Dataset Information

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

ABSTRACT: 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 (n = 52) and during follow-up (median 22.6 years) (n = 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.

SUBMITTER: Tribukait B

PROVIDER: S-EPMC10049218 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Tribukait Bernhard B Lundgren Per-Olof PO Kjellman Anders A Norming Ulf U Nyman Claes R CR Jagarlmundi Kiran K Gustafsson Ove O

International journal of molecular sciences 20230308 6

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 (<i>n</i> = 52) and during follow-up (median 22.6 years) (<i>n</i> = 123). TK1 was measured in frozen serum, age was stratified into four groups, and dates of PCa diagnos ...[more]

PMID: 36982234

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Project description:Background and objectiveProstate-specific antigen (PSA) is of limited value as a surrogate marker for overall survival (OS) in prostate cancer (PC). Serum thymidine kinase 1 (sTK1) is an enzyme expressed by actively dividing cells. Our aim was to evaluate the value of sTK1 as prognostic biomarker in metastatic hormone-sensitive PC (mHSPC) and metastatic castration-resistant PC (mCRPC).MethodssTK1 was examined in three cohorts: (1) 43 men with de novo mHSPC managed with androgen deprivation monotherapy; (2) 99 patients with mCRPC managed with androgen receptor signaling inhibitors (ARSIs); and (3) 98 patients with mCRPC treated with docetaxel. sTK1 levels were determined at treatment initiation. OS was evaluated using Cox regression analysis.Key findings and limitationsIn the mHSPC cohort, sTK1 levels in the highest quartile were associated with OS (hazard ratio [HR] 7.77, 95% confidence interval [CI] 2.25-26.9) in comparison to the lowest quartile after multivariable adjustment for age, Gleason score, and PSA. Similarly, sTKI was associated with poor OS in the mCRPC group treated with ARSIs (upper quartile: HR 5.22, 95% CI 2.23-12.2) after multivariable adjustment for age, PSA, and Eastern Cooperative Oncology Group performance status. In the docetaxel-treated mCRPC group the association between OS and sTK1 was lower but still significant (multivariable-adjusted HR 2.28, 95% CI 1.13-4.60). Limitations include the nonrandomized inclusion of patients for different treatments, which could lead to selection bias.Conclusions and clinical implicationssTK1 predicted OS in mHSPC and mCRPC, demonstrating additional value over established clinical risk factors. sTK1 should be measured in randomized clinical trials of treatments for advanced PC to validate its predictive value.Patient summaryWe found that for patients with metastatic prostate cancer, high levels of a protein called TK1 that is involved in cell division was linked to higher risk of death. Our findings need to be confirmed in other studies.

Project description:BackgroundProstate-specific antigen (PSA) measurement in midlife predicts long-term prostate cancer (PCa) mortality among white men.ObjectiveTo determine whether baseline PSA level during midlife predicts risk of aggressive PCa in black men.Design, setting, and participantsNested case-control study among black men in the Southern Community Cohort Study recruited between 2002 and 2009. A prospective cohort in the southeastern USA with recruitment from community health centers. A total of 197 incident PCa patients aged 40-64 yr at study entry and 569 controls matched on age, date of blood draw, and site of enrollment. Total PSA was measured in blood collected and stored at enrollment.Outcome measurements and statistical analysisTotal and aggressive PCa (91 aggressive: Gleason ≥7, American Joint Committee on Cancer stage III/IV, or PCa-specific death). Exact conditional logistic regression estimated odds ratios (ORs) with 95% confidence intervals (CIs) for PCa by category of baseline PSA.Results and limitationsMedian PSA among controls was 0.72, 0.80, 0.94, and 1.03ng/ml for age groups 40-49, 50-54, 55-59, and 60-64 yr, respectively; 90th percentile levels were 1.68, 1.85, 2.73, and 3.33ng/ml. Furthermore, 95% of total and 97% of aggressive cases had baseline PSA above the age-specific median. Median follow-up was 9 yr. The OR for total PCa comparing PSA >90th percentile versus ≤median was 83.6 (95% CI, 21.2-539) for 40-54 yr and 71.7 (95% CI, 23.3-288) for 55-64 yr. For aggressive cancer, ORs were 174 (95% CI, 32.3-infinity) for 40-54 yr and 51.8 (95% CI, 11.0-519) for 55-64 yr. A composite endpoint of aggressive PCa based on stage, grade, and mortality was used and is a limitation.ConclusionsPSA levels in midlife strongly predicted total and aggressive PCa among black men. PSA levels among controls were similar to those among white controls in prior studies.Patient summaryProstate-specific antigen (PSA) level during midlife strongly predicted future development of aggressive prostate cancer among black men. Targeted screening based on a midlife PSA might identify men at high risk while minimizing screening in those men at low risk.

Dataset Information

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

Publications

Prediction of Overall Survival by Thymidine Kinase 1 Combined with Prostate-Specific Antigen in Men with Prostate Cancer.

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