The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients.
The aim of ...this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA.
A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (
< 0.0001).
The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.
Ovarian cancer is the eighth most common cause of cancer death in women. One of the major concerns is almost two-thirds of cases are typically diagnosed in the late stage as the symptoms are ...unspecific in the early stage of ovarian cancer. It is known that the combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone. That is why, the aim of the study was to investigate whether the TK1-specific activity (TK1 SA) could function as a complement marker for early-stage diagnosis of ovarian cancer.
The study included a set of 198 sera consisting of 134 patients with ovarian tumors (72 benign and 62 malignant) and 64 healthy age-matched controls. The TK1 SA was determined using TK1 activity by TK-Liaison and TK1 protein by AroCell TK 210 ELISA. Further, CA 125, HE4, as well as risk of ovarian malignancy algorithm index were also determined in the same set of clinical samples.
The TK1 SA was significantly different between healthy compared to ovarian cancer patients (p < 0.0001). Strikingly, TK1 SA has higher sensitivity (55%) compared to other biomarkers in the detection of benign ovarian tumors. Further, the highest sensitivity was achieved by the combination of TK1 SA with CA 125 and HE4 for the detection of benign tumors as well as malignant ovarian tumors (72.2% and 88.7%). In addition, TK1 SA could significantly differentiate FIGO stage I/II from stage III/IV malignancies (p = 0.026). Follow-up of patients after surgery and chemotherapy showed a significant difference compared to TK1 SA at the time of diagnosis.
These results indicate that TK1 SA is a promising blood-based biomarker that could complement CA 125 and HE4 for the detection of early stages of ovarian cancer.
Abstract
Background: Thymidine Kinase 1 (TK1) is an ATP dependent enzyme involved in DNA precursor synthesis. It is released into the blood from cells undergoing un-controlled proliferation where it ...forms stable aggregates. Serum TK1 activity has been used as a biomarker for diagnosis and monitoring of hematological malignancies. Several commercial assays are available for measuring serum TK1 activity but they require radioactive materials or special instruments. To overcome these, AroCell has developed the TK 210 ELISA for TK1 protein measurements. In this study, we compared the performance of the TK 210 ELISA to that of the TK-Liaison assay on sera from subjects with hematological and solid tumors
Experimental Procedures Sera from patients with hematologic malignancies (N=51) were collected at the University Hospital, Uppsala. Samples from solid tumors breast cancer (n=60); subjects with benign prostate hyperplasia or prostate carcinoma (n=60) along with blood donors (N=102) were collected at the University Medical Centre, Ljubljana. TK1 protein levels were determined with AroCell TK 210 ELISA and TK1 activity levels by the TK-Liaison assay.
Results In blood donors, the TK1 protein levels were in the range of 0.1 to 0.35 µg/L with a median value of 0.2. Men had a higher median value TK1 protein levels compared to women (0.21 vs 0.19) with no significant difference. Both the TK 210 ELISA and the TK-Liaison assays showed significantly higher TK1 levels in hematological and solid tumors compared to blood donors (P<0.0001). ROC curve analysis demonstrated that across all malignancies, at 96% specificity, TK 210 ELISA (cut-off value of 0.34 µg/L) gave a higher sensitivity of 0.43 compared to TK-Liaison assay (cut-off value of 10 U/L) of 0.36. The performance of the assays differed depending on the type of malignancy, TK 210 ELISA and TK-Liaison had a similar sensitivity (0.65) for hematological malignancies. However, in the case of solid tumors, TK 210 ELISA showed a higher sensitivity (0.35) compared to TK-Liaison (0.26) at a specificity of 0.96. A regression analysis of the TK 210 ELISA (y) and TK-Liaison (x) assays across all three groups gave an equation of y = 0.15 + 0.017x (rs = 0.80, n = 273). The correlation value in hematological malignancies was higher than in blood donors and solid tumors (0.95 vs. 0.67 and 0.50 respectively).
Conclusions This study showed that the AroCell TK 210 ELISA has a similar sensitivity and specificity to the TKLiaison assay for hematological malignancies. However, the AroCell TK 210 ELISA demonstrated a higher sensitivity for TK1 in sera from subjects with solid tumors and this may facilitate the application of TK1 as a biomarker for solid tumors. Furthermore, the robustness and convenience of the ELISA not only overcomes the limitations of TK-Liaison but also widens the clinical applications of TK1 in cancer management.
Citation Format: Jagarlamudi Kiran Kumar, Staffan Eriksson, Kerstin Hamberg Levedahl, Martin Höglund, Mojca Zupan, Joško Osredkar, Diana Cviič, Urska Furar. The assay of thymidine kinase 1 in sera from subjects with hematological and solid tumors with AroCell TK 210 ELISA: Comparison with TK-liaison assay and its clinical implications abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2232.
