Department of Oncology-Pathology, Karolinska Institute and University Hospital Solna, 141 86 Stockholm, Sweden.
Cancer Centrum Karolinska, CCK, Plan 00, Visionsgatan 56, Karolinska Universitetssjukhuset, Solna, 171 64 Stockholm, Sweden.
Int J Mol Sci. 2023 Mar 8;24(6):5160. doi: 10.3390/ijms24065160.
Thymidine kinase 1 (TK1) is an intracellular enzyme involved in DNA-precursor synthesis. Increased serum TK1 levels are used as a biomarker in various malignancies. We combined serum TK1 with PSA and evaluated its capacity to predict overall survival (OS) in 175 men with prostate cancer (PCa), detected by screening in 1988-1989 ( = 52) and during follow-up (median 22.6 years) ( = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnosis and dates of death were obtained from Swedish population-based registries. The median concentration of TK1 and PSA was 0.25 and 3.8 ng/ml. TK1 was an independent variable of OS. In the multivariate analysis, PSA was not statistically significant in combination with age whereas the significance remained for TK1 + PSA. Measured once, TK1 + PSA predicted a difference of up to 10 years (depending on patient subgroup) in OS at a median of 9 years before PCa diagnosis. The TK1 concentration in 193 controls without malignancies did not differ from that of the PCa patients, hence TK1 was likely not released from incidental PCa. Thus, TK1 in the blood circulation may indicate the release of TK1 from sources other than cancers, nonetheless associated with OS.
胸苷激酶 1（TK1）是一种参与 DNA 前体合成的细胞内酶。血清 TK1 水平升高被用作各种恶性肿瘤的生物标志物。我们将血清 TK1 与 PSA 相结合，评估其在 1988-1989 年筛查时（=52）和随访期间（中位随访时间为 22.6 年）（=123）检测到的 175 例前列腺癌（PCa）男性患者中的总生存（OS）预测能力。在冷冻血清中测量 TK1，将年龄分为四组，并从瑞典基于人群的登记处获得 PCa 诊断日期和死亡日期。TK1 和 PSA 的中位数浓度分别为 0.25 和 3.8ng/ml。TK1 是 OS 的独立变量。在多变量分析中，PSA 与年龄结合时在统计学上没有意义，而 TK1 + PSA 的意义仍然存在。在 PCa 诊断前 9 年的中位数时，单次测量的 TK1 + PSA 预测 OS 差异可达 10 年（取决于患者亚组）。193 例无恶性肿瘤的对照者的 TK1 浓度与 PCa 患者的浓度没有差异，因此 TK1 不太可能是偶然的 PCa 释放的。因此，血液循环中的 TK1 可能表明除癌症以外的来源释放了 TK1，但与 OS 相关。
