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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

MiRNA analysis in bile.Bile validation analysis for patients with primary sclerosing cholangitis (PSC) (n = 52), cholangiocarcinoma (CC) complicating PSC (PSC/CC) (n = 12) and CC (n = 19) revealed significant differences for the different miRNAs. MiR-1537 (A), miR-412 (B), miR-640 (C) and miR-3189 (D) were differentially expressed in patients with PSC and PSC/CC.
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pone.0139305.g004: MiRNA analysis in bile.Bile validation analysis for patients with primary sclerosing cholangitis (PSC) (n = 52), cholangiocarcinoma (CC) complicating PSC (PSC/CC) (n = 12) and CC (n = 19) revealed significant differences for the different miRNAs. MiR-1537 (A), miR-412 (B), miR-640 (C) and miR-3189 (D) were differentially expressed in patients with PSC and PSC/CC.

Mentions: C. elegans miR-39 values were equal in both groups (S5 Fig). Validation in 83 bile samples revealed significant differences for the investigated miRNAs (Fig 4 and S6 Fig). All miRNAs were significantly higher in patients with PSC or PSC/CC compared to patients with CC (p ≤ 0.05). MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) showed a significant difference between patients with PSC and PSC/CC. ROC curve analysis for the comparison between PSC and PSC/CC for the aforementioned miRNAs displayed the following AUC values; MiR-412 0.81 (95% CI 0.69–0.9, p = 0.001), miR-640 0.81 (95% CI 0.69–0.9, p = 0.001), miR-1537 0.78 (95% CI 0.66–0.87, p = 0.003) and miR-3189 0.8 (95% CI 0.68–0.89, p = 0.001). The sensitivity and specificity values to distinguish between patients with PSC and PSC/CC are highlighted in Table 4. The combination of miR-1537 and CA 19–9 in a logistic regression model resulted in an AUC value of 0.91 (95% CI 0.80–0.97, p = 0.001) with a sensitivity of 73% and a specificity of 93%, respectively. Eight out of eleven patients with PSC/CC were correctly classified (one missing CA 19–9 value). Comparison of ROC curves for miR-1537 and CA 19–9 vs. CA 19–9 alone showed a higher AUC value for the combination (0.91 vs. 0.88; p > 0.05). No correlation was found for the miRNAs and cholestatic parameters (S5 Table).


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)

MiRNA analysis in bile.Bile validation analysis for patients with primary sclerosing cholangitis (PSC) (n = 52), cholangiocarcinoma (CC) complicating PSC (PSC/CC) (n = 12) and CC (n = 19) revealed significant differences for the different miRNAs. MiR-1537 (A), miR-412 (B), miR-640 (C) and miR-3189 (D) were differentially expressed in patients with PSC and PSC/CC.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139305.g004: MiRNA analysis in bile.Bile validation analysis for patients with primary sclerosing cholangitis (PSC) (n = 52), cholangiocarcinoma (CC) complicating PSC (PSC/CC) (n = 12) and CC (n = 19) revealed significant differences for the different miRNAs. MiR-1537 (A), miR-412 (B), miR-640 (C) and miR-3189 (D) were differentially expressed in patients with PSC and PSC/CC.
Mentions: C. elegans miR-39 values were equal in both groups (S5 Fig). Validation in 83 bile samples revealed significant differences for the investigated miRNAs (Fig 4 and S6 Fig). All miRNAs were significantly higher in patients with PSC or PSC/CC compared to patients with CC (p ≤ 0.05). MiR-412 (p = 0.001), miR-640 (p = 0.001), miR-1537 (p = 0.003) and miR-3189 (p = 0.001) showed a significant difference between patients with PSC and PSC/CC. ROC curve analysis for the comparison between PSC and PSC/CC for the aforementioned miRNAs displayed the following AUC values; MiR-412 0.81 (95% CI 0.69–0.9, p = 0.001), miR-640 0.81 (95% CI 0.69–0.9, p = 0.001), miR-1537 0.78 (95% CI 0.66–0.87, p = 0.003) and miR-3189 0.8 (95% CI 0.68–0.89, p = 0.001). The sensitivity and specificity values to distinguish between patients with PSC and PSC/CC are highlighted in Table 4. The combination of miR-1537 and CA 19–9 in a logistic regression model resulted in an AUC value of 0.91 (95% CI 0.80–0.97, p = 0.001) with a sensitivity of 73% and a specificity of 93%, respectively. Eight out of eleven patients with PSC/CC were correctly classified (one missing CA 19–9 value). Comparison of ROC curves for miR-1537 and CA 19–9 vs. CA 19–9 alone showed a higher AUC value for the combination (0.91 vs. 0.88; p > 0.05). No correlation was found for the miRNAs and cholestatic parameters (S5 Table).

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