MicroRNAs: A Puzzling Tool in Cancer Diagnostics and Therapy

D’Angelo, Barbara; Benedetti, Elisabetta; Cimini, Annamaria; Giordano, Antonio

doi:10.21873/anticanres.11142

Cited by 86 publications

(58 citation statements)

References 50 publications

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“…They are very stable and can easily be recovered from cell lines, fresh tissue, formalin-fixed paraffin embedded (FFPE) tissue, plasma, serum, urine, stool and other fluids [15,16]. miRNAs have an important role in biological processes, such as apoptosis, metabolism, cell growth and differentiation, and they regulate gene expression at the posttranscription level [17]. The deregulation of miRNAs can be a result of gene mutations, epigenetic modifications or deficiency in the miRNA processing pathway [17], and it can result in the development of human diseases, including cancer.…”

Section: Diagnosismentioning

confidence: 99%

miRNA analysis in pancreatic cancer: the Dartmouth experience

Abreu

Tsongalis

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%-90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm.

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Section: Diagnosismentioning

confidence: 99%

miRNA analysis in pancreatic cancer: the Dartmouth experience

Abreu

Tsongalis

2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…In particular, the most problematic issues reflect the scientific limitations of the detection strategies and the paucity of samples in validation sets that have not been adequately justified by power analysis [84, 92]. Given the discordance between reported signatures as well as the differences between tumor and circulating levels (particularly downregulation in the blood), the introduction of optimization and standardization procedures is a critical requirement in miRNA studies [104]. To ensure the future utilization of miRNAs as a clinically useful biomarker in cancer management, miRNA-based research will need to comply with core established guidelines including the Biospecimen Reporting for Improved Study Quality (BRISQ) or Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK) [105-107] and Standards for Reporting of Diagnostic Accuracy (STARD) [108].…”

Section: Current Statusmentioning

confidence: 99%

A Comprehensive Assessment of the Role of miRNAs as Biomarkers in Gastroenteropancreatic Neuroendocrine Tumors

et al. 2018

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Background/Aims: A key issue in neuroendocrine neoplasia management is the identification of blood signatures that specifically define the activity of a cancer or local tumor microenvironment. MicroRNAs (miRNAs) may represent such a candidate. To evaluate their clinical utility as biomarkers in gastroenteropancreatic neuroendocrine tumors (GEP-NETs), we assessed their expression in tissue and blood. Methods: A systematic review of PubMed was undertaken to identify studies investigating miRNAs in GEP-NETs and their utility as blood or tissue biomarkers. Results: Twenty-two studies using a range of methodologies with different normalization protocols were identified: tumor – gastric NET type 1 (n = 1 study: MiR-222, regulates p27KIP1), pancreatic (n = 6: MiR-21 [inflammatory marker, oncogene] and MiR-144 [PI₃K/AKT signaling], both up- and downregulated depending on the method), small intestinal (n = 7: no consistent signature), and colorectal (n = 3: no consistent signature); blood – gastric NET type 1 (n = 1: MiR-222), pancreatic (n = 3: MiR-21), and small intestinal (n = 3: no consistent signature). The studies all included heterogeneous cohorts, were insufficiently powered, and utilized different methodologies, and age- and gender-matched controls were not used. Different miRNA isolation methods and detection protocols resulted in inconsistent expression comparing tumor and blood. A scientific discrepancy was the downregulated expression of some circulating candidates compared to tissue levels, suggesting methodological issues or physiological responses to the tumor. Both are of concern in defining the biometrics of a marker. Conclusions: A potential biomarker for GEP-NETs included MiR-21 (small bowel and pancreas), but this epithelial tumor marker requires prospective validation. Overall, significant scientific investigation remains to identify and demonstrate neuroendocrine specificity and to validate candidate miRNA biomarkers.

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“…In comparison to small inhibitor molecules, miRNAs can target MMPs more selectively without the interference of the structural similarities of MMP catalytic domains (23). signaling pathways critical for a malignant tumor behavior (49). Accordingly, the comprehensive characterization of miRNAs involved in a regulation of MMPs and their suppressors in cancer cells might greatly inform new drug trials and constitutes a first step toward the development of new anticancer therapeutic approaches (50).…”

Section: Cancer Genomics and Proteomicsmentioning

confidence: 99%