Correlation Of Mismatch Repair Protein Expression And Inflammatory Nutritional Markers With Endometrial Carcinoma

Objective: To investigate the expression loss of four mismatch repair proteins(MLH1,PMS2,MSH2 and MSH6)in tumor tissues in sporadic endometrial cancer and their correlation with clinicopathologic features and overall survival of patients.To explore the correlation between neutrophil/lymphocyte ratio(NLR),systemic immune inflammation index(SII),prognostic nutrition index(PNI),advanced lung cancer inflammation index(ALI),pathological features and overall survival of patients with endometrial cancer.Methods: A total of 218 patients with complete clinical,pathological,preoperative serological examination and follow-up information were included in a retrospective analysis of medical records of patients who were first diagnosed with endometrial cancer and underwent comprehensive staging surgery in the First Hospital of Lanzhou University from January 2018 to February 2022.The expression loss rate of four mismatch repair proteins was analyzed,and the relationship between protein expression loss and clinicopathological features and overall survival(OS)of patients was analyzed.The values of NLR,SII,ALI and PNI were calculated,and the best cutoff values were calculated by the most approximate entry index.218 patients were divided into high group and low group.Statistical methods were used to compare the differences in FIGO staging,muscle infiltration depth,vascular infiltration,histological type and overall survival between the high-value and lowvalue groups of NLR,SII,PNI and ALI in patients with endometrial cancer.For survival analysis of single group variable,Kaplan-Meier method was used to estimate the survival rate and Log-Rank method was used to test the distribution of survival curve for each group.The COX proportional risk regression model was used to further screen out the independent factors that had a significant impact on OS.Firstly,the single factor COX regression was used to screen out the significant influencing factors(P<0.1),and then the multi-factor COX regression was conducted.The correlation strength was represented by OR and 95%CI.Results:(1)Among the 218 patients with endometrial carcinoma,there were 164 cases in the MMR protein expression complete group(p MMR)and 54 cases in the MMR protein expression deletion group(d MMR),the deletion rate of MMR protein expression was 24.77%,among which the deletion rate of PMS2 was the highest.MLH1 was positively correlated with PMS2 deletion and MSH2 with MSH6 deletion(rs=0.856,P<0.001;rs=0.471,P<0.001),MLH1 and PMS2 were most common.There were statistically significant differences between p MMR group and d MMR group in fertility,menopause,vascular invasion,tissue differentiation degree in endometrioid adenocarcinoma,and invasion of lower uterine body(P<0.05).There were no significant differences in age,body mass index,diabetes mellitus,hypertension,tumor histological type,FIGO stage,and depth of muscle infiltration between the two groups(P>0.05).(2)In endometrial cancer,the risk of vascular invasion was higher in the group with high NLR and SII values;The risk of tumor myographic infiltration depth greater than 1/2 was higher in the high-value NLR group,and the difference between groups was statistically significant(P<0.05).(3)The group with low PNI and ALI values had a higher risk of vascular infiltration;FIGO stage II was more in the low ALI group,and the difference between groups was statistically significant(P<0.05).(4)Survival analysis showed that there was no statistical significance in median OS between d MMR group and p MMR group(17.4 months vs19.7 months,P>0.05).The OS of NLR<1.963 group was better than that of NLR≥1.963 group(19.93 months vs 16.99 months,P=0.014).The OS of SII<688.01 group was better than that of SII≥688.01 group(19.70 months vs 15.97 months,P=0.044).The OS of PNI≥55.95 group was better than that of PNI<55.95 group(18.30 months vs 18.17 months,P=0.043).There was no significant difference in median OS between ALI<46.97 group and ALI≥46.97 group(15.97 months vs 18.85 months,P=0.074).(5)COX univariate analysis showed that the risk factors for overall postoperative survival of patients with endometrial cancer were age,FIGO stage,degree of differentiation,histological type,vascular invasion,nerve invasion,muscular invasion,lower uterine body,NLR,SII,PNI,ALI;Multivariate analysis showed that the degree of tumor tissue differentiation,histological type,vascular invasion and nerve invasion were independent risk factors for overall postoperative survival of patients with endometrial cancer(P<0.05).Conclusion : 1.In endometrial cancer,the expression loss rate of mismatch repair proteins is relatively high,among which MLH1 and PMS2 expression loss is more common,and the co-expression loss of the two proteins is more common.2.The endometrial cancer patients with mismatch repair protein deficiency had atypical characteristics of infertility,obesity,hypertension,diabetes,and more postmenopausal patients;Its tumor tissue differentiation degree is worse,the tumor is easy to invade the lower uterine segment,more likely to appear tumor vascular invasion,nerve invasion.3.There was no correlation between loss of expression of mismatch repair protein and overall survival of patients with endometrial cancer;Higher NLR and SII and lower PNI were associated with shorter survival.4.Low tumor differentiation,non-endometrioid cancer,vascular invasion and nerve invasion are independent risk factors affecting the overall postoperative survival of patients with endometrial cancer.