“…In contrast to the findings of Miller et al [21], we did not find miR-200 to be significantly dysregulated. This might be explained by the differences in the stages of the tumors analyzed in the 2 studies.…”
Section: Discussioncontrasting
confidence: 99%
“…These facts make the miRNA-7-5p a potential biomarker for SINENs. Miller et al [21] tested 28 small-bowel neuroendocrine tumors and also identified miR-7-5p among the most upregulated miRNAs, which underscores our findings. Potential targets and regulators of the miR-7 include Yin Yang 1 (YY1), NF-kB/RELA, and cMyc [22][23][24].…”
Section: Discussionsupporting
confidence: 84%
“…Miller et al [21] found the miR-143-3p to be downregulated in metastases compared to the primary tumors. Most significantly, in agreement with their findings, we also report a greater decrease in miR-143-3p in the metastases compared to the primary tumors (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…A reduction in miR-143 levels would allow release of important oncogenes during SI-NEN progression. Miller et al [21] discuss that miR-143 targets FOSB and NUAK2, leading to the downregulation of these genes.…”
Background/Aims: Neuroendocrine neoplasms of the small intestine (SI-NENs) constitute 25-30% of all gastroenteropancreatic NEN. These tumors arise from enterochromaffin cells, and little is known about their microRNA (miRNA) expression. The purpose of this study was to characterize the expression of miRNAs in SI-NEN and to determine the potential of miRNAs as noninvasive blood-based biomarkers. Methods: miRNA was purified from 15 tumor and 7 control tissue samples, converted to cDNA, and applied to a miScript miRNA PCR. The small nucleolar RNA, SNORD95, was used as an endogenous control. Results: Microarray analysis revealed 7 miRNAs that showed a promising distinction between tumorous and healthy tissue. The miRNAs miR-7-5p and miR-96-5p were clearly upregulated in the tumor compared to the healthy tissue. In contrast, miRNAs miR-9-5p, miR-122-5p, miR-124-3p, miR-143-3p, and miR-144-3p showed a distinct downregulation in the tumor compared to the healthy tissue. These results were validated on a further 15 tumor samples, and the findings held true. As the miR-7-5p was significantly upregulated and revealed a low range across tumor samples, its presence was tested in the sera of 32 tumor patients and 25 healthy controls. Sera from all patients with SI-NENs had significantly higher levels of miR-7-5p than those from the 25 healthy controls (p = 0.0002), whereas there was no correlation with age, gender, or T-stage or UICC stage. Conclusion: The miRNA miR-7-5p may be a promising biomarker test for SI-NEN, which should be validated in a large-scale prospective study.
“…In contrast to the findings of Miller et al [21], we did not find miR-200 to be significantly dysregulated. This might be explained by the differences in the stages of the tumors analyzed in the 2 studies.…”
Section: Discussioncontrasting
confidence: 99%
“…These facts make the miRNA-7-5p a potential biomarker for SINENs. Miller et al [21] tested 28 small-bowel neuroendocrine tumors and also identified miR-7-5p among the most upregulated miRNAs, which underscores our findings. Potential targets and regulators of the miR-7 include Yin Yang 1 (YY1), NF-kB/RELA, and cMyc [22][23][24].…”
Section: Discussionsupporting
confidence: 84%
“…Miller et al [21] found the miR-143-3p to be downregulated in metastases compared to the primary tumors. Most significantly, in agreement with their findings, we also report a greater decrease in miR-143-3p in the metastases compared to the primary tumors (Fig.…”
Section: Discussionmentioning
confidence: 99%
“…A reduction in miR-143 levels would allow release of important oncogenes during SI-NEN progression. Miller et al [21] discuss that miR-143 targets FOSB and NUAK2, leading to the downregulation of these genes.…”
Background/Aims: Neuroendocrine neoplasms of the small intestine (SI-NENs) constitute 25-30% of all gastroenteropancreatic NEN. These tumors arise from enterochromaffin cells, and little is known about their microRNA (miRNA) expression. The purpose of this study was to characterize the expression of miRNAs in SI-NEN and to determine the potential of miRNAs as noninvasive blood-based biomarkers. Methods: miRNA was purified from 15 tumor and 7 control tissue samples, converted to cDNA, and applied to a miScript miRNA PCR. The small nucleolar RNA, SNORD95, was used as an endogenous control. Results: Microarray analysis revealed 7 miRNAs that showed a promising distinction between tumorous and healthy tissue. The miRNAs miR-7-5p and miR-96-5p were clearly upregulated in the tumor compared to the healthy tissue. In contrast, miRNAs miR-9-5p, miR-122-5p, miR-124-3p, miR-143-3p, and miR-144-3p showed a distinct downregulation in the tumor compared to the healthy tissue. These results were validated on a further 15 tumor samples, and the findings held true. As the miR-7-5p was significantly upregulated and revealed a low range across tumor samples, its presence was tested in the sera of 32 tumor patients and 25 healthy controls. Sera from all patients with SI-NENs had significantly higher levels of miR-7-5p than those from the 25 healthy controls (p = 0.0002), whereas there was no correlation with age, gender, or T-stage or UICC stage. Conclusion: The miRNA miR-7-5p may be a promising biomarker test for SI-NEN, which should be validated in a large-scale prospective study.
“…Moreover, when evaluating the association between the 11 selected miRNAs and clinical and carcinoid pathological characteristics, four miRNAs (miR-129-5p, miR-129*, miR-22 and miR-141) were found downregulated in high-stage tumors, four miRNAs (miR-129-5p, miR-409-3p, miR-409-5p and miR-431-5p) were found downregulated in cases with vascular invasion and three miRNAs (miR-409-3p, miR-409-5p and miR-431-5p) were found downregulated in tumors with lymph node metastases (Rapa et al 2015). Similarly, miRNA expression pattern in GEP NENs has been extensively investigated (Ruebel et al 2010, Matthaei et al 2012, Li et al 2013a, Dossing et al 2014, Miller et al 2016), but few studies evaluated a possible prognostic role of miRNAs in GEP NEN. Roldo and coworkers (Roldo et al 2006) evaluated the global miRNA expression in a series of 40 pNENs (28 nonfunctioning and 12 insulinomas) and found that miR-21 levels strongly associated with Ki67 labeling index and liver metastases.…”
The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue-and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs.
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