Exploring The Value And Mechanism Of LncRNA-UFC1 In Early Diagnosis,Prognosis And Radiation Resistance Of Pancreatic Cancer

Objective:Early detection and diagnosis are of great significance to the survival and prognosis of patients with pancreatic cancer.LncRNA-UFC1(UFC1)is a new type of RNA molecule,but its expression and value in pancreatic cancer is not clear.Based on the availability of peripheral blood,this study intends to detect the expression of UFC1 in peripheral blood to early diagnose pancreatic cancer and predict the prognosis.Methods:The serum samples of 48 patients with pancreatic cancer diagnosed in our hospital from January 2012 to December 2014 were collected.All patients had not received any form of antineoplastic therapy.At the same time,the serum of 40 age-matched healthy volunteers who underwent physical examination in the health examination center of our hospital from February 2014 to December 2014 were collected as the control group.QRT-PCR was used to detect the level of UFC1 expression in serum of patients with pancreatic cancer and healthy volunteers.All statistical data were analyzed with SPSS 19.0 software.The correlation between the expression level of UFC1 in serum and clinicopathological features was analyzed by chi-square test or Fisher exact probability method.The survival curve was drawn by Kaplan-Meier method,and the difference was tested by Log-Rank test.The threshold of serum UFC1 was statistically analyzed by the receiver working characteristic curve(ROC curve).Univariate and multivariate Cox regression analysis were used to evaluate the prognosis.Results:The expression level of UFC1 in serum of patients with pancreatic cancer was significantly higher than that of healthy volunteers.According to the statistical analysis of ROC curve,the serum UFC1 threshold can be used to distinguish between patients and healthy people,and the AUC value is 0.810(95%CI:0.719～0.900,P<0.001).The expression of UFC1 in serum of patients with pancreatic cancer was correlated with clinical stage,regional lymph node metastasis and distant metastasis.Kaplan-Meier survival analysis showed that the disease-free survival time(DFS)and overall survival time(OS)of the patients with high expression of UFC1 in serum were shorter than those in the low expression group.Multivariate analysis showed that clinical stage and serum UFC1 expression level were the main independent prognostic factors in patients with pancreatic cancer.Conclusion:The expression level of serum UFC1 has potential guiding significance in diagnosis and prognosis prediction of pancreatic cancer.Objective:Benefitting from the development of molecular biology,the important role of lncRNA in various biological processes has been discovered.Among them,UFC1 is a new type of RNA molecule discovered in recent years.Our previous study found that there was a difference in the expression of UFC1 between pancreatic cancer and healthy controls.The purpose of this study was to further clarify the difference of UFC1 expression in pancreatic cancer tissues and normal tissues,cancer cell lines and normal pancreatic epithelial cells.Methods:The fresh surgical specimens of 23 patients with pancreatic cancer in Zhejiang Cancer Hospital from January 2018 to December 2019 were collected.All the patients had not received antineoplastic therapy before operation.Real-time fluorescence quantitative PCR was used to detect the expression of UFC1 in pancreatic cancer tumor specimens,paracancerous normal tissues,pancreatic cancer cell lines PANC1,PaTu8988,BxPC3 and SW1990 and pancreatic normal epithelial cell line HPDE.All the experimental data were statistically processed with SPSS 19.0 software.The mean values of the two samples were compared by t-test of two independent samples,and the samples were compared by the analysis of variance of completely random design data(Levene test was used to test the homogeneity of one-way variance).P<0.05 was considered to be statistically significant.Results:The expression of UFC1 was detected in 23 cases of pancreatic cancer and normal tissues around the cancer.The expression of UFC1 in pancreatic cancer tissues was significantly higher than that in normal tissues around cancer,and the expression level of UFC1 in many pancreatic cancer cell lines was significantly higher than that in normal pancreatic epithelial cells.Conclusion:The results further suggest that UFC1 may play an important role in the occurrence and development of pancreatic cancer,which is worthy of further exploration.Objective:Radiotherapy is an important treatment for advanced pancreatic cancer.We intend to explore the role and molecular mechanism of UFC1 in radiation-induced autophagy and radiation resistance of pancreatic cancer cells by silencing the expression of UFC1 in pancreatic cancer cell lines and receiving X-ray ionizing radiation of 6 Gy.Methods:Pancreatic cancer cell lines were transfected with UFC1 siRNA or blank control by liposome transfection.The transfection efficiency was detected by qRT-PCR.Western Blot was used to detect the expression of autophagy-related proteins LC3 and p62 before and after radiation.Clone formation assay was used to detect the changes of radiosensitivity of cells before and after UFC1 knockout.The luciferase activity of the samples was detected by double luciferase reporter gene detection system.The changes of radiosensitivity of cells were detected after co-transfection of siUFC1 and miR-498 inhibitor.The experimental data were expressed by mean ±standard deviation and statistically processed by SPSS 19.0 software.The mean values of the two samples were compared by t-test of two independent samples(independent sample T-test),and the mean values of more than two groups of samples were compared by the analysis of variance of completely random design data(Levene test was used to test the homogeneity of one-way variance).P<0.05 was considered to be statistically significant.Results:When UFC1 was knocked out in pancreatic cancer cells and ionized by 6 Gy X-rays,the autophagy induced by radiation was significantly decreased,while the radiosensitivity of cells was significantly increased.Knockout of miR-498 can reverse the radiosensitization induced by knockout of UFC1.Conclusion:UFC1 may be involved in the radiation-induced autophagy of pancreatic cancer cells and is related to the radiosensitivity of pancreatic cancer cells.MiR-498 can specifically inhibit the expression of UFC1 and regulate the radiosensitivity of pancreatic cancer cells.