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Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.

Becker PP, Rau M, Schmitt J, Malsch C, Hammer C, Bantel H, Müllhaupt B, Geier A - PLoS ONE (2015)

Bottom Line: Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH.Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich (USZ), Zürich, Switzerland.

ABSTRACT

Objectives: Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.

Methods: Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.

Results: The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).

Conclusions: Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.

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Related in: MedlinePlus

Correlation between different circulating microRNA levels and other serum parameters.MiR-122 and miR-192 showed a very similar profile in the different patient groups; their correlation was highly significant (A). Correlation was also analyzed in comparison to the routine serum parameters ALT and CK18-Asp396. MicroRNAs -122, and -192 could be positively correlated with ALT and CK-18 (B, C, E, F). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (D). Detailed results are displayed in S1 Table. Correlation between variables was calculated using Spearman’s Rank correlation test.
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pone.0142661.g003: Correlation between different circulating microRNA levels and other serum parameters.MiR-122 and miR-192 showed a very similar profile in the different patient groups; their correlation was highly significant (A). Correlation was also analyzed in comparison to the routine serum parameters ALT and CK18-Asp396. MicroRNAs -122, and -192 could be positively correlated with ALT and CK-18 (B, C, E, F). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (D). Detailed results are displayed in S1 Table. Correlation between variables was calculated using Spearman’s Rank correlation test.

Mentions: In a next step detected miRNA profiles were correlated to available routine serum parameters such as ALT and CK18-Asp396 fragments (Fig 3). As miR-122 and miR-192 showed a very similar profile pattern in the different patient groups, their correlation was highly significant (R = 0.83, p< 0.0001, Fig 3). Both had a significant and positive correlation with serum ALT (miR-122: R = 0.53, p< 0.0001; miR-192: R = 0.45, p< 0.0001) (Fig 3). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (Fig 3, S3 Fig). Again, a positive and significant correlation of CK18-Asp396 fragments to respective miRNA levels has been observed (miR-122: R = 0.48, p< 0.0001; miR-192: R = 0.36, p< 0.0001) (Fig 3). For miR-21 a positive significant correlation could be shown to ALT level but no correlation to CK18-Asp396 or other miRNAs could be determined (S1 Table). For miRs-21, -122 and -192 profile levels were also correlated with single NAS parameters (degree of steatosis, ballooning, lobular inflammation and fibrosis). A relevant correlation of all individual miR levels could be detected in comparison to the degree of steatosis. Also, a significant correlation of lobular inflammation to miR-21 and miR-122 could be found (S1 Table).


Performance of Serum microRNAs -122, -192 and -21 as Biomarkers in Patients with Non-Alcoholic Steatohepatitis.

Becker PP, Rau M, Schmitt J, Malsch C, Hammer C, Bantel H, Müllhaupt B, Geier A - PLoS ONE (2015)

Correlation between different circulating microRNA levels and other serum parameters.MiR-122 and miR-192 showed a very similar profile in the different patient groups; their correlation was highly significant (A). Correlation was also analyzed in comparison to the routine serum parameters ALT and CK18-Asp396. MicroRNAs -122, and -192 could be positively correlated with ALT and CK-18 (B, C, E, F). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (D). Detailed results are displayed in S1 Table. Correlation between variables was calculated using Spearman’s Rank correlation test.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643880&req=5

pone.0142661.g003: Correlation between different circulating microRNA levels and other serum parameters.MiR-122 and miR-192 showed a very similar profile in the different patient groups; their correlation was highly significant (A). Correlation was also analyzed in comparison to the routine serum parameters ALT and CK18-Asp396. MicroRNAs -122, and -192 could be positively correlated with ALT and CK-18 (B, C, E, F). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (D). Detailed results are displayed in S1 Table. Correlation between variables was calculated using Spearman’s Rank correlation test.
Mentions: In a next step detected miRNA profiles were correlated to available routine serum parameters such as ALT and CK18-Asp396 fragments (Fig 3). As miR-122 and miR-192 showed a very similar profile pattern in the different patient groups, their correlation was highly significant (R = 0.83, p< 0.0001, Fig 3). Both had a significant and positive correlation with serum ALT (miR-122: R = 0.53, p< 0.0001; miR-192: R = 0.45, p< 0.0001) (Fig 3). CK18-Asp396 fragment levels increased with the development of bland steatosis and the progression to NASH (Fig 3, S3 Fig). Again, a positive and significant correlation of CK18-Asp396 fragments to respective miRNA levels has been observed (miR-122: R = 0.48, p< 0.0001; miR-192: R = 0.36, p< 0.0001) (Fig 3). For miR-21 a positive significant correlation could be shown to ALT level but no correlation to CK18-Asp396 or other miRNAs could be determined (S1 Table). For miRs-21, -122 and -192 profile levels were also correlated with single NAS parameters (degree of steatosis, ballooning, lobular inflammation and fibrosis). A relevant correlation of all individual miR levels could be detected in comparison to the degree of steatosis. Also, a significant correlation of lobular inflammation to miR-21 and miR-122 could be found (S1 Table).

Bottom Line: Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH.Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Hepatology, University Hospital Zürich (USZ), Zürich, Switzerland.

ABSTRACT

Objectives: Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.

Methods: Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.

Results: The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).

Conclusions: Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.

Show MeSH
Related in: MedlinePlus