Correlation Between P70S6K1 Protein Expression And Prognosis Of Gemcitabine Chemotherapy In Patients With Pancreatic Cancer

Background: Pancreatic cancer(PC)is a deadly digestive system malignant tumor,the prognosis of patients are often poor,radical surgical resection of the primary lesions is the high cure potential treatment,but a large number of patients often found is late,not to surgery,and surgical treatment after local and distant recurrence rate is higher,so early resection combined with postoperative adjuvant chemical therapy is considered an important treatment of pancreatic cancer.Postoperative application of gemcitabine chemotherapy can theoretically delay the time of tumor recurrence,but clinical statistics show that some patients,even with previous surgery combined with postoperative gemcitabine adjuvant chemotherapy,still do not achieve good efficacy and often have poor prognosis.The p70 ribosomal protein S6 kinase 1(p70 ribosomal protein S6 kinase 1,p70S6K1)is a serine /threonine kinase,As a phosphatidylinositol 3-kinase(phosphatidylinositol 3-kinase,PI3K)/ Protein kinase B(protein kinase B,AKT)/ target of rapamycin(mammalian target of rapamycin,Important substrates of the m TOR)pathway,Ability to regulate the cell cycle,cell apoptosis,cell growth,and autophagy;This protein can induce oxygen deficiency,Regulation ate tumor vessel formation,There are in vitro experiments that link p70S6K1 protein to the efficacy of gemcitabine chemotherapy,Some researchers believe that the overexpression of p70S6K1 protein can be used as a prognostic marker for breast cancer,colorectal cancer,lung cancer and other tumors;No unified conclusion on the role of p70S6K1 protein in pancreatic cancer.Objective: By studying the protein expression of p70S6K1 in pancreatic cancer,exploring the correlation between p70S6K1 expression and the prognosis of gemcitabine chemotherapy treatment in pancreatic cancer,analyzing the relationship between p70S6K1 expression and the pathological characteristics of patients treated with gemcitabine chemotherapy in pancreatic cancer,and exploring whether p70S6K1 protein can be used as a potential biomarker to predict the effect of chemotherapy treatment in pancreatic patients.Method: Collect the general data and clinical data of patients undergoing pancreaticoduodenal surgery from January 2015 to December 2020,Selected the 58 pancreatic cancer patients who met the inclusion criteria,Wax block samples of their pancreatic tumor tissue were selected,Sections were prepared for the immunohistochemical experiments,Based on the staining intensity of p70S6K1 protein in pancreatic cancer cell tissues and the proportion of positive cell staining,The p70S6K1 protein expression level was calculated after scoring,Group the different p70S6K1 protein expressions,The overall survival,disease-free survival,Analyzing the relationship between p70S6K1 protein expression and overall survival and disease-free survival of postoperative gemcitabine chemotherapy in patients with pancreatic cancer,Explore the independent factors affecting the prognosis;Statistical analysis of the expression level of p70S6K1 protein with general and clinical data of pancreatic cancer patients.Results: Median overall survival in the high p70S6K1 protein expression group versus the low p70S6K1 protein expression group(Overall Survival,OS)were 9(95%CI 6.714-11.286)months vs 19(95% CI 16.608-21.392)months,respectively;Disease-free survival in the high p70S6K1 protein expression group and the low p70S6K1 protein expression group(Disease Free Survival,DFS)were 6(95%CI 3.750-8.250)months vs 15(95% CI 13.106-16.894)months,respectively.Both OS and DFS in the high p70S6K1 protein expression group were lower than those in the low p70S6K1 protein expression group.The level of p70S6K1 protein expression correlated with OS of gemcitabine chemotherapy in pancreatic cancer patients.The expression level of p70S6K1 protein,the degree of pathological differentiation and lymph node metastasis were independent prognostic factors affecting OS and DFS.There was no significant difference between p70S6K1 protein expression and sex,age,long-term alcohol history,tumor diameter and tumor T stage(P>0.05),and no significant difference between p70S6K1 protein expression and the degree of pathological differentiation and presence of lymph node metastasis(P <0.05).Conclusion:Compared with patients with high expression of p70S6K1 protein,OS and DFS of gemcitabine chemotherapy were shorter than those with low expression of p70S6K1 protein.High expression of p70S6K1 protein in multivariate analysis was one of the independent prognostic factors affecting shorter OS and DFS of gemcitabine chemotherapy after pancreatic cancer.The expression level of p70S6K1 protein is associated with the degree of pathological differentiation and lymph node metastasis of pancreatic cancer patients,and there is no correlation with tumor diameter,T stage,age,long-term alcohol drinking history,gender and ethnicity of pancreatic cancer patients.Whether p70S6K1 protein can be a target to predict the effect of gemcitabine chemotherapy in pancreatic cancer patients needs to be studied in larger clinical cases.