| Background Pancreatic cancer is a kind of disease with rapid development and hidden pathogenesis.Many patients have no symptoms in the early stage of the disease.When there are obvious symptoms,such as jaundice,chronic abdominal pain,anemia and other symptoms,they often enter the late stage.The tumor has a high degree of malignancy,a poor prognosis,a high rate of postoperative recurrence and mortality,and the late patients often lose the opportunity of surgery and can not completely remove the tumor.According to statistics,the number of deaths in the world is more than 200000 every year.According to the data of China Cancer Center,the number of male and female pancreatic cancer cases in 2015 were 52200 and 37900 respectively.The death toll was 45600 and 33800,respectively.The current treatment of the disease is mainly surgery,followed by chemotherapy.Although in theory,patients with pancreatic cancer can benefit from gemcitabine,the first-line chemotherapy drug for pancreatic cancer,which can prolong the overall survival and disease-free survival.However,there are significant differences in the actual chemotherapy effect of many pancreatic cancer patients,who can not benefit from gemcitabine.The difference of chemosensitivity is the main reason for the decrease of therapeutic effect and the failure to prolong the overall survival(OS)and disease free survival(DFS)of the patients.Gemcitabine is hydrophilic and mainly depends on human equilibrium nucleoside transporter 1(h ENT1)to enter the cytoplasm,but not through the cell membrane by passive diffusion.In the absence of h ENT1,gemcitabine may be difficult to enter into tumor cells.Therefore,some scholars think that the expression of h ENT1 in pancreatic cancer may be related to the chemosensitivity of gemcitabine,and some researches have been carried out.However,up to now,there is not a completely unified conclusion about the chemosensitivity of h ENT1 and gemcitabine.Because of the differences in the selection of patients with pancreatic cancer and the detection methods of h ENT1,sometimes the two conclusions are completely opposite.Because there are few related studies in China,and there is no relevant report on the specific areas such as Inner Mongolia Autonomous Region,such as the population,ethnic groups,living habits,etc.,it is of definite significance to carry out this research.Objective The purpose of this study is to investigate the relationship between the expression of h ENT-1 and gemcitabine resistance in pancreatic cancer,to understand the effect of h ENT1 expression on gemcitabine chemotherapy in pancreatic cancer,and to verify whether gemcitabine can bring good benefits to postoperative patients with pancreatic cancer,so as to prolong their OS and DFS.The possibility of using h ENT-1 as a biomarker to predict the effect of gemcitabine chemotherapy after pancreatic cancer surgery was analyzed.Whether the general data and clinical data affect the expression of h ENT-1 in pancreatic cancer was analyzed.Methods Select the patients who meet the inclusion criteria(see below for details),collect their general data(gender,age,nationality,alcohol consumption,etc.)and clinical data(tumor location,tumor size,operation method,Pathological grade,TNM stage,pathological type,etc.),draw out the corresponding paraffin blocks of pancreatic cancer tissue to make sections,carry out the immunohistochemistry experiment of h ENT1 protein,and dye the intensity Finally,the expression of h ENT1 was determined by calculation.Follow up the prognosis of the corresponding slice patients,such as the overall survival,disease-free survival,reexamination results(CT,MRI and other imaging data).Finally,through statistical analysis of the expression of h ENT1 in pancreatic cancer tissue and the overall survival and disease-free survival of the patients,and to explore the independent influencing factors of the prognosis of gemcitabine chemotherapy.In addition,the general data and clinical data of the patients were compared qualitatively and quantitatively to determine whether they affected the expression of h ENT1 in pancreatic cancer.Results The median overall survival(OS)and disease free survival(DFS)were 20(95% CI,17.068-22.932)months vs 10(95% CI,8.390-11.610)months,15(95% CI,12.132-17.868)months vs 6(95% CI,4.944-7.056)months,respectively.The OS and DFS of patients in the high expression group were higher than those in the low expression group.The expression of hENT1 was correlated with OS and DFS in patients undergoing gemcitabine chemotherapy.The expression of h ENT1,pathological grade and lymph node metastasis were independent prognostic factors of OS.Moreover,the expression of h ENT1 and the pathological grade were independent prognostic factors of DFS.There was no significant difference in age,gender,nationality,long-term drinking,tumor location,operation mode,tumor diameter and pathological differentiation between pancreatic cancer patients and h ENT1(P > 0.05).Conclusion The expression level of h ENT1 in pancreatic cancer cells was related to the drug resistance of gemcitabine.The patients with high expression of h ENT1 had longer OS and DFS than those with low expression of gemcitabine,and the effect of gemcitabine chemotherapy was better.There was no correlation between the expression level of h ENT1 and the age,gender,long-term drinking,tumor location,operation mode,tumor diameter and pathological grade of pancreatic cancer patients.There was no significant difference between different ethnic groups.However,the grade of pathological differentiation and the expression level of h ENT1 in pancreatic cancer affect OS and DFS.It is a simple,convenient and reliable method to evaluate the expression of h ENT1 by immunohistochemistry.h ENT1 can be used as a biomarker to predict the effect of gemcitabine chemotherapy and provide support for patients to choose a better individualized chemotherapy scheme. |
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