Serum MiR-486-5p Combined With CA19-9 In The Diagnosis Of Early Pancreatic Cancer

BackgroundPancreatic cancer has hidden early symptoms and a high degree of malignancy.Most patients have been diagnosed at an advanced stage and lose the best opportunity for surgery,resulting in a poor prognosis.The lack of early detection of biomarkers is an urgent problem to be tackled in the diagnosis and treatment of pancreatic cancer.However,serum carbohydrate antigen19-9（CA19-9）is currently the only recognized circulating biomarker for pancreatic cancer,not sensitive and specific for early diagnosis,and it has limitations for diagnosis.Recently,people are exploring the potential of DNA,mRNA and non-coding RNA（ncRNA）as biomarkers in different diseases and cancers.Among all ncRNAs,microRNAs（miRNAs）have been studied most deeply.Although the exact mechanism by which these miRNAs affect cancer is not fully understood,miRNAs are often found to be dysregulated in different types of cancer,leading to excessive cell proliferation,apoptosis inhibition,and abnormal migration.In addition,because miRNAs are highly stable in the blood circulation and are not easily degraded,compared with other inspection methods,blood testing is simpler,reproducible,and low-risk.And some circulating miRNAs come from tumor tissues,which can serve as a stable circulating biomarker for tumors.Previous studies have proved that miR-486/miR-486-5p is dysregulated in pancreatic cancer tissues and promotes the occurrence and development of pancreatic cancer.However,there lack studies on serum miR-486-5p as biomarker for pancreatic cancer,and overlapping studies are also insufficient.ObjectiveTo investigate the expression level of serum miR-486-5p and significance of the diagnosis in pancreatic cancer,and explore the value of combined CA19-9 in the diagnosis of early pancreatic cancer.MethodsAll subjects（105 cases）were selected from Qingdao Municipal Hospital from December 2018 to December 2020,40 cases of pancreatic cancer group（including 11cases of early pancreatic cancer and 29 cases of advanced pancreatic cancer）,21 cases of acute or chronic pancreatitis and 44 cases of healthy control group.Real-time quantitative reverse-transcription PCR（q RT-PCR）was used to determine the expression level of serum miR-486-5p in all subjects.The relative quantity was calculated according to 2^-△△Ct and used for data analysis.Enzyme-linked immunosorbent assay（ELISA）was used to detect the expression level of CA19-9.Clinical data including age,sex,tumor size,location,lymphatic metastasis and distant metastasis were collected.Analysis of differences in serum miR-486-5p expression levels under different clinical features of pancreatic cancer.And construct receiver operating characteristic curve（ROC curve）,compare area under the curve（AUC）,specificity and sensitivity,and evaluate the diagnostic value of miR-486-5p and combined CA19-9 for early pancreatic cancer.Using SPSS 25.0 and Graph Pad Prism 8.0 software to analyze all data and draw chart.P<0.05 is considered to have statistical difference.Result（1）The relative expression of miR-486-5p in pancreatic cancer,early pancreatic cancer and middle and advanced pancreatic cancer was 3.19（2.01,5.08）,2.01（1.23,2.22）and 3.82（2.26,6.36）respectively,which were significantly higher than that in acute and chronic pancreatitis group 1.00（0.32,1.43）and healthy control group 0.99（0.24,1.01）（all P<0.001）.（2）With the later TNM stage of the tumor,the expression level of miR-486-5p is higher,and it is related to lymphatic metastasis and distant metastasis（P<0.05）.In addition,there is no significant difference with gender,age,tumor location and tumor size.（3）Mi R-486-5p and CA19-9 independently differentiated pancreatic cancer group and acute and chronic pancreatitis group（AUC 0.86 and 0.84,respectively;sensitivity77.5%and 80%,respectively;specificity 85.7%and 66.7%,respectively）;distinguish between pancreatic cancer pancreatic cancer group and healthy control group（AUC0.90,0.89,respectively;sensitivity 90.0%,80%,respectively;specificity 81.8%,75%,respectively）.distinguish the early pancreatic cancer group from the acute and chronic pancreatitis group（AUC 0.73,0.71,respectively;sensitivity 63.6%,63.6%,specificity,81%,66.0%,respectively）and distinguish the early pancreatic cancer group from the healthy control group（AUC is 0.80,0.78;sensitivity is 81.8%,63.6%;specificity is84.1%,75.0%）AUC is similar.Combine miR-486-5p with CA19-9 to distinguish pancreatic cancer group from acute and chronic pancreatitis group（AUC 0.92;sensitivity 87.5%;specificity 85.7%）,distinguish pancreatic cancer group from healthy control group（AUC 0.94;Sensitivity 95.0%;specificity 86.4%）,distinction between early pancreatic cancer group from acute and chronic pancreatitis group（AUC 0.76;sensitivity 81.8%;specificity 76.2%）and distinction between early pancreatic cancer group from healthy control group（AUC is 0.82;sensitivity 81.8%;specificity 88.6%）.The AUC,sensitivity and specificity of combining two indicators in the diagnosis of pancreatic cancer are better than those of CA19-9 alone.Conclusion（1）The expression of serum miR-486-5p is up-regulated in pancreatic cancer,which can be used as a potential serological biomarker for pancreatic cancer.（2）The expression of serum miR-486-5p was correlated with TNM stage,lymphatic metastasis and distant metastasis,and was independent of gender,age,tumor location and tumor size.（3）The diagnostic value of miR-486-5p combined with CA19-9 in early pancreatic cancer is better than that of CA19-9 alone.