LITERATURE UPDATE


(miRNAs). miRNAs are small non-coding RNAs that regulate gene expression and have been implicated in many diseases, including T2D and cancer. To begin, the authors conducted


a literature review to identify miRNAs associated with the PC-T2D link, but found only limited research on this specific association, with most studies focusing on the antitumour effects of metformin. Furthermore, they performed a bioinformatics analysis to identify new potential miRNAs that might be relevant in the context of PC-T2D.


First, they identified miRNAs and gene expression alterations common to both diseases using publicly available datasets. Subsequently, they performed an integrative analysis between the identified miRNAs and genes alterations. As a result, they identified nine miRNAs that could potentially play an important role in the interplay between PC and T2D.


These miRNAs have the potential to influence nearby cells and distant tissues, affecting critical processes like extracellular matrix remodeling and cell adhesion, ultimately contributing to the development of T2D or PC. Taken together, these analyses underscore the importance of further exploring the role of miRNAs in the complex interplay of PC and T2D.


Advancing gastrointestinal cancer diagnostics: a systematic review and meta-analysis of circulating microRNA-1246 as a non-invasive biomarker


Aalami AH, Shahriari A, Mazaheri M, Aalami F, Sahebkar A. Biomarkers. 2024 Jul; 29 (5): 233–43. doi: 10.1080/ 1354750X.2024.2350714.


Despite numerous reports on the alterations of microRNA-1246 (miR-1246) expression level in digestive system cancers, its role in gastrointestinal cancers (GICs) remains unclear. This meta-analysis aimed to assess the diagnostic potential of circulating miR- 1246 in GICs.


Meta-disc version 1.4 and


Comprehensive Meta-Analysis (CMA) version 3.7 software were used to calculate pooled sensitivity, specificity, likelihood ratios, diagnostic odds ratio (DOR), area under the curve (AUC), Q*index and summary receiver-operating characteristic (SROC). Subgroup analyses were conducted for cancer type, sample type and geographical region. Publication bias was assessed using Begg’s and Egger’s tests.


A total of 14 articles involving 18 studies and 1526 participants (972 cases


50


and 554 controls) were included. The diagnostic accuracy of miRNA-1246 in GICs was as follows: pooled sensitivity: 0.81 (95% CI: 0.79– 0.83), specificity: 0.74 (95% CI: 0.71– 0.77), PLR: 3.315 (95% CI: 2.33– 4.72), NLR: 0.221 (95% CI: 0.153– 0.319), DOR: 16.87 (95% CI: 9.45–30.09), AUC: 0.891, and Q*-index: 0.807. No publication bias was found based on Begg’s (P = 0.172) and Egger’s (P = 0.113) tests. In conclusion, circulating miR-1246


shows promise as a non-invasive biomarker for early detection of GICs.


MicroRNA Expression in Endometrial Cancer: Current Knowledge and Therapeutic Implications Iavarone I, Molitierno R, Fumiento P et al. Medicina (Kaunas). 2024 Mar 15; 60 (3): 486. doi: 10.3390/ medicina60030486.


An extracellular vesicle is part of a class of submicron particles derived from cells, mediating cellular crosstalk through microRNA (miRNA). MiRNA is a group of RNA molecules, each of which consists of 15–22 nucleotides and post- transcriptionally modulates gene expression. The complementary mRNAs – onto which the miRNAs hybridise – are involved in processes such as implantation, tumour suppression, proliferation, angiogenesis, and metastasis that define the entire tumour microenvironment. The endometrial biopsy is a standard technique used to recognise cellular atypia, but other non-invasive markers may reduce patient discomfort during the use of invasive methods. The present study aims to examine the distribution and the regulation of the differentially expressed miRNAs (DEMs) and EV-derived substances in women with endometrial cancer.


The authors systematically


searched the PubMed, EMBASE, Scopus, Cochrane Library, and ScienceDirect databases in April 2023, adopted the string “Endometrial Neoplasms AND Exosomes”, and followed the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. They selected all the studies that included patients with endometrial cancer and that described the regulation of miRNA molecules in that context. The differences in molecule expression between patients and controls were evaluated as significant when the proteins had a fold change of ±1.5.


Seventeen records fulfilled the


inclusion criteria: a total of 371 patients and 273 controls were analysed. The upregulated molecules that had the widest delta between endometrial cancer patients and controls-relative expression ≥ 1 > 3 log2(ratio)-were miR-20b-5p, miR-204-5p, miR-15a-5p, and miR-320a. In particular, miR-20b-5p and miR-204- 5p were extracted from both serum and endometrial specimens, whereas miR- 15a-5p was only isolated from plasma, and miR-320a was only extracted from the endometrial specimens. In parallel, the most downregulated miRNA in the endometrial cancer patients compared to the healthy subjects was miR-320a, which was found in the endometrial specimens.


Although their epigenetic


regulation remains unknown, these upregulated molecules derived from EVs are feasible markers for the early detection of endometrial cancer. The modulation of these miRNA molecules should be assessed during different treatments or if recurrence develops in response to a targeted treatment modality.


MicroRNAs in Pancreatic Cancer: Advances in Biomarker Discovery and Therapeutic Implications Madadjim R, An T, Cui J. Int J Mol Sci. 2024 Mar 31; 25 (7): 3914. doi: 10.3390/ ijms25073914.


Pancreatic cancer remains a formidable malignancy characterised by high mortality rates, primarily attributable to late-stage diagnosis and a dearth of effective therapeutic interventions. The identification of reliable biomarkers holds paramount importance in enhancing early detection, prognostic evaluation, and targeted treatment modalities.


Small non-coding RNAs, particularly


microRNAs, have emerged as promising candidates for pancreatic cancer biomarkers in recent years. In this review, the authors delve into the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. Drawing upon the latest research advancements in omics data-driven biomarker discovery, they also perform a case study using public datasets and address commonly identified research discrepancies, challenges, and limitations. Lastly, they discuss analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, presenting new insights into identifying robust miRNA- centric biomarkers.


DECEMBER 2024 WWW.PATHOLOGYINPRACTICE.COM


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