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.

Figure 1

Scatter plot of the distribution of plasma TrxR (A), serum CEA (B), serum CA19-9 (C), and serum CA72-4 (D) levels in GC patients and healthy controls. The black horizontal lines are median values and interquartile ranges. P values were determined by the Mann–Whitney U test.

Figure 2

(A,B) ROC curve analyses of TrxR, CEA, CA19-9, CA72-4 (A), and the combinations thereof (B) for the differentiation of GCs and healthy controls. (C–F) Scatter plot of the distribution of plasma TrxR (C), serum CEA (D), serum CA19-9 (E), and serum CA72-4 (F) levels in GC patients with various pathological TNM stages. The black horizontal lines are median values and interquartile ranges. P values were determined by the Mann–Whitney U test. N.S: no statistical significance.

Figure 3

(A) Scatter plot of the distribution of plasma TR activity levels between GC patients before clinical interventions and GC patients after chemotherapy. (B–E) Scatter plot of the distribution of plasma TrxR (B), serum CEA (C), serum CA19-9 (D), and serum CA72-4 (E) among GC patients with different clinical outcome after chemotherapy (CUP vs. CRP). CUP: clinical unresponsive patient; CRP: clinical responsive patient. The black horizontal lines are median values and interquartile ranges. P values were determined by the Mann–Whitney U test. N.S: no statistical significance.

Figure 4

(A,B) ROC curve analyses of TrxR, CEA, CA19-9, CA72-4 (A), and the combinations thereof (B) for the differentiation of GCs with different clinical outcome after chemotherapy (CUPs vs. CRPs). (C–E) Pearson correlation analyses between TrxR activity with CEA (C), CA19-9 (D), CA72-4 (E) levels in GC patients after chemotherapy. P values were determined by the Spearman test.