Study On Microsatellite Instability And Related Gene Mutation Of Rectal Cancer And The Sensitivity Of Radiotherapy

Background:Rectal cancer is one of the most serious gastrointestinal malignancies threatening human health and safety.However,in patients with local progression,not only is surgery more difficult and local recurrence rate higher,but also the possibility of retaining anal sphincter is less,and the quality of life will be greatly affected.Neoadjuvant concurrent chemoradiotherapy combined with surgery has gradually become the standard treatment for locally advanced rectal cancer patients.However,some patients have poor sensitivity to radiotherapy and cannot benefit from it.Therefore,it is important to explore the predictors of neoadjuvant radiotherapy sensitivity in colorectal cancer.At present,there are existing literature reports that Microsatellite instability(MSI)and PIK3 CA gene mutation are positively correlated with radiotherapy sensitivity of rectal cancer,EGFR gene mutation is negatively correlated with radiotherapy sensitivity,and KRAS gene mutation is unrelated to it.Objective:This study was to explore the MSI and PIK3 CA,EGFR,KRAS mutations and colorectal cancer neoadjuvant radiotherapy sensitivity relationship,MSI characteristic as well as PIK3 CA gene expression in the crowd,EGFR gene,the relationship between KRAS mutations respectively with MSI,in the hope of looking for rectal cancer neoadjuvant radiotherapy sensitivity predicted markers to better implement individualized comprehensive treatment in patients with locally advanced rectal cancer.Methods:The case data of 76 patients with stage IIB and III rectal cancer who received treatment in the affiliated hospital of Qingdao university from September 2016 to August 2018 were included in this retrospective study.All patients accepted neoadjuvant chemoradiation,after 3 weeks comprehensive review to determine whether a surgical indications,the subgroup of patients with surgical indications of six to eight weeks after the end of the neoadjuvant therapy surgery treatment,to observe the postoperative specimens reach pathological complete response(pathological complete response,pCR)the clinical characteristics of patients.At the same time,samples obtained by electronic colonoscopy before radiotherapy in patients who completed neoadjuvant therapy were tested for MSI,EGFR,PIK3 CA and KRAS genes,to analyze the relationship between the above gene mutations and clinical characteristics and pCR,as well as the relationship between MSI and EGFR,PIK3 CA and KRAS gene mutations,respectively.SPSS 23.0 statistical software was used for x2 test and logistic multivariate regression analysis,and p < 0.05 was considered statistically significant.Results:1.75 patients completed neoadjuvant concurrent chemoradiotherapy,and 1 patient was not completed due to grade 4 urinary system adverse reactions.After neoadjuvant therapy,14 patients underwent abdominal perineal combined radical resection of rectal cancer(Miles),and 61 patients underwent anterior rectal cancer resection(Dixon).2.(1)among the 75 patients,there were 9 MSI cases and 66 MSS cases,and MSI was correlated with gender,which was common among women(p < 0.05).MSI was associated with pathological types,and was more common in mucinous adenocarcinoma(p < 0.05).MSI was independent of age,anal distance,clinical T and N stages before treatment(p > 0.05).(2)among the 75 patients,23 had EGFR gene mutation and 52 had no mutation.EGFR gene mutation was mostly found in mucinous adenocarcinoma(p < 0.05),which was independent of gender,age,distance from anus,T and N stage before treatment(p > 0.05).(3)there was no significant relationship between PIK3 CA and KRAS gene mutations and gender,age,distance from anus,pathological type and T and N stages before treatment(p > 0.05).3.(1)after neoadjuvant chemoradiotherapy,19 patients reached pCR,and the pCR rate was 25.33%(19/75).Univariate analysis showed that age,pathological type,T and N stage before treatment were all related to pCR after neoadjuvant concurrent chemoradiotherapy(p < 0.05),while gender and tumor distance from anus were not related to pCR(p > 0.05).(2)univariate analysis was performed on gene mutations associated with pCR,and the results showed that both MSI and PIK3 CA gene mutations were significantly correlated with pCR(p < 0.05).Patients with EGFR mutation had lower pCR than those without mutation(p < 0.05).KRAS gene mutation was not associated with pCR(p > 0.05).(3)logistic multivariate analysis showed that MSI and pre-treatment clinical T and N stages were independent influencing factors for pCR(p < 0.05).4.There was no correlation between MSI and PIK3 CA,EGFR and KRAS gene mutations(p > 0.05).Conclusion:1.MSI patients with rectal cancer are more common in women and mucinous adenocarcinoma,and EGFR gene mutation is more common in mucinous adenocarcinoma.PIK3 CA and KRAS gene mutations were independent of gender,age,tumor distance from anus,pathological type,pre-treatment clinical T and N stages.2.MSI,pre-treatment clinical T and N stages are independent factors affecting neoadjuvant chemoradiotherapy sensitivity,that is,early MSI and T stages and no lymph node metastasis may be important determinants of higher sensitivity,and MSI may be positively correlated with neoadjuvant radiotherapy sensitivity of rectal cancer.Gender,age,pathological type,PIK3 CA,EGFR and KRAS gene mutations were all independent of neoadjuvant sensitivity in colorectal cancer.3.MSI was independent of PIK3 CA,EGFR and KRAS gene mutations.