Relationship Between Thioredoxin Reductase Level And Short-term Efficacy & Prognosis Of Advanced Colorectal Cancer

Background and purpose:Colorectal cancer is one of the most common malignant tumors of the digestive system in the world.It is a serious public health issue that requires urgent attention.Colorectal cancer diagnosed in early stage is treated by surgical resection.However,in advanced stage,the disease is considered to be controlled by chemotherapy,targeted therapy,immunotherapy,and traditional Chinese medicine.During treatment,response is regularly evaluated by CT,MRI,etc.Biological markers could be a useful reference in clinical practice.The thioredoxin system is highly expressed in tumor tissues because it is reported to eliminate the reactive oxygen species produced in tumor immune microenvironment through a reduction reaction.Therefore,this study explores the correlation between the expression level of thioredoxin reductase(Trx R),the main component of the thioredoxin system,and the short-term efficacy and prognosis for patients with advanced colorectal cancer.Methods: This study collected baseline information(name,gender,age,hospitalization number)and clinical characteristics(TNM staging,primary site,pathological type,degree of differentiation)from all patients with advanced colorectal cancer who were treated in the Affiliated Tumor Hospital of Nanjing Medical University from July 2018 to January 2021.Plasma Trx R and CEA values of enrolled cases at baseline before treatment were recorded.The Trx R activity measurement sample is about 2.0 m L of the supernatant taken from the peripheral blood after centrifugation.The experimental material is Detection Kit for Thioredoxin Reductase(Trx R)Activity,and the method is spectrophotometry.The testing steps of Trx R include liquid preparation,sample addition,incubation,and detection.Finally,the value of of Trx R activity is reflected by detecting the amount of DTNB catalyzed by Trx R per unit time.After 2 cycles of anti-tumor therapy,plasma Trx R and CEA concentrations were also recorded.Therapeutic effect was evaluated according to the Response Evaluation Criteria in Solid Tumors.All enrolled patients were followed up to obtain the progression-free survival.All data are analyzed using IBM SPSS25.0.Results: A total of 141 patients with advanced colorectal cancer were enrolled in this study,and progressed at the end of the follow-up,while reaching the follow-up endpoint.There were 83 male patients and 58 female patients,ranging in age from 24 to 82 years and with a median age of 61 years.After 2 cycles of treatment,the response was evaluated.Forty seven cases obtained PR,and their plasma Trx R concentration after 2 cycles was lower than that before treatment,and the difference was statistically significant(P<0.001).Twenty one cases obtained PD,their mean plasma concentration of Trx R after 2 cycles was higher than the mean concentration before treatment,but the difference was not statistically significant(P=0.524).Kaplan-Meier univariate analysis of the prognosis of enrolled cases showed that low level of Trx R expression(Trx R≤8U/m L)before treatment is associated with a longer progression-free survival and better prognosis than those with high level of Trx R expression(Trx R>8U/m L),while the difference was statistically significant(7.0months vs 5.0 months,P=0.007).COX univariate regression analysis showed that the expression level of plasma Trx R before treatment was an independent risk factor for the progression of advanced colorectal cancer,HR=0.641,95%CI:(0.451～0.909),P=0.013.COX multivariate regression analysis also suggested the same conclusion,HR=0.564,95%CI:(0.389～0.818),P=0.003.Conclusion: The change of plasma Trx R concentration could be used to predict reponse of disease after treatment.Plasma Trx R expression level before treatment could be considered as a biological marker for predicting the prognosis of advanced colorectal cancer.