Comprehensive Analysis of Immune-Related Prognosis of TK1 in Hepatocellular Carcinoma

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.

SOCS3 Acts as an Onco-immunological Biomarker With Value in Assessing the Tumor Microenvironment, Pathological Staging, Histological Subtypes, Therapeutic Effect, and Prognoses of Several Types of Cancer

“…As for these SOCS3-related genes, we found that they were associated with tumor progression and their expression was increased during tumorigenesis. For example, the mRNA and protein levels of TK1 in liver tissues and the serum of patients with liver cancer were significantly increased, while the TK1 target gene knockdown had significant anti-apoptotic and proliferative effects on HepG2 cells (36). Interestingly, these gene alterations were similar to those of SOCS3 (Figures 9D-F), suggesting that these genes are functional partners associated with carcinogenic effects of SOCS3 in tumors.…”

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC

“…We developed a novel lncRNA-derived, immune-related prognostic score based on machine learning integration. This was able to predict 5-year survival rates for HCC patients with an AUC as high as 0.912, which is significantly higher than current prognostic scoring systems (Cai et al 2021 , 2022 ; Lu et al 2022 ; Chen et al 2022 ). Cases were separated into high- or low-score groups according to the overall median score.…”

An immune-related gene prognostic risk index for pancreatic adenocarcinoma

“…VCAM1 expression is associated with the tumorigenesis and unfavorable prognosis of high-grade serous ovarian cancer ( 37 ). TNFRSF4 may be a promising immunotherapy target and prognostic biomarker for liver cancer ( 38 ). TRAF1 is important in the maintenance of immune function of CD8+T cells ( 39 ).…”