Abstract
In transcriptomics, micro RNAs (miRNAs) has gained much interest especially as potential disease indicators. However, apart from holding a great promise related to their clinical application, a lot of inconsistent results have been published. Our aim was to compare the miRNA expression levels in ovarian cancer and healthy subjects using the Bayesian multilevel model and to assess their potential usefulness in diagnosis. We have analyzed a case-control observational data on expression profiling of 49 preselected miRNA-based ovarian cancer indicators in 119 controls and 59 patients. A Bayesian multilevel model was used to characterize the effect of disease on miRNA levels controlling for differences in age and body weight. The difference between the miRNA level and health status of the patient on the scale of the data variability were discussed in the context of their potential usefulness in diagnosis. Additionally, the cross-validated area under the ROC curve (AUC) was used to assess the expected out-of-sample discrimination index of a different sets of miRNAs. The proposed model allowed us to describe the set of miRNA levels in patients and controls. Three highly correlated miRNAs: miR-101-3p, miR-142-5p, miR-148a-3p rank the highest with almost identical effect sizes that ranges from 0.45 to 1.0. For those miRNAs the credible interval for AUC ranged from 0.63 to 0.67 indicating their limited discrimination potential. A little benefit in adding information from other miRNAs was observed. There were several miRNAs in the dataset (miR-604, hsa-miR-221-5p) for which inferences were uncertain. For those miRNAs more experimental effort is needed to fully assess their effect in the context of new hits discovery and usefulness as disease indicators. The proposed multilevel Bayesian model can be used to characterize the panel of miRNA profile and to assess the difference in expression levels between healthy and cancer individuals.
Highlights
IntroductionBayesian modeling of micro RNA regulate gene expression post-transcriptionally by affecting the translation of target messenger RNAs (mRNAs) [1]
Regulate gene expression post-transcriptionally by affecting the translation of target messenger RNAs [1]. mRNA target recognition by a single miRNA is found in different regions of mRNA, in the 3’ untranslated region (3’UTR), 5’ untranslated region (5’UTR) and in the coding sequences [2], depending solely on a complementarity with the 6–8 50 nucleotides of the miRNAs
The whole study design initialized with the determination of 752 miRNA levels in 59 samples: (i) control (n = 16), (ii) ovarian cancer with no BRCA1/2 mutation (-/-) (n = 33) and (iii) ovarian cancer with BRCA1 or BRCA2 mutation (+/+) (n = 10)
Summary
Bayesian modeling of micro RNA regulate gene expression post-transcriptionally by affecting the translation of target messenger RNAs (mRNAs) [1]. MRNA target recognition by a single miRNA is found in different regions of mRNA, in the 3’ untranslated region (3’UTR), 5’ untranslated region (5’UTR) and in the coding sequences [2], depending solely on a complementarity with the 6–8 50 nucleotides of the miRNAs. The same miRNA may have different effects on the same disease. A single miRNA can affect hundreds of mRNA targets acting as oncogenes or tumor suppressors in a cellular-dependent context and depending on the genes targeted [3, 4]. Accumulated evidences have shown that miRNA expression is altered in most types of cancer being involved in a regulation of a wide range of developmental, physiological and cellular processes e.g. proliferation, adhesion, apoptosis and angiogenesis [5]. A lot of effort has been paid towards searching for promising miRNA hits for diagnosis and treatment of various types of cancer e.g. breast cancer [6], leukemia [7,8], liver cancer [9,10], ovarian cancer [11], pancreatic and prostate cancer [12,13], and other diseases as well (cardiovascular, metabolic diseases, neurodegenerative disorders) [14,15,16]
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