Plasma activity of Thioredoxin Reductase as a Novel Biomarker in Gastric Cancer

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.

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

“…[157] TRXR activity is significantly higher in the plasma of gastric cancer patients compared to healthy controls. [180] Hepatocellular carcinoma TRX expression is overexpressed in HCC compared to the control group.…”

Clinical application of thioredoxin reductase as a novel biomarker in liver cancer

“…Thioredoxin reductase (TrxR) is a NADPH-dependent dimeric selenide containing FAD domains. Numerous studies have shown that levels of TrxR are significantly higher than those of CEA and CA19-9 in malignant diseases such as breast, lung, and colorectal cancers 34 , 58 . In addition, TrxR has shown great therapeutic value in malignant diseases such as renal and lung cancer, and the combined sensitivity of TrxR compared with conventional tumor markers alone seems to be superior 34 .…”

“…Previous studies suggested that TrxR indicates higher levels of abnormally proliferating cells, and may have a superior diagnostic efficacy than other conventional tumor markers. In addition, TrxR activity is rapidly downregulated after chemotherapy in non-small cell lung cancer (NSCLC), gastric cancer, and breast cancer [33][34][35] . Previous studies consistently demonstrated that TrxR has potentially high value for clinical diagnosis and assessment of therapeutic efficacy.…”

Discovery of hydroxytyrosol as thioredoxin reductase 1 inhibitor to induce apoptosis and G1/S cell cycle arrest in human colorectal cancer cells via ROS generation

“…As both Trx and TrxR1 have been reported to be upregulated in numerous human cancer types, including leukemia, lung cancer, breast cancer and colorectal cancer among others, and be associated with increased tumor growth, drug resistance and poor patient prognosis, the thioredoxin system has been recognized as an attractive target for anticancer drug development (4,(6)(7)(8)(9)(10)40). This system plays a role in maintaining H 2 O 2 levels in cells via the conversion of H 2 O 2 to H 2 O. Trx contains two adjacent thiols in its reduced form that are converted to a disulfide bond in the oxidized form (39).…”

“…Mammalian thioredoxin (Trx) reductase 1 (TrxR1) is a selenoprotein that functions to maintain redox homeostasis in cells via transferring electrons from NADPH to its substrate Trx (4,5). Both Trx and TrxR1 are reported to be upregulated in CRC cells and have been associated with poor prognosis and resistance to chemotherapy (6)(7)(8)(9). Increasing evidence has suggested that TrxR1 is involved in multiple steps of tumorigenesis (10)(11)(12)(13)(14).…”