| As a highly aggressive malignant disease,the prognosis of patients with pancreatic ductal adenocarcinoma(PDAC)is poor.The incidence of PDAC has increased year by year.Surgical resection is potentially the only choice for curative treatment of pancreatic cancer.However,due to lack of specific clinical manifestations,most of the patients are not suitable for curative operation,with a 5-year survival rate of less than 5%.CA19-9 and CEA are the most used biomarkers in the diagnosis of pancreatic cancer.However,the sensitivity and specificity of CA19-9 and CEA as a marker for pancreatic cancer screening were obviously insufficient.Therefore,it is of great clinical value to find new biomarkers for the early diagnosis and treatment of pancreatic cancer.microRNAs(miRNA)have been shown to influence cell differentiation,proliferation,and apoptosis.They represent only 3%of the human genome,but regulate 20%-30%of the protein coding genes.Differential expression of miRNA was found in a variety of tumor tissues,including pancreatic cancer,suggesting that miRNA could be a potential tumor marker.In this study,we used The Cancer Genome Atlas/TCGA database to screen differentially expressed miRNAs with prognostic value in pancreatic cancer,for further evaluate in Chinese population.The information of miRNA expression in 178 cases of pancreatic carcinoma in situ and 4 cases of normal pancreatic tissue in the TCGA database were analyzed.49 differentially expressed miRNA were identified.Considering the role on the prognosis of PDAC,miR-628-3p and miR-3613-5p were selected for the further study.In this study,the clinical pathological data and tissue samples of 98 pancreatic cancer patients who underwent radical resection were collected.Differential expression of miR-628-3p and miR-3613-5p were found in those pancreatic cancer tissue and adjacent normal tissues(p<0.05).The expression of miR-628-3p was significantly correlated with lymph node metastasis(p=0.041)and preoperative serum CA19-9 level(p=0.005).And miR-3613-5p was correlated with recurrence and metastasis of PDAC after radical resection(p=0.046).There is no relationship between those two kinds of miRNA with sex,age,tumor size,tumor location,tumor differentiation degree,the presence of tumor thrombus,the presence of neural invasion and the level of serum CEA of PDAC patients.Survival analysis showed that the expression level of miR-3613-5p in pancreatic cancer affected the disease-free survival and overall survival,but the expression of miR-628-3p was not related to the prognosis of patients with pancreatic cancer.In patients with low expression of miR-3613-5p had a decreased disease free survival time(p=0.011)and even worse prognosis(p=0.028).Functional experiments showed that both miR-628-3p and miR-3613-5p inhibited the growth and proliferation of pancreatic cancer cells.In addition,miR-628-3p could inhibit the migration of pancreatic cancer cells.MiR-3613-5p can affect the cell cycle and apoptosis of pancreatic cancer cells,and decrease the number of G2 cells and increase the apoptosis.In summary,by analyzing TCGA pancreatic cancer miRNA database,we found miR-628-3p and miR-3613-5p was differential expressed in pancreatic cancer.Further studies showed that the expression of miR-628-3p related with the lymph node metastasis and serum CA19-9 level in PDAC patients.Functional experiments demonstrated that miR-628-3p could affect the proliferation and migration of pancreatic cancer cells,suggesting that it might be involved in pancreatic cancer invasion and metastasis.MiR-3613-5p is associated with recurrence and metastasis of pancreatic cancer,and affects both the disease free survival and the overall survival.Functional experiments showed that miR-3613-5p could inhibit the cell growth and proliferation and promote the apoptosis of pancreatic cancer cells.It might be a new diagnostic and prognostic marker for pancreatic cancer.Background:The median age of patients with pancreatic ductal adenocarcinoma(PDAC)is approximately 70 years,and it rarely affects individuals younger than 45 years,when it is defined as early-onset pancreatic cancer(EOPC).Little is known about risk factors and outcomes for EOPC patients.Aim:To evaluate the clinico-pathological features,risk factors,and outcomes of EOPC.Methods:A retrospective analysis of pancreatic cancer patients diagnosed between January 1999 and December 2014 was performed.Information about environmental risk factors,clinical characteristics,treatment,and survival was collected.The risk factors of EOPC patients were compared to normal-onset pancreatic cancer(NOPC)patients.Results:Of 1789 patients with pathologically proven PD AC,156(8.7%)had EOPC.There was no difference regarding alcohol use,BMI,weight loss,and tumor location between EOPC and older subjects.EOPC patients were more likely to be male(75 vs 63.9%)and to have a history of tobacco use(34.6%vs 25.9%),compared NOPC patients.Among the 156 EOPC patients,there were 117(75%)males,and 39(25%)females,from 17 to 45 years old.Fifty-four(34.6%)had a smoking history,55 had used alcohol,and 27(17.3%)had a family history of cancer.For treatment,32 underwent surgery to attempt curative resection of localized disease and 74 had palliative surgery.The median overall survival for the 156 EOPC patients was 8 ± 0.5 months,with 1.2 year survival rates of 25.4 and 8%,respectively.For EOPC patients,the median overall survival of the patients treated with radical resection,palliative surgery,and medical treatment was 19 ±2.5,8 ± 0.6 and 6 ± 0.3 months,respectively.The 1-year survival rates were 77.5,17.6 and 4%,respectively.Survival analysis showed that the tumor size,tumor location,differentiation,treatment procedure,TNM stage,and first symptoms were associated with the overall survival(p<0.05).Cox regression revealed that the TNM stage(RR=3.427;95%CI:1.802-6.519)and tumor size(RR=1.911;95%CI:1.054-3.463)are independent prognostic factors for EOPC patients.Conclusion:EOPC was associated with male gender and smoking history.Although EOPC patients display aggressive disease and have a worse outcome,radical resection is the best treatment.The TNM stage and tumor size are independent prognostic factors. |
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