| [Background]Indoleamine 2,3-dioxygenase 1(IDO1)is an important rate-limiting enzyme in the metabolic pathway of tryptophan(L-TRP).High expression of IDO1 can promote tryptophan metabolism and induce its downstream products to play immunomodulatory roles,thus leading to tumor immune escape.Current studies on IDO1 focus on embryonic development,inflammatory response,malignant tumors and so on.There are few studies in colorectal cancer and its clinical value needs to be further explored.At the same time,the need for adjuvant therapy after stage Ⅱ colorectal cancer surgery is controversial,and there are great differences in the improvement of patients’ prognosis.[Objective]To investigate the effect of IDO1 expression on disease-free survival(DFS)and pathologic complete response rate(PCR)in neoadjuvant chemoradiotherapy patients with rectal cancer.[Methods]To analyze the expression of IDO1 in the public database TCGA(The Cancer Genome Atlas)and its relationship with prognosis.At the same time,the department of colorectal surgery were retrospectively analyzed from 2013 to 2014 enrolled patients with colorectal cancer,and screening according to the results of the postoperative pathological stage Ⅱ(T3-T4N0M0)information of 397 patients with colorectal cancer,clinical pathologic information statistics,and cancer and normal tissue wax block,made into tissue microarray IDO1 immunohistochemical high-throughput analysis,follow-up of the survival of patients after treatment.SPSS21.0 statistical software was used to analyze the clinicopathological information.IDO1 immune score and patient survival.[Results]Analysis of TCGA data showed that IDO1 expression was higher in cancer tissues,and increased in colorectal cancer tissues with later stages,and was negatively correlated with prognosis.Our study found that the positive expression rate of IDO1 immunohistochemistry in stage Ⅱ colorectal cancer tissues was 67.5%,and the corresponding expression rate in normal tissues was 24%.In univariate analysis,high expression of IDO1 was associated with carcinoembryonic antigen(CEA),tumor location,tumor pathological subtype,perineuronal invasion and vascular carcinoma embolism before operation.Further,bivariate logistic regression analysis showed that tumor location,tumor pathological subtype.perineuronal invasion and vascular carcinoma embolism were independent risk factors affecting the high expression of IDO1.Furthermore,Kaplan-Meier survival curve was used to analyze the correlation between disease-free survival(DFS)and perineuronal invasion,vascular carcinoma embolism,T stage and IDO1 expression.Cox regression analysis showed that perineuronal invasion,T stage and IDO1 expression were independent risk factors affecting DFS.Kaplan-Meier survival curve analysis showed that vascular carcinoma thrombus,nerve invasion,microsatellite status and IDO1 expression were correlated with overall survival(OS).Further Cox regression analysis showed that IDO1 expression was an independent risk factor affecting overall survival.Further stratification showed that the high expression of IDO1 might affect DFS after adjuvant therapy for stage Ⅱ colorectal cancer,while the low expression of IDO1 did not.[Conclusions]The higher expression of IDO1 in stage Ⅱ colorectal cancer tissue suggests a greater risk of immune escape.The high expression of IDO1,T stage,perineuronal invasion and other pathological factors can be used as the prognostic factors.The expression of IDO1 can provide reference for the need of adjuvant therapy after stage Ⅱcolorectal cancer surgery.[Background]From the epidemiological point of view,the majority of rectal cancer patients in China are at local progression stage.Preoperative neoadjuvant concurrent chemoradiotherapy can effectively reduce the size of local invasive tumors,control the progression of local tumors,improve disease-free survival(DFS)and improve postoperative tumor regression grade(TRG).At present,the treatment mode of radical surgery for colorectal cancer after preoperative neoadjuvant chemoradiotherapy has become the standard regimen for the treatment of locally advanced colorectal cancer in many medical centers,and the value of local immune response to the prognosis of patients with colorectal cancer has been widely confirmed.Neoadjuvant chemoradiation important effects on the tumor local immune response,IDO1 is the key enzyme of tryptophan metabolic pathways,catalytic tryptophan catabolism of downstream products of inhibitory effects on the local immunity,so that the tumor escape,lead to the further progress of tumor and metastasis,the curative effect of neoadjuvant chemoradiation also depends on local tumor immune environment.The high expression of IDO1 has been proved to be associated with poor prognosis in many studies,but the role of its expression in the prognosis of neoadjuvant rectal cancer patients is still unclear,and its mechanism needs to be further confirmed.[Objective]In this study,a total of 327 patients with stage Ⅱ or Ⅲ advanced rectal cancer who underwent surgery after neoadjuvant chemoradiotherapy in our medical center from November 2014 to August 2017 were collected for clinicopathological data,and their survival was followed up.At the same time.the tissue wax pieces of 327 patients were made into tissue chips for further IDO1 immunohistochemical analysis.Finally,231 patients with complete data were analyzed and studied.According to IDO1 immunohistochemical score(0-6 was classified as low expression.7-12 was classified as high expression),they were divided into high expression group and low expression group:Low expression group 117 cases(50.6%).high expression group 114 cases(49.3%).In this study,disease-free survival and pathological response rate were analyzed as the primary endpoints,and postoperative overall survival was taken as the secondary end points.[Results]Among 231 patients,IDO 1 immunohistochemical analysis showed low expression in 117 patients(50.6%)and high expression in 114 patients(49.3%)after neoadjuvant therapy(7-12 points).In this study,univariate analysis combined with multivariate regression analysis was used to analyze the clinical characteristics,pathological parameters and tumor prognosis of the patients.The rate of pathological complete regression(pCR)was 10.8%(n=29)in the group with low expression of IDO1,and 4.8%(n=11)in the group with high expression of IDO1.There was a significant difference between the two groups(P=0.002).There were differences in preoperative CEA and pathological T stage between the two groups(P=0.004 and P=0.002),while there were no statistically significant differences in other clinicopathological data.Further multivariate analysis showed that IDO1 expression was an independent factor affecting the pathologic complete response’ rate(P=0.029;OR=0.418;95%CI:0.191-0.913),and it was also demonstrated that high IDO1 expression was independently associated with increased preoperative CEA and increased local recurrence rate.Kaplan-Meier analysis and Cox regression analysis showed that IDO1 expression was a significant independent prognostic factor affecting disease-free survival(P=0.003;OR=0.45;95%CI:0.264-0.768),but IDO1 expression had no effect on overall survival(P=0.093,OR=0.544,95%CI:0.267-1.108).[Conclusions]High expression of IDO1 is an important factor to resist the occurrence of pathological complete response rate.Meanwhile,high expression of IDO1 reduces disease-free survival and is more prone to local recurrence. |
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