Dataset Information

MiRNA in Molecular Diagnostics.

ABSTRACT: MicroRNAs are a class of small non-coding RNA molecules that regulate gene expression on post-transcriptional level. Their biogenesis consists of a complex series of sequential processes, and they regulate expression of many genes involved in all cellular processes. Their function is essential for maintaining the homeostasis of a single cell; therefore, their aberrant expression contributes to development and progression of many diseases, especially malignant tumors and viral infections. Moreover, they can be associated with certain states of a specific disease, obtained in the least invasive manner for patients and analyzed with basic molecular methods used in clinical laboratories. Because of this, they have a promising potential to become very useful biomarkers and potential tools in personalized medicine approaches. In this review, miRNAs biogenesis, significance in cancer and infectious diseases, and current available test and methods for their detection are summarized.

SUBMITTER: Matulic M

PROVIDER: S-EPMC9495386 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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miRNA in Molecular Diagnostics.

Matulić Maja M Gršković Paula P Petrović Andreja A Begić Valerija V Harabajsa Suzana S Korać Petra P

Bioengineering (Basel, Switzerland) 20220909 9

MicroRNAs are a class of small non-coding RNA molecules that regulate gene expression on post-transcriptional level. Their biogenesis consists of a complex series of sequential processes, and they regulate expression of many genes involved in all cellular processes. Their function is essential for maintaining the homeostasis of a single cell; therefore, their aberrant expression contributes to development and progression of many diseases, especially malignant tumors and viral infections. Moreove ...[more]

PMID: 36135005

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Project description:The diagnosis of inflammatory bowel disease (IBD) still remains a clinical challenge and the most accurate diagnostic procedure is a combination of clinical tests including invasive endoscopy. In this study we evaluated whether systematic miRNA expression profiling, in conjunction with machine learning techniques, is suitable as a non-invasive test for the major IBD phenotypes (Crohn's disease (CD) and ulcerative colitis (UC)). Based on microarray technology, expression levels of 863 miRNAs were determined for whole blood samples from 40 CD and 36 UC patients and compared to data from 38 healthy controls (HC). To further discriminate between disease-specific and general inflammation we included miRNA expression data from other inflammatory diseases (inflammation controls (IC): 24 chronic obstructive pulmonary disease (COPD), 23 multiple sclerosis, 38 pancreatitis and 45 sarcoidosis cases) as well as 70 healthy controls from previous studies. Classification problems considering 2, 3 or 4 groups were solved using different types of penalized support vector machines (SVMs). The resulting models were assessed regarding sparsity and performance and a subset was selected for further investigation. Measured by the area under the ROC curve (AUC) the corresponding median holdout-validated accuracy was estimated as ranging from 0.75 to 1.00 (including IC) and 0.89 to 0.98 (excluding IC), respectively. In combination, the corresponding models provide tools for the distinction of CD and UC as well as CD, UC and HC with expected classification error rates of 3.1 and 3.3%, respectively. These results were obtained by incorporating not more than 16 distinct miRNAs. Validated target genes of these miRNAs have been previously described as being related to IBD. For others we observed significant enrichment for IBD susceptibility loci identified in earlier GWAS. These results suggest that the proposed miRNA signature is of relevance for the etiology of IBD. Its diagnostic value, however, should be further evaluated in large, independent, clinically well characterized cohorts.

Project description:Tremendous progress has recently been made in both molecular subgrouping, and the establishment of prognostic biomarkers for embryonal brain tumors, particularly medulloblastoma. Several prognostic biomarkers that were initially identified in retrospective cohorts of medulloblastoma, including MYC and MYCN amplification, nuclear β-catenin accumulation, and chromosome 17 aberrations have now been validated in clinical trials. Moreover, molecular subgroups based on distinct transcriptome profiles have been consistently reported from various groups on different platforms demonstrating that the concept of distinct medulloblastoma subgroups is very robust. Well-described subgroups of medulloblastomas include tumors showing wingless signaling pathway (Wnt) activation, and another characterized by sonic hedgehog pathway activity. Two or more additional subgroups were consistently reported to contain the vast majority of high-risk tumors, including most tumors with metastatic disease at diagnosis and/or large cell/anaplastic histology. Several years ago, atypical teratoid rhabdoid tumor (AT/RT) was recognized as a separate entity based on its distinct biology and particularly aggressive clinical behavior. These tumors may occur supra or infratentorially and are usually found to have genetic alterations of SMARCB1 (INI1/hSNF5), a tumor suppressor gene located on chromosome 22q. Subsequent loss of SMARCB1 protein expression comprises a relatively specific and sensitive diagnostic marker for AT/RT. For CNS primitive neuroectodermal tumors (CNS PNETs), a consistent finding has been that they are molecularly distinct from medulloblastoma. Furthermore, a distinct fraction of CNS PNETs with particularly poor prognosis only occurring in young children was delineated, which was previously labeled ependymoblastoma or embryonal tumor with abundant neuropil and true rosettes (ETANTR) and which is morphologically characterized by the presence of multilayered "ependymoblastic" rosettes. This group of tumors shows a unique cytogenetic abnormality not seen in other brain tumors: focal amplification of a micro-RNA cluster at chromosome 19q13.42, which has never been found to be amplified in other CNS PNETs, medulloblastoma or AT/RT. In summary, these consistent findings have significantly contributed to our ability to sub-classify embryonal brain tumors into clinically and biologically meaningful strata and, for some of the subgroups, have led to the identification of specific targets for future development of molecularly targeted therapies.

Dataset Information

MiRNA in Molecular Diagnostics.

Publications

miRNA in Molecular Diagnostics.

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