Plasma Thioredoxin Reductase as a Potential Biomarker for Gynecologic Cancer

Abstract

Background: According to previous literatures, plasma thioredoxin reductase (TrxR) level was significantly elevated in various malignant tumors and serve as a potential biomarker for diagnosis and prognostic prediction. However, there is little awareness of the clinical value of plasma TrxR in gynecologic malignancies. In the present study, we aim to evaluate the diagnostic accuracy of plasma TrxR in gynecologic cancer and explore its role in treatment surveillance.

Methods: We retrospectively enrolled 134 patients with gynecologic cancer and 79 patients with benign gynecologic disease. The difference of plasma TrxR activity and tumor markers level between two groups was compared using Mann-Whitney U test. By detecting pretreatment and post-treatment level of TrxR and conventional tumor markers, we further assessed the change trend of them with the Wilcoxon signed-ranks test.

Results: Compared with benign control [5.7 (5, 6.6) U/mL], statistically significant increase of TrxR activity was observed in gynecologic cancer group [8.4 (7.25, 9.825) U/mL] (P < .0001), regardless of age and stage. On the basis of receiver operating characteristic (ROC) curves, we found plasma TrxR shows the highest diagnostic efficacy for distinguishing malignancy with benign disease, with an area under the curve (AUC) of 0.823 (95% confidence interval [CI] = 0.767-0.878), in the whole cohort. Besides, patients receiving treatment previously [8 (6.5, 9) U/mL] had a decreased TrxR level relative to treatment-native patients [9.9 (8.6, 10.85) U/mL]. Furthermore, follow-up data showed that plasma TrxR level would be evidently decreased after two courses of antitumor therapy (P < .0001), which is consistent with the downward trend of conventional tumor markers.

Conclusion: Collectively, all these results demonstrated plasma TrxR is an effective parameter for gynecologic cancer diagnosis and concurrently acts as a promising biomarker for treatment response assessment.

Keywords: biomarker; diagnosis; gynecologic cancer; prognosis; thioredoxin reductase.

Figure 1.

The difference of plasma TrxR activity and routine tumor markers level in benign gynecologic disease and gynecologic cancer. (A) Scatter plot of the distribution of plasma TrxR, (B) serum AFP, (C) serum CEA, (D) serum CA199, (E) serum CA125, and (D) serum CA153 levels in benign controls and gynecologic cancer. The black horizontal lines are median values and interquartile ranges. P values were determined by the Mann-Whitney U test (*P < .05, **P < .01, ***P < .001, ****P < .0001). Abbreviations: AFP, alpha-fetoprotein; AUC, area under curve; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; ns, no statistical significance; TrxR, thioredoxin reductase.

Figure 2.

ROC curves of TrxR and routine tumor markers for gynecologic cancer versus benign controls. (A) ROC curves of TrxR, CA125 and the combinations thereof. (B) ROC curves of TrxR, CA153 and the combinations thereof. (C) ROC curves of TrxR, CA125, CA153, and the combinations thereof. (D) ROC curves of TrxR, AFP, CEA, CA199, CA125, CA153, and the combinations thereof. Abbreviations: AFP, alpha-fetoprotein; AUC, area under curve; CA, carbohydrate antigen; CEA, carcinoembryonic antigen; ROC, receiver operating characteristic; TrxR, thioredoxin reductase.

Figure 3.

The correlation of plasma TrxR activity and treatment in gynecologic cancer patients. (A) Scatter plot of the distribution of plasma TrxR in benign controls, treatment-experienced, and treatment-naïve gynecologic cancer patients. (B) Plasma TrxR activity of gynecologic cancer patients based on different therapies. (C) The change trend of plasma TrxR after platinum/taxane-based or targeted therapy. Abbreviation: TrxR, thioredoxin reductase.