Patients with esophageal cancer are often diagnosed at advanced stages, leading to poor prognosis. Biomarkers are needed to enable earlier detection as well as to aid in the prediction of prognosis, but to date these tools remain scarce. Thymidine kinase (TK1) has been shown to exhibit altered expression levels in esophageal tumor cells, therefore this study sought to determine whether serum TK1 levels are also altered and, if so, to assess the utility of TK1 as a biomarker in esophageal squamous cell carcinoma. Eighty patients with esophageal squamous cell carcinoma were included as the case group and 80 healthy persons were selected as the control group. Serum TK1 levels, postoperatively for cancer patients, were detected by chemiluminescence. Follow-up was performed for cancer patients to determine the progression free survival (PFS) and overall survival (OS). Serum TK1 levels were significantly higher in cases of esophageal cancer than in healthy control individuals (t=7.235, P<0.05). When cancer cases were sub-divided into lower and higher serum TK1 levels, based on the mean level of 3.38 pmol/L, statistically significant differences in TNM stage, tumor differentiation, and lymph node metastasis were observed between patients with ≥3.38 pmol/L and <3.38 pmol/L (χ(2)=28.134, 3.187, 7.234, P<0.05). The average OS of all esophageal cancer patients was 30.13 months, and the average PFS was 24.73 months. However, when the cases were divided by serum TK1 level, average OS of those with higher serum TK1 (≥3.38 pmol/L) was significantly lower (23.98 mo) than those with lower serum TK1 (32.96 mo) (χ(2)=5.439, P<0.05). Similarly, average PFS was significantly lower in patients with higher serum TK1 (17.65 mo versus 27.62) (χ(2)=4.640, P<0.05). OS was correlated with TNM stage (hazard ratio, HR=3.116), degree of tumor differentiation (HR=0.427), lymph node metastasis (HR=0.535), and serum TK1 level (HR=1.913) (Wald χ(2)=6.782, 6.228, 4.562, 5.681, P<0.05). Similarly, PFS was correlated with TMN stage (HR=2.153), degree of tumor differentiation (HR=0.627), and serum TK1 level (HR=1.632) (Wald χ(2)=7.035, 5.335, 4.887, P<0.05). Thus, patients with esophageal squamous cell carcinoma exhibit higher circulating TK1 levels, consistent with findings of increased TK1 expression in tumor cells. Further, the correlation of serum TK1 levels with clinical features of esophageal cancer and with patient survival suggest that serum TK1 may serve as a valuable biomarker for predicting patient prognosis.
Keywords: Thymidine kinase 1; esophageal squamous cell carcinoma; prognosis; serological detection; survival analysis.