The Role Of Plasma MicroRNA In The Diagnosis Of Cholangiocarcinoma

Cholangiocarcinoma( CCA) were malignant hepatobiliary cancers with features of cholangiocyte differentiation. Early CCA was typically small and asymptomatic, and the high mortality from CCA was mainly due to late presentation. When diagnosed in end-stage CCA were 6.78 times more likely to die than in the early stage. Therefore, early diagnosis and treatment of CCA is an important way to reduce death rate from CCA. Carbohydrate antigen 19-9( CA19-9), as common serum diagnostic indicators for diagnosis of CCA, have no sufficient sensitivity and specificity to facilitate the early detection. Therefore, study should be focus on the discovery of novel and reliable biomarkers for mass screening and early detection of CCA.Recently circulating microRNA( miRNA) became the research focus, which could be stably present in the circulating blood. Circulating miRNA was of great value with high accuracy, specificity and sensitivity in the diagnosis of malignant tumor. What’s more, there were different miRNA expression pattern in different types of tumors. These characteristics of circulating miRNA were better than the current circulating blood marker. An increasing number of evidences showed that circulating miRNA could be used in the diagnosis and analysis of tumor diseases. Compared with the organization miRNA, research of circulating miRNA was still relatively absence.The study aims to found differentially expressed miRNAs of 18 kinds of candidate plasma miRNAs in CCA and nomal controls( NC), and analysis their detecting accuracy. To further analyzed the relationship between the miRNA and clinical characteristics.Objectives: To found differentially expressed miRNAs of 18 kinds of candidate plasma miRNAs in CCA and NC, and analysis their detecting accuracy. To further analyze the relationship between the miRNA and clinical and pathological features.Methods:1 Fresh blood specimens, including 16 CCA and 14 NC, were obtained from the Second Hospital of Hebei Medical University. Separated plasma was used in this experiment.2 Reverse transcription-quantitative polymerase chain rection( RT-qPCR) was used to detect the differentially expressed of 18 kinds of candidate plasma miRNA in CCA and NC.3 Comparing the diagnostic accuracy between single miRNA and the 3-miRNA Panel used Receiver operating characteristic curve( ROC) curve.Results: 1 There was no significant difference in average age, gender between patients with CCA and NC; 2 The RT-qPCR result indicated that 5 of 18 plasma miRNA had an upward trend in CCA compared with NC, incluing miR-21-5p,-25-3p,-26a-5p,-374a-5p and miR-92a-3p. There were obvious differences in miR-92a-3p expression between CCA and NC( 0.1809±0.4347 vs. 0.0654±0.1165, P <0.05), no other significant difference( P > 0.05). Thirteen of eighteen plasma miRNA had an downward trend in CCA compared with NC, incluing miR-16-1-3p, let-7a-5p,-7b-5p,-7c-5p,-7f-5p, miR-494-3p,-124-3p,-150-5P,-320 a,-326,-373-3P,-204-5p and miR-186-5p. There were obvious differences in miR-204-5p( 0.0028±0.0108 vs. 0.0102±0.0246, P <0.05) and miR-186-5p( 0.0026±0.0086 vs. 0.0066±0.0072, P <0.05) expression between CCA and NC, no other significant difference( P > 0.05); 3 MiR-204-5p expression levels were significantly lower in patients with lymphatic metastasis than in those without( P < 0.05), have no correlate with other clinical characteristics. The expression of miR-92a-3p and miR-186-5p have no significant relationship with clinical characteristics; 4 Not differentially expressed miRNAs, let-7b-5p expression levels were significantly lower in patients with lymphatic metastas is than in those without( P < 0.05), miR-494-3p significantly associated with TNM stage, the higher the stage, the lower the expression( 0.0600±0.0832 vs. 0.0095±0.0021, P < 0.05), the expression of miR-373-3p was significantly l- ower when the differentiation was lower( 0.0017±0.0179 vs. 0.0003±0.0006,P < 0.05). 5 The AUC range of singel miRNA which differentially expressed is 0.708 ~ 0.750, 95CI% range is 0.524 to 0.924, the 3-miRNA Panel of 3 miRNA joint model diagnostic accuracy of(AUC, 0.879; 95CI%, 0.749 ~ 1.010; P < 0.001).Conclusions:1 MiR-204-5p,-92a-3p and miR-186-5p could be used for early diagnosis of CCA. Three-miRNA Panel could increase the accuracy, sensitivity and specificity of diagnosis.2 MiR-204-5P could be used as a plasm biomarker for the assessment of lymphatic metastasis of CCA.