Serological Thymidine Kinase 1 is a Biomarker for Early Detection of Tumours—A Health Screening Study on 35,365 People, Using a Sensitive Chemiluminescent Dot Blot Assay

Abstract

Serological thymidine kinase 1 (STK1) is a reliable proliferation marker for prognosis, monitoring tumour therapy, and relapse. Here we investigated the use of STK1 in health screening for early detection of pre-malignant and malignant diseases. The investigation was based on 35,365 participants in four independent health screening studies in China between 2005–2011. All participants were clinically examined. The concentration of STK1 was determined by a sensitive chemiluminescent dot blot ECL assay. The ROCvalue of the STK1 assay was 0.96. At a cut-off STK1 value of 2.0 pM, the likelihood (+) value was 236.5, and the sensitivity and the specificity were 0.78 and 0.99, respectively. The relative number of city-dwelling people with elevated STK1 values (≥2.0 pM) was 0.8% (198/26,484), while the corresponding value for the group of oil-field workers was 5.8% (514/8,355). The latter group expressed significantly higher frequency of refractory anaemia, fatty liver, and obesity, compared to the city dwellers, but no cases of breast hyperplasia or prostate hyperplasia. Furthermore, people working in oil drilling/oil transportation showed higher STK1 values and higher frequency of pre-malignancies and benign diseases than people working in the oil-field administration. In the STK1 elevated group of the city-dwelling people, a statistically significantly higher number of people were found to have malignancies, pre-malignancies of all types, moderate/severe type of hyperplasia of breast or prostate, or refractory anaemia, or to be at high risk for hepatitis B, compared to people with normal STK1 values (<2.0 pM). No malignancies were found in the normal STK1 group. In the elevated STK1 group 85.4% showed diseases linked to a higher risk for pre-/early cancerous progression, compared to 52.4% of those with normal STK1 values. Among participants with elevated STK1 values, 8.8% developed new malignancies or progress in their pre-malignancies within 5 to 72 months, compared to 0.2% among people with normal STK1 values. People who showed elevated STK1 values were at about three to five times higher risk to develop malignancies compared to a calculated risk based on a cancer incidence rate of 0.2–0.3%. We conclude that serological TK1 protein concentration is a reliable marker for risk assessment of pre/early cancerous progression.

The Thymidine Kinase-1(tk-1) as a Potential Tumor Marker: Serum Levels in Serum of Patients With Solid and System Malignance Neoplasms

“…Была доказана значимость ТК-1 (концентрации в СК) как маркера риска наличия предраковых заболеваний и раз-вития ЗНО: при ДУ 2,0 пмоль/л чувствительность и специ-фичность составили 78% и 99% соответственно, а значе-ние AUC -0,96 [65].…”

Thymidine Kinase 1: A Universal Marker for Cancer

“…For example, TK1 has been established as a serum biomarker in breast cancer, lung cancer, colon cancer, malignant melanoma, gastric cancer, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, and acute myeloid leukemia in addition to several other cancer types (Li et al, 2010;Liu et al, 2011;O'Neill, Zhang, Li, Fuja, & Murray, 2007;Wu et al, 2013;Xu et al, 2009). TK1 is elevated in the very early stages of cancer and has even been found elevated in the precancerous stages (S. Huang et al, 2011). In fact, in a health screen of 35,365 individuals 0.8% had elevated serum TK1, and 8.8% of those with elevated TK1 went on to develop new malignancies or had progression of their pre-malignancies (Chen et al, 2011).…”

“…TK1 is elevated in the very early stages of cancer and has even been found elevated in the precancerous stages (S. Huang et al, 2011). In fact, in a health screen of 35,365 individuals 0.8% had elevated serum TK1, and 8.8% of those with elevated TK1 went on to develop new malignancies or had progression of their pre-malignancies (Chen et al, 2011). Recent studies have also found that TK1 shows similar trends in tumors.…”

Serum thymidine kinase 1 is a reliable maker for the assessment of the risk of developing malignancy: A case report

“…These types of tests were performed annually between 2007 and 2014 (83 months). The STK1p assay was performed using a commercial kit, based on an enhanced chemiluminescence dot blot assay (SSTK Biotech Ltd., Shenzhen, China) (13). Briefly, 3 µl serum were directly applied onto a nitrocellulose membrane.…”

“…Serum TK1 protein (STK1p) level, determined by non-invasive serological methods, was found to be an emerging potential cell proliferation biomarker for the prognosis of cancer patients (7)(8)(9), for monitoring tumor treatments, relapse, follow-up and survival, and particularly for the early detection of cancer development risk (10,11). A sensitive chemiluminescence dot blot assay of STK1p was developed by the Swedish TK1 Research Team in 2000 (7,9), which has become a commercial kit (Sino-Swed Biotech Ltd., Shenzhen, China) for the early detection of pre/early risk of developing cancer in health screening (1,2,12 (13). The current study presents the case of a patient that exhibited a higher risk of developing malignancies for three types of diseases.…”