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MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

Voigtländer T, Gupta SK, Thum S, Fendrich J, Manns MP, Lankisch TO, Thum T - PLoS ONE (2015)

Bottom Line: All validated miRNAs were significantly lower in healthy individuals.MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile.Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center-Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.

ABSTRACT

Background and aim: Patients with primary sclerosing cholangitis (PSC) are at high risk for the development of cholangiocarcinoma (CC). Analysis of micro ribonucleic acid (MiRNA) patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.

Methods: Serum and bile from consecutive patients with PSC (n = 40 (serum), n = 52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12). The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.

Results: Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile.

Conclusions: Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

No MeSH data available.


Related in: MedlinePlus

ROC curves for serum miRNAs.Receiver operating characteristics (ROC) curves for the detected serum MIRNAs. MiR-1281 and miR-126 showed the highest area under the curve (AUC) value in ROC curve analysis.
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pone.0139305.g003: ROC curves for serum miRNAs.Receiver operating characteristics (ROC) curves for the detected serum MIRNAs. MiR-1281 and miR-126 showed the highest area under the curve (AUC) value in ROC curve analysis.

Mentions: Validation was then performed in 83 serum samples for the aforementioned miRNAs. C. elegans miR-39 values were similar in both groups (PSC and CC) (S1 Fig). Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC (Figs 1 and 2 (miR-1281, miR-126) and S2–S4 Figs (miR-26a, miR-30b, miR-122)). MiR-1281, miR-126, and miR-26a displayed higher levels in patients with PSC. In addition, miR-30b and miR-122 were also upregulated in patients with PSC, while miR-194 showed no significant difference. All the validated serum miRNAs were significantly higher in the study patients compared to healthy individuals. In order to compare the diagnostic potential of the different miRNAs a ROC curve analysis was performed. The area under the curve (AUC) values for the different miRNAs were as follows; MiR-1281 0.83 (95% confidence interval (CI) 0.72–0.91, p = 0.001), miR-126 0.87 (95% CI 0.77–0.94, p = 0.001), miR-26a 0.78 (95% CI 0.66–0.87, p = 0.001), miR-30b 0.78 (95% CI 0.67–0.87, p = 0.001) and miR-122 0.65 (95% CI 0.53–0.76, p = 0.032), respectively (Fig 3). The sensitivity and specificity values to distinguish between patients with PSC and CC are given in Table 1. A combination of the different miRNAs in a logistic regression model did not significantly improve the diagnostic accuracy (data not shown). Correlation analysis showed no correlation between the miRNAs and cholestatic parameters.


MicroRNAs in Serum and Bile of Patients with Primary Sclerosing Cholangitis and/or Cholangiocarcinoma.

Voigtländer T, Gupta SK, Thum S, Fendrich J, Manns MP, Lankisch TO, Thum T - PLoS ONE (2015)

ROC curves for serum miRNAs.Receiver operating characteristics (ROC) curves for the detected serum MIRNAs. MiR-1281 and miR-126 showed the highest area under the curve (AUC) value in ROC curve analysis.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591993&req=5

pone.0139305.g003: ROC curves for serum miRNAs.Receiver operating characteristics (ROC) curves for the detected serum MIRNAs. MiR-1281 and miR-126 showed the highest area under the curve (AUC) value in ROC curve analysis.
Mentions: Validation was then performed in 83 serum samples for the aforementioned miRNAs. C. elegans miR-39 values were similar in both groups (PSC and CC) (S1 Fig). Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC (Figs 1 and 2 (miR-1281, miR-126) and S2–S4 Figs (miR-26a, miR-30b, miR-122)). MiR-1281, miR-126, and miR-26a displayed higher levels in patients with PSC. In addition, miR-30b and miR-122 were also upregulated in patients with PSC, while miR-194 showed no significant difference. All the validated serum miRNAs were significantly higher in the study patients compared to healthy individuals. In order to compare the diagnostic potential of the different miRNAs a ROC curve analysis was performed. The area under the curve (AUC) values for the different miRNAs were as follows; MiR-1281 0.83 (95% confidence interval (CI) 0.72–0.91, p = 0.001), miR-126 0.87 (95% CI 0.77–0.94, p = 0.001), miR-26a 0.78 (95% CI 0.66–0.87, p = 0.001), miR-30b 0.78 (95% CI 0.67–0.87, p = 0.001) and miR-122 0.65 (95% CI 0.53–0.76, p = 0.032), respectively (Fig 3). The sensitivity and specificity values to distinguish between patients with PSC and CC are given in Table 1. A combination of the different miRNAs in a logistic regression model did not significantly improve the diagnostic accuracy (data not shown). Correlation analysis showed no correlation between the miRNAs and cholestatic parameters.

Bottom Line: All validated miRNAs were significantly lower in healthy individuals.MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile.Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; Integrated Research and Treatment Center-Transplantation (IFB-Tx), Hannover Medical School, Hannover, Germany.

ABSTRACT

Background and aim: Patients with primary sclerosing cholangitis (PSC) are at high risk for the development of cholangiocarcinoma (CC). Analysis of micro ribonucleic acid (MiRNA) patterns is an evolving research field in biliary pathophysiology with potential value in diagnosis and therapy. Our aim was to evaluate miRNA patterns in serum and bile of patients with PSC and/or CC.

Methods: Serum and bile from consecutive patients with PSC (n = 40 (serum), n = 52 (bile)), CC (n = 31 (serum), n = 19 (bile)) and patients with CC complicating PSC (PSC/CC) (n = 12 (bile)) were analyzed in a cross-sectional study between 2009 and 2012. As additional control serum samples from healthy individuals were analyzed (n = 12). The miRNA levels in serum and bile were determined with global miRNA profiling and subsequent miRNA-specific polymerase chain reaction-mediated validation.

Results: Serum analysis revealed significant differences for miR-1281 (p = 0.001), miR-126 (p = 0.001), miR-26a (p = 0.001), miR-30b (p = 0.001) and miR-122 (p = 0.034) between patients with PSC and patients with CC. All validated miRNAs were significantly lower in healthy individuals. MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) were significantly different between patients with PSC and PSC/CC in bile.

Conclusions: Patients with PSC and/or CC have distinct miRNA profiles in serum and bile. Furthermore, miRNA concentrations are different in bile of patients with CC on top of PSC indicating the potential diagnostic value of these miRNAs.

No MeSH data available.


Related in: MedlinePlus