Analysis of miR-29 Serum Levels in Patients with Neuroendocrine Tumors—Results from an Exploratory Study

Abstract

Background and aims: Due to its involvement in tumor biology as well as tumor-associated stroma cell responses, recent data suggested a potential role of miR-29 as a biomarker for different malignancies. However, its role in neuroendocrine tumors (NETs) is only poorly understood. Methods: We measured circulating levels of miR-29b in 45 patients with NET and compared them to 19 healthy controls. Results were correlated with clinical records. Results: In our cohort of NET patients treated between 2010 and 2019 at our department, miR-29b serum levels were significantly downregulated when compared to healthy control samples. Further, a significant correlation between chromogranin A (CgA) and relative miR-29b levels was noted. However, serum levels of miR-29b were independent of tumor-related factors such as proliferation activity according to Ki-67 index, tumor grading, the TMN stage of malignant tumors, somatostatin receptor expression or clinical features such as functional or non-functional disease and presence of tumor relapse. Finally, in contrast to previous results from other malignancies, miR-29b serum levels were not a significant predictor of overall survival in NET patients. Conclusion: Our data suggest a role for miR-29b serum levels as a previously unrecognized biomarker for diagnosis of NET. However, miR-29 does not allow for predicting tumor stage or patients’ outcome.

MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations

“…Their data suggest a role for serum miRNA-29b levels as a previously unrecognized biomarker for the diagnosis of NENs. However, miRNA-29 does not predict tumor stage or patient outcome [65].…”

The Role of miRNA in the Pathophysiology of Neuroendocrine Tumors

“…Again, these cells were sensitive towards AKT/PI3K/mTOR inhibition, showing that some findings from alternate tumor entities do indeed translate to NET. This was additionally proven by Özdirik et al, as an evaluation of serum miR-29b in patients showed a similar correlation with chromogranin A levels in NET, while not corresponding with Ki-67 index, tumor grading, TMN stage, or overall survival [154].…”

“…No correlation of miR-223 levels to clinical or histopathological factors was observed, nor did the miRNA have any prognostic function [30]. However, in the analysis of miR-29 serum levels in patients with NETs, a significant correlation between chromogranin A (CgA) and relative miR-29b levels was found [154].…”

“…Furthermore, upregulation of PTTG1 was found together with decreased miR-186 expression, suggesting that the upregulation of PTTG1 is induced by loss of miR-186 [198]. Interestingly, significantly lower levels of circulating miR-223 [30] and miR-29 [154] were found in patients with gastroenteropancreatic NET, with primary tumors located in the ileum (n = 23), pancreas (n = 21), and stomach (n = 1), as compared to healthy individuals (n = 19), suggesting a circulating mRNA pattern, which overlaps different origins of NET. No correlation of miR-223 levels to clinical or histopathological factors was observed, nor did the miRNA have any prognostic function [30].…”

Clinical Challenges in the Management of Neuroendocrine Tumors

“…Two studies focused on diagnostic work in relation to NETs: Özdirik et al [ 5 ] suggested a potential diagnostic role for miR-29b serum levels as a novel biomarker for the diagnosis of NET, whereas Zhao et al [ 6 ] summarized the procedures commonly used to visualize small insulinomas, with particular effort focused on the contribution of selective arterial calcium stimulation and hepatic venous sampling.…”