The Correlation Between The Therapeutic Effect Of Neoadjuvant Radiotherapy And Chemotherapy And The Expression Level Of Aim2 In Rectal Cancer

Objective: Rectal cancer is a malignant tumor with a high incidence rate in China and even the world.Its incidence rate has increased year by year,which has seriously affected the health of the people,and has also increased the burden on society.The treatment of rectal cancer is a combination of surgery,radiotherapy and chemotherapy.Neoadjuvant radiotherapy and chemotherapy can be used in patients with local advanced stage(T3 or above)or clinical stage II or III before operation.However,a large number of clinical practice found that not all patients with rectal cancer are sensitive to neoadjuvant radiotherapy and chemotherapy,and there are significant differences in tumor regression,while some patients have serious adverse reactions of radiotherapy and chemotherapy.In addition,during neoadjuvant radiotherapy and chemotherapy,some patients developed tumor progression,or distant metastasis,or even lost the opportunity of surgery.In order to reduce the burden of patients and achieve individualized and precise treatment,it is necessary to find indicators that can predict the efficacy of neoadjuvant radiotherapy and chemotherapy in patients with rectal cancer.As a pattern recognition receptor(PRR),melanoma deficiency factor 2(AIM 2)is recognized by human beings.Aim2 can activate the pathway of inflammatory corpuscles and produce inflammatory effects to resist the invasion of microorganisms by recognizing pathogen related molecular patterns(PAMP)such as viruses,bacteria,fungi and even their own double stranded DNA.Recently,it has been found that in the process of DNA damage caused by radiotherapy and chemotherapy,the aim2 protein in the nucleus combines with the damaged double stranded DNA,which can synthesize the inflammatory complex,activate caspase-1 and mediate the apoptosis induced by IL-1 β.After the rectal cancer cells are treated with radiotherapy and chemotherapy,the aggregation of aim2 in the cell nucleus can be found.Therefore,it is speculated that the expression of aim2 plays a role in the process of radiotherapy and chemotherapy of rectal cancer.Methods: The rectal cancer patients who completed neoadjuvant radiotherapy and chemotherapy and received surgery between 2016 and 2019 were included in our hospital.The postoperative specimen pathology was divided into two groups according to the tumor regression: group A(better regression)and group B(worse regression).The TRG scores of pathological specimens in group A were 0,1,and those in group B were 2,3.The clinicopathological data of the two groups were collected,including sex,age,distance from the lower edge of the tumor to the anal edge before radiotherapy and chemotherapy,tumor size,tumor markers(CEA,CA19-9)before radiotherapy and chemotherapy,whether there was distant metastasis,c TNM stage,radiotherapy and chemotherapy plan,time from the end of radiotherapy and chemotherapy to operation,CEA and CA19-9 after radiotherapy and chemotherapy.At the same time,the expression of aim2 in the tumor tissue was obtained by immunohistochemical staining.The expression level of aim2 in tumor tissue before radiotherapy and chemotherapy was compared between the two groups.The relationship between the expression of aim2 and the degree of tumor regression was compared.SPSS22.0 was used to analyze the data.By using t-test,variance analysis or fish e r accurate probability analysis.Because the specimens with a TRG score of 0 or1 showed complete tumor regression or only a few tumor cells existed,and there was a lot of information loss in the specimens after operation,so the TRG score of 2 was set as group C,and the TRG score of 3 was set as Group D.the expression of tissue grade,p53,VEGF(vascular endothelial growth factor),Ki-67,CD34 were compared between the two groups.P < 0.05 was regarded as statistically significant.Results: 206 cases of colorectal cancer who completed neoadjuvant radiotherapy and chemotherapy were selected from the database.51 cases gave up or did not complete the tumor resection because of economy,complications of radiotherapy and chemotherapy,other organ diseases,distant metastasis and other reasons.The other 155 patients completed neoadjuvant radiotherapy,chemotherapy and surgery according to the guidelines.The postoperative pathological report showed that 33 patients(21%)achieved complete remission(trg0 score),28 patients(18.0%),68 patients(43.9%)and 26 patients(16.8%)with TRG1,2 and 3 scores,respectively.Statistical analysis showed that there was no significant difference in gender,age,distance from the lower edge of tumor to the anal edge,tumor size,CEA,CA19-9 and clinical stage between the two groups(P > 0.05).There was no significant difference between the two groups in radiotherapy and chemotherapy plan,radiotherapy and chemotherapy(preoperative CEA,CA19-9),radiotherapy to operation time(P<0.05).There was no significant difference in histological grade,expression of p53,Ki-67 and CD34 in C(trg2)and D(trg3)groups(P > 0.05),among which 40 cases(58.8%)were VEGF positive in C group and 21 cases(81.8%)were VEGF positive in D group(P = 0.046 < 0.05).The expression of aim2 was detected in 87 cases before radiotherapy and chemotherapy,28 cases in group A(TRG score 0,1)and 59 cases in group B(TRG score 2,3).Chi square test showed that the proportion of high expression of aim2 in tumor tissue before radiotherapy and chemotherapy was higher(35.7% vs 11.9%),the difference was statistically significant(P = 0.009).In 58 patients,the expression of aim2 was obtained before radiotherapy and chemotherapy and after operation.There was no significant difference in the expression of aim2 between the two groups(P = 0.719 > 0.05).Conclusion: there is no correlation between the therapeutic effect of neoadjuvant radiotherapy and chemotherapy,such as age,sex,tumor location,tumor size,c TNM stage,CEA and CA19-9,radiotherapy and chemotherapy plan,waiting time from the end of radiotherapy to the operation,etc.In patients with better tumor regression,the proportion of high expression of aim2 in tumor tissue was higher before radiotherapy and chemotherapy.That is to say,patients with high expression of aim2 in tumor tissue before radiotherapy and chemotherapy are more likely to obtain better tumor regression degree.The correlation between the expression of aim2 and the degree of tumor regression has not been confirmed.In conclusion,the study of predictors of neoadjuvant radiotherapy and chemotherapy response for rectal cancer will be a hot topic in the future,and we expect more evidence.