Serum thymidine kinase 1 reflects the progression of pre-malignant and malignant tumors during therapy

Abstract

Abstract. This study evaluated the clinical utility of serum thymidine kinase 1 (STK1) in following the progression of pre-malignancies and malignancies and in monitoring the response of common carcinomas to therapy within a routine clinical setting. The STK1 concentration levels of patients with malignancies (n=224), pre-malignancies (n=10), non-tumor/ non-proliferating diseases (systemic lupus erythematosus, SLE) (n=53), benign tumors (n=20) and healthy volunteers (n=761) were determined by enhanced chemoluminescence dot blot assay. Prior to treatment, STK1 levels in the pre-malignant group alone (3.1±2.3) or in the pre-malignant and malignant groups together (2.3±1.9) were significantly higher than in the benign (1.4±0.8), SLE (1.1±0.8) or healthy volunteer (0.6±0.4) groups (p<0.01). According to ROC analysis, the STK1 assay provided a high degree of discrimination between STK1-positive pre-malignant (0.978) or pre-malignant + malignant (0.941) patients and STK1-negative healthy individuals. After varying treatments (surgery, chemotherapy, X-ray), STK1 levels increased by 40-50% during the first month, then decreased back to normal values or even lower. Following treatment, STK1 levels were significantly increased in squamous cell carcinoma (SCC) as compared to adenocarcinoma (AC) patients. In other types of malignancies, STK1 levels decreased from as early as the first month. The STK1 levels of relapsed treated patients were significantly higher (50-60%) than those of mid/long-term treated patients. In conclusion, the STK1 assay discriminated between patients with malignancies and healthy individuals very well, and is therefore potentially useful for a broad range of clinical applications. For example, it could be used for the evaluation of early tumor progression or of tumor progression during therapy in routine clinical settings, as well as for the screening of healthy individuals.

Thymidine kinase 1 as a diagnostic tumor marker is of moderate value in cancer patients: A meta-analysis

“…It is evident that two studies are out of the range of sensitivity. These are Xu et al (33) and McKenna et al (38).…”

“…carcinomas (12,34), 1 lung (35), 1 ovarian (42) and 1 head and neck cancer (31). Six studies used CLIA (12,19,(33)(34)(35)(36), five studies used REA (32,(41)(42)(43)(44) and two studies used ELISA (37,38) and two studies used IHC (37)(38)(39)41). The characteristics of the selected studies are summarized in Table I.…”

“…1). Among these, 12 investigated solid tumors (8,12,(32)(33)(34)(35)(36)(37)(38)(39)(40)42,44) and included 1,538 patients and 1,484 controls and 3 investigated non-solid tumors (19,40,42) and included 302 patients and 180 controls. The solid tumors included 7 breast carcinomas (33,35-39,43), 2 renal Funnel plot of sensitivity and specificity of thymidine kinase.…”

“…After reviewing the titles and abstracts of the 493 studies, 478 were excluded: 40 due to repetition, 190 recruited patients in whom TK1 was detected following chemotherapy or surgery, the full text was unavailable for 50 studies and 198 studies were not conducted on human subjects. A total of 15 eligible studies involving 1,840 patients and 1,664 controls were included in the pooled analyses (12,19,(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44) (Fig. 1).…”

“…9) and it suggested that all studies came from a single population (30). [Xu et al (33) and McKenna et al (38)]. One of these used the chemiluminescence immunoassay (CLIA) and the other one the enzyme-linked immunosorbent assay (ELISA) method.…”