Study On The Correlation Between Expression Of Ubiquitin-specific Protease 3（USP3） And Clinical Pathological Features Of Colorectal Cancer

Background: Colorectal cancer（CRC）is one of the most common digestive tract malignant tumors in the world.The study of early familial cases has identified the main genes involved in CRC,such as protooncogenes KRAS,PIK3 CA and BRAF,and tumor suppressor genes APC and TP53.However,the incidence and mortality of colorectal cancer are still increasing year by year,and the onset age tends to be younger.Ubiquitin-specific protease 3（USP3）,as one of the important members of the family of ubiquitinated enzymes,can influence the signal transduction of target protein and regulate the occurrence and development of cancer.however,there is little research on the role of usp3 in the occurrence and development of colorectal cancer.Objective: To investigate the expression of USP3 in colorectal cancer tissues and their adjacent tissues and the relationship with clinical and pathological features of patients,to elaborate the significance of expression of USP3 in colorectal cancer tissues on prognosis of patients,and to analyze the mechanism of USP3 in the occurrence and development of colorectal cancer.Method: A total of 124 colorectal cancer tissues and 45 paired paracancerous tissue specimens were retrospectively analyzed.All the cases were followed up,and the pathological sections were re-read,and the clinical pathological data were organized.The tissue chips were made and the expressions of USP3 and P53 proteins were detected by immunohistochemistry（SP）.The fresh tissue samples of colorectal cancer and its adjacent tissues were collected and stored in liquid nitrogen,and the m RNA levels of USP3 in colorectal non-mucinous adenocarcinoma,mucinous adenocarcinoma and its adjacent tissues were detected by real-time quantitative PCR（RT-PCR）.The data were analyzed with IBM SPSS 25.0 statistical software.The correlation between the expression of USP3 in colorectal cancer and its adjacent cancers and clinical pathological characteristics parameters was analyzed with X2 test.The relationship between the expression of USP3 in colorectal cancer tissues and the clinicopathological parameters was established using binary Logistic regression.Kaplan-Meier survival curve was used for multivariate analysis of prognosis factors of colorectal cancer patients,and multivariate COX regression was used for survival analysis to exclude the interference of other confounding factors.P < 0.05 was considered to be statistically significant.Result:1.The positive expression rates of USP3 protein in colorectal cancer tissues and corresponding adjacent normal tissues are 38.71% and 57.78%,respectively;the positive expression rates in non-mucinous adenocarcinoma and mucinous adenocarcinoma subgroup of colorectal cancer patients are 28.16% and 90.48%,respectively;the positive expression rates in high-,medium-and low-differentiated groups are 16.67%,27.59% and 51.67%,respectively;The positive expression rates in the P53 mutant group and the wild-type group were 28.60% and 60.00%,respectively.There were significant differences in the correlation between the above clinical pathological features and the expression of USP3（P < 0.05）.The expression of USP3 protein in colorectal cancer was not correlated with the age,gender,tumor location,TNM stage,infiltration depth,lymph node metastasis,distant metastasis,KRAS and BRAF gene mutation.2.RT-PCR assay showed that the expression level of USP3 m RNA was lower in the colorectal non-mucinous adenocarcinoma tissue than in its paracancerous tissue,and the expression level in the mucinous adenocarcinoma tissue was higher than in its paracancerous tissue（P < 0.05）.3.Univariate survival analysis showed that the expression of USP3 protein in colorectal cancer had no correlation with the recurrence-free survival and overall survival of the patients.However,patients with histological type of non-mucinous adenocarcinoma,TNM stage I or II,no distant metastasis,no lymph node metastasis and P53 wild-type had better prognosis.Regression survival analysis showed that colorectal cancer patients with negative USP3,mutant P53,histological type of mucinous adenocarcinoma,and distant metastasis and lymph node metastasis were prone to postoperative recurrence.Conclusion:1.USP3 expression had no correlation with age,sex,tumor site,TNM stage,depth of invasion,lymph node metastasis,distant metastasis,KRAS and BRAF gene mutation in colorectal cancer patients.Negative expression of USP3 was associated with recurrence free survival in non-mucinous colorectal adenocarcinoma patients,suggesting that non-mucinous colorectal adenocarcinoma patients with negative expression of USP3 were prone to postoperative recurrence.2.The expression of USP3 in colorectal cancer tissues was significantly lower than that in paracancerous tissues,while the expression of USP3 in mucinous adenocarcinoma tissues was higher than that in mucinous adenocarcinoma tissues,suggesting that USP3 may be one of the important factors influencing the pathogenesis of non-mucinous adenocarcinoma and mucinous adenocarcinoma in colorectal cancer.3.The expression of USP3 in colorectal cancer was negatively correlated with P53 mutation,suggesting that USP3 may play a role in the occurrence and development of colorectal mucinous adenocarcinoma by regulating the P53 pathway.