Expression And Clinical Significance Of RNF6 In Colorectal Laterally Spreading Tumor

Objective:Colorectal cancer is a common malignant tumor of the digestive system,and the 2020 global cancer data report shows that the incidence of colorectal cancer ranks third in the world,and the mortality rate ranks second in the world,and the incidence and mortality rate are increasing year by year.Laterally spreading tumor(LST)is a precancerous lesion of colorectal cancer,which is a special type of adenoma larger than 1 cm in diameter and growing horizontally along the mucosal surface of the intestinal lumen.Benign LST lesions can progress to advanced colorectal cancer within 3 years,with an incidence of 8.4-52.5%.Studies have reported that Ring finger protein 6(RNF6)is overexpressed in colorectal cancer,promoting the invasion and migration of colorectal cancer cells,but the expression of RNF6 in laterally spreading tumors has not been reported.This study aims to analyze the expression of RNF6 in LST and explore whether RNF6 plays an important role in the transformation of LST into colorectal cancer.Methods:A total of 34 cases of colorectal laterally spreading tumors(LST group),41 cases of protruded-type colorectal adenomas(PA group),35 cases of colorectal cancer(CRC group)and 35 cases of adjacent normal mucosal tissues(NM group)who underwent colonoscopy or endoscopic treatment at the Digestive Endoscopy Center of the Affiliated Hospital of Chengde Medical College from August 2021 to September 2022 were collected.Real-time quantitative Polymerase Chain Reaction(RT-qPCR)and immunohistochemical staining(IHC)were used to detect the expression of RNF6 in tissues.Results:1.The immunohistochemical results showed that the positive expression rates of RNF6 protein in adjacent normal mucosal tissues,protruded-type adenomas,laterally spreading tumor,and colorectal cancer were 40%(14/35),46.3%(19/41),76.5%(26/34)and 91.4%(32/35).Among them,the positive expression rate and expression intensity of RNF6 protein in laterally spreading tumors were significantly higher than those of protruded-type adenomas and adjacent normal mucosal tissues(P<0.0083),and there was no significant difference between the positive rate and colorectal cancer(P>0.0083),and the positive intensity was lower than that of colorectal cancer(P<0.0083).2.The results of RT-qPCR showed that the expression of RNF6 mRNA in laterally spreading tumors was higher than that of adjacent normal mucosa(adjusted P<0.05),lower than that of colorectal cancer(adjusted P<0.05),and there was no significant difference with raised adenomas(adjusted P>0.05).3.The expression of RNF6 protein and mRNA in laterally spreading tumors was compared with the clinicopathological characteristics of patients,showing that the expression of RNF6 protein and mRNA was independent of the patient’s age,gender,BMI,tumor diameter,tumor location,pathological type,and LST subtype,and was related to the intraepithelial neoplasia grade of the tumor(P<0.05).Further analysis found that there was a statistically significant difference in the positive expression intensity of RNF6 between different intraepithelial neoplasia grades of LST(P<0.05).Conclusions:1.The expression levels of RNF6 mRNA and protein in laterally spreading tumors were higher than those in protruded-type adenomas and adjacent normal mucosal tissues,and lower than those in colorectal cancer.2.In laterally spreading tumors,the expression of RNF6 protein in high-grade intraepithelial neoplasia was higher than that in low-grade intraepithelial neoplasia,suggesting that RNF6 may be related to malignant transformation of laterally spreading tumor.