基于生物信息学探讨胸苷激酶1在前列腺癌中的表达及临床意义

Expression and clinical significance of thymidine kinase 1 in prostate cancer based on bioinformatics

  • 摘要:
    目的 基于生物信息学探究胸苷激酶1(TK1)在前列腺癌中的表达及临床意义。
    方法 利用TCGA数据库中的前列腺癌转录组数据, 评估TK1作为前列腺癌预后标志物的价值及其生物学意义。根据TK1表达水平的中位数将前列腺癌患者分为TK1高表达组与TK1低表达组。筛选2组差异表达基因,并进行功能富集分析。分析TK1与肿瘤浸润免疫细胞和免疫治疗反应的相关性。
    结果 TK1高表达组的总生存期(OS)为(2.77±0.19)年,短于TK1低表达组的(3.20±0.24)年,差异有统计学意义(P=0.017); TK1高表达组的无进展生存期(PFS)为(2.65±0.17)年,短于TK1低表达组的(3.13±0.27)年,差异有统计学意义(P < 0.001)。TK1相关基因主要涉及染色体分离、有丝分裂以及细胞周期。TK1高表达组的活化记忆CD4+ T细胞与M1型巨噬细胞的浸润水平高于TK1低表达组,差异有统计学意义(P < 0.05)。TK1高表达患者的免疫表型评分(IPS)更低。
    结论 TK1可能通过调节肿瘤微环境影响前列腺癌的进展。TK1或可作为前列腺癌预后的潜在生物标志物和治疗靶点。

     

    Abstract:
    Objective To explore the expression and clinical significance of thymidine kinase 1 (TK1) in prostate cancer using bioinformatic approaches.
    Methods Prostate cancer transcriptomic data from TCGA database were used to evaluate the prognostic value and biological relevance of TK1 in prostate cancer. Patients were stratified into high- and low-TK1 expression groups based on the median expression level of TK1. Differentially expressed genes between the two groups were identified, followed by functional enrichment analysis. The association between TK1 expression and tumor-infiltrating immune cells as well as response to immunotherapy was also assessed.
    Results The overall survival (OS) in the high-TK1 expression group was (2.77±0.19) years, which was significantly lower than that in the low-TK1 expression group(3.20±0.24) years; P=0.017. Similarly, progression-free survival (PFS) was shorter in the high-TK1 group(2.65±0.17) yearscompared with the low-TK1 group(3.13±0.27) years; P < 0.001. Genes associated with TK1 were primarily enriched in pathways related to chromosome segregation, mitosis, and the cell cycle. Infiltration levels of activated memory CD4+ T cells and M1 macrophages were significantly higher in the high-TK1 group than in the low-TK1 group (P < 0.05). Patients with high TK1 expression exhibited lower immunophenotype scores (IPS).
    Conclusion TK1 may influence the progression of prostate cancer by modulating the tumor microenvironment. TK1 may serve as a potential biomarker and therapeutic target for the prognosis of prostate cancer.

     

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