the liver tissue of patients with HCC was significantly up-regulated at both the mRNA and protein levels. Furthermore, TK1 expression was significantly related to pathological stage, tumor stage and lymph node metastasis, with high TK1 expression being an unfavorable prognostic factor for HCC. TK1 expression was also significantly associated with the infiltration of B cells, T cells, and dendritic cells in HCC. Single-cell sequencing analysis revealed that TK1 was associated with relatively large changes in T cells, especially gamma-delta T cells. A prognostic risk score based on TK1-related immune genes (CD40LG and TNFRSF4) was established using COX regression analysis. By integrating the immune-related risk score model with clinical features, a nomogram was constructed to predict the survival rate of HCC patients (1 year, 3-year and 5-year AUC of 0.782, 0.783 and 0.771, respectively). Knockdown of the target gene for TK1 was found to have significant anti-apoptosis and pro-proliferation effects on HepG2 cells. The level of TK1 in the serum and liver tissue of patients with HCC was significantly increased relative to healthy controls. These findings highlight the role of TK1 in the tumor immune response of HCC patients and in the proliferation and apoptosis of HepG2 cells. TK1 could therefore be a potential immunotherapy target for HCC patients, while the two immune genes related to TK1 (CD40LG And TNFRSF4) may be promising prognostic biomarkers in HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is characterized by an extremely high recurrence rate and heterogeneity [1]
We examined genes that are significantly related to Thymidine kinase 1 (TK1)
Gene Ontology (GO) analysis showed these genes are mainly involved in: “nuclear division”, “organelle fission”, “DNA replication”, and “mitotic nuclear division” in Biological Process (BP); “chromosomal region” and “condensed chromosome” in Cellular Component (CC); “tubulin binding”, “microtubule binding”, “catalytic activity acting on DNA”, and “single−stranded DNA binding” in Molecular Function (MF) (Figure 2A)
Summary
Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is characterized by an extremely high recurrence rate and heterogeneity [1]. Chronic viral infection with hepatitis B (HBV) or C (HCV) is the main cause of HCC [2], and in recent years the incidence and mortality of this disease have gradually increased [3]. Treatment for HCC varies according to the stage of disease. Surgical resection or local ablation is generally used for early stage HCC, trans arterial chemoembolization (TACE) is used for intermediate or systemic HCC, while advanced HCC is mostly treated with drugs. HCC often develops to an advanced stage before being diagnosed, and the tumor recurrence rate is as high as 50% within 3 years after treatment [4]. Many studies have suggested there are significant changes in the expression of immune cells in HCC, the key genes that connect immunity and HCC are poorly understood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
