Thymidine kinase 1 concentration in pleural effusion is a diagnostic marker and survival predictor for malignant pleural effusion

Abstract

Objective Thymidine kinase 1 (TK1) is a key enzyme in the pyrimidine salvage pathway. Increased TK1 concentration correlates with cell division. TK1 is an emerging biomarker in cancer diagnosis; however, its effectiveness in diagnosis and management for malignant pleural effusion (MPE) is unclear. We evaluated the diagnostic efficiency and prognostic value of pleural effusion TK1 (pTK1) concentration for MPE. Methods From 2013 to 2017, 210 pleural effusion samples were collected from 160 patients diagnosed with MPE and 50 patients diagnosed with benign pleural effusion (BPE). TK1 concentrations in pleural effusion were measured by chemiluminescence dot blot assays. The median follow‐up was 12 months. We constructed a receiver‐operating characteristic (ROC) curve to find the optimal cutoff value for MPE diagnosis. The hazard ratios were estimated using a multivariable Cox proportional hazard model. A nomogram was drawn to illustrate the prognostic characteristics of MPE. Results The TK1 concentration in pleural effusion was significantly higher in MPE than BPE (P < 0.001), and patients with MPE could be distinguished by an optimal cutoff value of 3.10 pmol/L with a sensitivity of 0.894 and a specificity of 0.800. The multivariate analysis suggested that pTK1 concentration was an independent predictor of survival in patients with MPE. Conclusions The diagnostic and prognostic prediction of MPE may be improved by measuring pTK1 concentration and utilizing a multivariate nomogram.

Development and External Validation of a Nomogram for Predicting Cancer-Specific Survival of Non-Small Cell Lung Cancer Patients With Ipsilateral Pleural Dissemination

“…Recently, several predictive models for patients with malignant pleural effusion or malignant pleural pericardial effusion had been published. Most of them focused on the concentration of biomarkers in the pleural effusion or serum (33)(34)(35); however, the higher cost and the variation of result owing to the different techniques (36), as well as the difficulty in collecting extra tissues in patients with poor physical condition, limited the application of these predictive models (37). Tian et al used the data of NSCLC patients with malignant pleural effusion or pericardial effusion from SEER database between 2010 and 2015 to developed a nomogram, which included age, gender, race, primary site, histology type, TN status, and effusion patterns with a C-index of 0.736 (38).…”

“…Recently, several predictive models for patients with malignant pleural effusion or malignant pleural pericardial effusion had been published. Most of them focused on the concentration of biomarkers in the pleural effusion or serum ( 33 – 35 ); however, the higher cost and the variation of result owing to the different techniques ( 36 ), as well as the difficulty in collecting extra tissues in patients with poor physical condition, limited the application of these predictive models ( 37 ). Tian et al.…”

Nomogram construction for predicting survival of patients with non‑small cell lung cancer with malignant pleural or pericardial effusion based on SEER analysis of 10,268�patients

“…Several predictive models for survival in MPE or MPCE have been published; however, a number of these are based on biomarker concentrations in the serum and/or in the effusion (6,7,16). In addition to the difficulty in accessing a sufficient effusion sample in patients with a poor physical status or a low effusion volume, the biomarker concentration in a sample can vary due to different measurement techniques (17).…”

Thymidine kinase 1 through the ages: a comprehensive review

“…Furthermore, tissue staining for TK1 has been used to identify activated tumor vessels involved in angiogenesis in colorectal cancer (CRC) patients; indeed, in studies involving double immunostaining for both CD31 and TK1, results showed TK1 to be a highly specific marker for activated vessels [ 106 ]. Tian et al [ 107 ] demonstrated the diagnostic and prognostic capabilities of TK1 concentrations over those of other biomarkers in malignant pleural effusion (MPE), especially when compared to parallel biomarker readings of benign pleural effusion (BPE). Within their study, Tian et al compared pleural TK1 to the measurement of serum TK1 levels in 210 patients whose samples were classified as MPE or BPE.…”