Tumor Biology

, Volume 37, Issue 2, pp 1949–1958 | Cite as

Diagnostic and prognostic value of serum thioredoxin and DJ-1 in non-small cell lung carcinoma patients

Original Article

Abstract

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

Non-small cell lung carcinoma Thioredoxin DJ-1 Diagnosis Prognosis Overall survival 

Notes

Acknowledgments

We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript.

Conflicts of interest

None

Supplementary material

13277_2015_3994_Fig6_ESM.gif (35 kb)
Sup. Fig. 1

Comparison of serum thioredoxin (a) and DJ-1 (b) levels among different subgroups (adenocarcinoma, squamous cell carcinoma and other). (GIF 35 kb)

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High resolution image (TIFF 290 kb)
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Sup. Fig. 2

Serum thioredoxin (a, c) and DJ-1 (b, d) levels in NSCLC patients at different TNM stages (a, b for adenocarcinoma; c, d for squamous cell carcinoma; resepctively). (GIF 41 kb)

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High resolution image (TIFF 350 kb)
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Sup. Fig. 3

Serum thioredoxin (a, c) and DJ-1 (b, d) levels in OSCC patients with and without lymph nodal metastases (a, b for adenocarcinoma; c, d for squamous cell carcinoma; resepctively). (GIF 71 kb)

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High resolution image (TIFF 501 kb)
13277_2015_3994_Fig9_ESM.gif (65 kb)
Sup. Fig. 4

Serum thioredoxin (a, c) and DJ-1 (b, d) levels in OSCC patients with and without distant metastases (a, b for adenocarcinoma; c, d for squamous cell carcinoma; resepctively). (GIF 64 kb)

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High resolution image (TIFF 446 kb)
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Sup. Fig. 5

Receiver operating characteristic curves of serum thioredoxin (a, c) and DJ-1 (b, d) levels differentiating NSCLC patients from normal controls (a, b for adenocarcinoma; c,d for squamous cell carcinoma; resepctively). (GIF 59 kb)

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High resolution image (TIFF 350 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.The Third Department of TuberculosisShandong Chest HospitalJinanChina
  2. 2.Department of Radiology, Shandong Cancer Hospital and InstituteAffiliated to Shandong Academy of Medical ScienceJinanChina
  3. 3.Department of Thoracic Surgery, Jinan Central HospitalAffiliated to Shandong UniversityJinanChina
  4. 4.Department of Thoracic SurgeryJinan Central HospitalJinanChina

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