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

被引:15
作者
Cai, Qun [1 ]
Zhu, Mingyan [1 ]
Duan, Jinnan [2 ]
Wang, Hao [3 ]
Chen, Jingdan [1 ]
Xiao, Yixin [1 ]
Wang, Yangqin [1 ]
Wang, Jianfang [1 ]
Yu, Xuewen [1 ]
Yang, Hui [1 ]
机构
[1] Ningbo Univ, Ningbo Med Ctr Lihuili Hosp, Dept Infect Dis & Liver Dis, Affiliated Lihuili Hosp, Ningbo, Peoples R China
[2] Shaoxing Peoples Hosp, Dept Infect Dis, Shaoxing, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 1, Coll Med,Natl Clin Res Ctr Infect Dis,Collaborat, Dept Infect Dis,State Key Lab Diag & Treatment In, Hangzhou, Peoples R China
关键词
liver hepatocellular carcinoma; thymidine kinase 1; biomarker; overall survival; signature; nomogram; DELTA T-CELLS; TUMOR;
D O I
10.3389/fonc.2021.786873
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页数:9
相关论文
共 39 条
[1]   Identification of important invasion and proliferation related genes in adrenocortical carcinoma [J].
Alshabi, Ali Mohamed ;
Vastrad, Basavaraj ;
Shaikh, Ibrahim Ahmed ;
Vastrad, Chanabasayya .
MEDICAL ONCOLOGY, 2019, 36 (09)
[2]   Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage [J].
Aran, Dvir ;
Looney, Agnieszka P. ;
Liu, Leqian ;
Wu, Esther ;
Fong, Valerie ;
Hsu, Austin ;
Chak, Suzanna ;
Naikawadi, Ram P. ;
Wolters, Paul J. ;
Abate, Adam R. ;
Butte, Atul J. ;
Bhattacharya, Mallar .
NATURE IMMUNOLOGY, 2019, 20 (02) :163-+
[3]   REGULATION OF THYMIDINE KINASE SYNTHESIS IN HUMAN CELLS [J].
BELLO, LJ .
EXPERIMENTAL CELL RESEARCH, 1974, 89 (02) :263-274
[4]   Metabolic Regulation by p53 Family Members [J].
Berkers, Celia R. ;
Maddocks, Oliver D. K. ;
Cheung, Eric C. ;
Mor, Inbal ;
Vousden, Karen H. .
CELL METABOLISM, 2013, 18 (05) :617-633
[5]   Thymidine kinase 1 through the ages: a comprehensive review [J].
Bitter, Eliza E. ;
Townsend, Michelle H. ;
Erickson, Rachel ;
Allen, Carolyn ;
O'Neill, Kim L. .
CELL AND BIOSCIENCE, 2020, 10 (01)
[6]   Integrating single-cell transcriptomic data across different conditions, technologies, and species [J].
Butler, Andrew ;
Hoffman, Paul ;
Smibert, Peter ;
Papalexi, Efthymia ;
Satija, Rahul .
NATURE BIOTECHNOLOGY, 2018, 36 (05) :411-+
[7]   Low Counts of γδ T Cells in Peritumoral Liver Tissue are Related to More Frequent Recurrence in Patients with Hepatocellular Carcinoma after Curative Resection [J].
Cai, Xiao-Yan ;
Wang, Jia-Xing ;
Yi, Yong ;
He, Hong-Wei ;
Ni, Xiao-Chun ;
Zhou, Jian ;
Cheng, Yun-Feng ;
Jin, Jian-Jun ;
Fan, Jia ;
Qiu, Shuang-Jian .
ASIAN PACIFIC JOURNAL OF CANCER PREVENTION, 2014, 15 (02) :775-780
[8]   Promotion of Hepatocellular Carcinoma by the Intestinal Microbiota and TLR4 [J].
Dapito, Dianne H. ;
Mencin, Ali ;
Gwak, Geum-Youn ;
Pradere, Jean-Philippe ;
Jang, Myoung-Kuk ;
Mederacke, Ingmar ;
Caviglia, Jorge M. ;
Khiabanian, Hossein ;
Adeyemi, Adebowale ;
Bataller, Ramon ;
Lefkowitch, Jay H. ;
Bower, Maureen ;
Friedman, Richard ;
Sartor, R. Balfour ;
Rabadan, Raul ;
Schwabe, Robert F. .
CANCER CELL, 2012, 21 (04) :504-516
[9]   Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma [J].
Feng, Jiao ;
Li, Jingjing ;
Wu, Liwei ;
Yu, Qiang ;
Ji, Jie ;
Wu, Jianye ;
Dai, Weiqi ;
Guo, Chuanyong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2020, 39 (01)
[10]   PER1 suppresses glycolysis and cell proliferation in oral squamous cell carcinoma via the PER1/RACK1/PI3K signaling complex [J].
Gong, Xiaobao ;
Tang, Hong ;
Yang, Kai .
CELL DEATH & DISEASE, 2021, 12 (03)