A Comparative Study Of Chemotherapy Efficacy Between Colorectal Adenocarcinoma And Mucinous Adenocarcinoma Based On Organoid Drug Test

BackgroundColorectal cancer（CRC）is one of the most common malignant tumors in the world.Many colorectal cancer patients are diagnosed at an advanced stage.Chemotherapy is one of the main treatments for patients with colorectal cancer.Mucinous adenocarcinoma,a special histological type of colorectal cancer,characterizes with unique histologic,poor prognosis and shows response to chemotherapy.However,currently,there is no specialized chemotherapy regimen for CRC patients with mucinous adenocarcinoma.Preclinical model can perform chemotherapy drug screening in vitro and simulates the response to chemotherapy drugs.Tumor organoids,as a new type of preclinical model,compared with the current traditional tumor cell lines and animal models,were characterized by genetic stability,retention of tumor heterogeneity,low tissue demand,short culture cycle and high culture success rate.However,whether the tumor organoids can reflect the chemotherapy efficacy between patients with colorectal adenocarcinoma and mucinous adenocarcinoma still unknown.Therefore,this study constructed organoid from tumor and designed drug test to compare the efficacy of chemotherapy between colorectal adenocarcinoma and mucinous adenocarcinoma.ObjectivesCompare the efficacy of chemotherapy between colorectal adenocarcinoma and mucinous adenocarcinoma by culturing organoid and perform drug test.Methods1.Culture adenocarcinoma and mucinous adenocarcinoma organoids then perform organoid drug test.2.Compare the progression-free survival of patients with colorectal cancer adenocarcinoma and mucinous adenocarcinoma after adjuvant chemotherapy,and analyze the relationship between drug sensitivity results and progression-free survival.A total of 85 patients with colorectal cancer were enrolled and divided into adenocarcinoma group and mucinous adenocarcinoma group according to pathological results.The efficacy and progression-free survival of postoperative adjuvant chemotherapy in the two groups were analyzed.The tumor tissues of patients in the two groups were taken for organoid culture.Then we performed the drug test of tumor organoid.Finally,the relationship between drug test results and progression-free survival will be studied.Results1.According to the discharge criteria,85 patients were eventually included in this study,including 70 patients（82.35%）with adenocarcinoma and 15 patients（17.65%）with mucinous adenocarcinoma.Patients in both groups received FOLFOX/XELOX regimen after surgery.2.In organoid culture,there was no significant difference in the success rate of organoid culture between the adenocarcinoma group（AC）and mucinous adenocarcinoma group（MAC）（75.71%vs 73.33%,p=1.00）,the median cultured time was 7（4-12）days.In the drug sensitivity test of FOLFOX chemotherapy regimen,the IC50 value of organoid in the colorectal adenocarcinoma group（AC）was generally lower than that of the mucinous adenocarcinoma group（p<0.001）.3.The progression rate of postoperative adjuvant chemotherapy in MAC patients was significantly higher than that in AC patients（80%vs 38.57%,p=0.004）.The median progression-free survival between MAC and MAC patients was>23 months vs 6 months[95%CI（3.16,8.84）];the difference was statistically significant（log-rank p<0.001）.ConclusionOrganoid and drug sensitivity test can reflect the chemotherapy efficacy of colorectal adenocarcinoma and mucinous adenocarcinoma.In comparison of colorectal patients with mucinous adenocarcinoma and adenocarcinoma,mucinous adenocarcinoma patients showed poorer response to postoperative adjuvant chemotherapy,worse prognosis,and shorter progression-free survival.