In response to reactive oxygen species (ROS), thioredoxin and DJ-1 are upregulated to counteract the detrimental effect of ROS under normal condition. However, cancer cells can take advantage of thioredoxin and DJ-1 against ROS-induced cell damage. In several human cancer types, thioredoxin and DJ-1 were found to be overexpressed. The present study aimed to explore the serum levels of thioredoxin and DJ-1 in non-small cell lung cancer (NSCLC) patients and its relationship to the diagnosis and prognosis of this particular malignancy. Sera from 134 NSCLC patients and 168 healthy controls were obtained. Using the enzyme-linked immunosorbent assay (ELISA) method, the levels of serum thioredoxin and DJ-1 were measured and correlated to the clinicopathological characteristics of NSCLC patients. The diagnostic and prognostic significance of the biomarkers were evaluated by using receiver operating curve (ROC), Kaplan-Meier curve, and log-rank analyses and the Cox proportional hazard model, respectively. Serum thioredoxin and DJ-1 levels were significantly higher in the NSCLC patients than that in the controls (23.5 ± 6.57 vs. 13.8 ± 2.49 and 7.11 ± 2.02 vs. 5.18 ± 1.26, respectively). NSCLC patients at later stage cancer showed significantly higher levels of serum thioredoxin and DJ-1 than those at the early stages (P < 0.01 and P < 0.05, respectively). Multivariate logistic regression analysis showed that high serum thioredoxin level was an independent risk factor for lymph nodal metastases and distant metastases (OR = 2.18, 95 % CI 1.26-3.41 and OR = 3.68, 95 % CI 2.16-5.33, respectively). In addition, an increase in the serum DJ-1 level was also identified as an independent risk factor for nodal metastases (OR = 1.37, 95 % CI 1.11-3.04). For predicting the development of NSCLC, ROC/area under the curve (AUC) analysis for thioredoxin indicated an AUC of 0.80 (sensitivity 0.62, specificity 0.92), and ROC/AUC analysis for DJ-1 showed an AUC of 0.78 (sensitivity 0.66, specificity 0.89). NSCLC patients with high serum thioredoxin and DJ-1 levels had lower survival rates than those with low levels, and multivariate analyses for overall survival revealed that high serum thioredoxin levels served as an independent prognostic factor for NSCLC (HR = 2.07, 95 % CI 1.19-3.48). Serum levels of thioredoxin and DJ-1 were significantly higher in NSCLC patients; therefore, these may be utilized as novel diagnostic and prognostic biomarkers for NSCLC.
Keywords: DJ-1; Diagnosis; Non-small cell lung carcinoma; Overall survival; Prognosis; Thioredoxin.