Abstract

There is an increased demand for efficient biomarkers for the diagnosis of non-small cell lung cancer (NSCLC). This study aimed to evaluate plasma levels of TrxR activity in a large population to confirm its validity and efficacy in NSCLC diagnosis. Blood samples were obtained from 1922 participants (638 cases of NSCLC, 555 cases of benign lung diseases (BLDs) and 729 sex- and age-matched healthy controls). The plasma levels of TrxR activity in patients with NSCLC (15.66 ± 11.44 U/ml) were significantly higher (P < 0.01) than in patients with BLDs (6.27 ± 3.78 U/ml) or healthy controls (2.05 ± 1.86 U/ml). The critical value of plasma TrxR activity levels for diagnosis of NSCLC was set at 10.18 U/ml, with a sensitivity of 71.6% and a specificity of 91.9%. The combination of NSE, CEA, CA19-9, Cyfra21-1, and TrxR was more effective for NSCLC diagnosis (sensitivity and specificity in the training set: 85.6%, 90.2%; validation set: 86.2%, 92.4%) than was each biomarker individually (P < 0.001). TrxR can also efficiently distinguish the metastatic status of the tumor, and it can further differentiate between various histological differentiations. Together, plasma TrxR activity was identified as a convenient, non-invasive, and efficient biomarker for the diagnosis of NSCLCs, particularly for discriminating between metastatic and non-metastatic tumors, or for histologic differentiation.

Highlights

  • Lung cancer is one of the most common malignancies and the most frequent cause of cancer-related death[1]

  • In our previous retrospective investigation, we evaluated a small cohort of patients with non-small cell lung cancer (NSCLC) (43 cases), revealing that plasma levels of Thioredoxin reductase (TrxR) activity were significantly higher in these patients than in healthy controls

  • Overexpression of TrxR has been observed in multiple types of tumor according to previous literature and NCI-60 screening, a panel of 60 human cancer cell lines used by NCI to detect potential anticancer activity[22,32,33,47,48,49]

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Summary

Introduction

Lung cancer is one of the most common malignancies and the most frequent cause of cancer-related death[1]. At present, imaging techniques such as computed tomographic (CT) scans and chest X-rays play an important role in the clinical diagnosis of lung cancer These tests have high false-positive rates and usually fail to uncover the hidden or subclinical lesions or small metastases, resulting in their limited application[16]. Thioredoxin reductase (TrxR) is a component of several redox-sensitive signaling cascades that mediate specific physiological processes, including those relating to cell survival, maturation, growth, migration, and inhibition of apoptosis[22,23,24,25,26,27] This protein attracted our attention because it plays a key role in the tumor-related redox process[28].

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