Abstract
Gastric cancer (GC) is one of the leading malignancies around the world. Identification of novel and efficient biomarkers for GC diagnosis and evaluation of therapeutic efficiency could improve the therapeutic strategy in future clinical application. This study aims to evaluate the levels of plasma thioredoxin reductase (TrxR) activity in GC patients to confirm its validity and efficacy in GC diagnosis and evaluation of therapeutic efficiency. 923 cases were enrolled in the current study. In the group of GC patients before clinical intervention, plasma TrxR activity [9.09 (7.96, 10.45) U/mL] was significantly higher than in healthy controls [3.69 (2.38, 5.32) U/mL]. The threshold of TrxR activity for GC diagnosis was set at 7.34 U/mL with a sensitivity of 85.5% and a specificity of 97.9%. In GC patients after chemotherapy, plasma TrxR activity was remarkably higher in patients with progressive disease or uncontrolled condition [10.07 (8.19, 11.02) U/mL] compared with patients with complete or partial response [7.12 (6.08, 8.37) U/mL] in response to chemotherapy. TrxR activity displayed the higher efficiency to distinguish between GC patients with two distinct clinical outcomes than carcinoembryonic antigen (CEA), cancer antigen 72-4 (CA72-4) and cancer antigen 19-9 (CA19-9). Moreover, combination of TrxR, CEA, CA72-4 and CA19-9 was demonstrated to be more effective in both GC diagnosis and evaluation of therapeutic efficiency than was each biomarker individually. Together, plasma TrxR activity was identified as a novel and efficient biomarker of GC, both in diagnosis and monitoring of therapeutic efficiency in response to chemotherapy.
Highlights
Gastric cancer (GC) is one of the leading malignancies around the world
thioredoxin reductase (TrxR) was reported to be overexpressed in BGC823 GC cell line, and the inhibition of TrxR activity by the TrxR-specific inhibitor resulted in a robust antitumor effect in BGC823 cell line as well as in vivo in GC xenograft mice, suggesting that TrxR may be a potential biomarker involved in the GC diagnosis and evaluation of therapeutic efficiency[39,40]
A total of 923 specimens were recruited in the current study, including 131 specimens from patients with GC before clinical intervention, 662 specimens from patients with GC after chemical drug treatment, and 130 healthy controls
Summary
Gastric cancer (GC) is one of the leading malignancies around the world. Identification of novel and efficient biomarkers for GC diagnosis and evaluation of therapeutic efficiency could improve the therapeutic strategy in future clinical application. Plasma TrxR activity was identified as a novel and efficient biomarker of GC, both in diagnosis and monitoring of therapeutic efficiency in response to chemotherapy. Invasive diagnostic strategies such as gastroscope are widely applied in the clinical diagnosis of GC These tests usually fail to uncover the hidden or subclinical lesions and lead to high false-positive rates especially in early-stage GC8. Previous studies have suggested TrxR as a potential and effective clinical biomarker of early-stage diagnosis and prognosis after chemotherapy in NSCLC, breast cancer, prostate cancer and liver cancer[35,36,37,38]. We conducted a retrospective study aiming to analyze the efficiency of TrxR activity as a plasma biomarker in the GC diagnosis and evaluation of therapeutic efficiency. Our results revealed that TrxR could be a valuable biomarker of GC diagnosis and therapeutic evaluation for future clinical application
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