Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Zatelli, Maria Chiara; Grossrubatscher, Erika; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

doi:10.1530/erc-17-0091

Cited by 40 publications

(45 citation statements)

References 124 publications

(111 reference statements)

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“…MiRs are involved in various aspects of cellular function, normal pancreas development, islet differentiation, or pancreatic tumorigenesis [18], and represent potential prognostic markers in NET [19]. For identification of miRs we subjected total RNA samples of untreated BON, QGP, and NT-3 cells to next-generation sequencing (NGS) analysis.…”

Section: Identification Of Mirs Expressed In Bon and Qgp Cellsmentioning

confidence: 99%

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Luley

Biedermann

Künstner

et al. 2020

Cancers

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Experimental models of neuroendocrine tumor disease are scarce, with only a few existing neuroendocrine tumor cell lines of pancreatic origin (panNET). Their molecular characterization has so far focused on the neuroendocrine phenotype and cancer-related mutations, while a transcription-based assessment of their developmental origin and malignant potential is lacking. In this study, we performed immunoblotting and qPCR analysis of neuroendocrine, epithelial, developmental endocrine-related genes as well as next-generation sequencing (NGS) analysis of microRNAs (miRs) on three panNET cell lines, BON-1, QGP-1, and NT-3. All three lines displayed a neuroendocrine and epithelial phenotype; however, while insulinoma-derived NT-3 cells preferentially expressed markers of mature functional pancreatic β-cells (i.e., INS, MAFA), both BON-1 and QGP-1 displayed high expression of genes associated with immature or non-functional β/δ-cells genes (i.e., NEUROG3), or pancreatic endocrine progenitors (i.e., FOXA2). NGS-based identification of miRs in BON-1 and QGP-1 cells revealed the presence of all six members of the miR-17-92 cluster, which have been implicated in β-cell function and differentiation, but also have roles in cancer being both oncogenic or tumor suppressive. Notably, both BON-1 and QGP-1 cells expressed several miRs known to be negatively associated with epithelial-mesenchymal transition, invasion or metastasis. Moreover, both cell lines failed to exhibit migratory activity in vitro.Cancers 2020, 12, 691 2 of 18 Taken together, NT-3 cells resemble mature functional β-cells, while both BON-1 and QGP-1 are more similar to immature/non-functional pancreatic β/δ-cells or pancreatic endocrine progenitors. Based on the recent identification of three transcriptional subtypes in panNETs, NT-3 cells resemble the "islet/insulinoma tumors" (IT) subtype, while BON-1 and QGP-1 cells were tentatively classified as "metastasis-like/primary" (MLP). Our results provide a comprehensive characterization of three panNET cell lines and demonstrate their relevance as neuroendocrine tumor models.

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Section: Identification Of Mirs Expressed In Bon and Qgp Cellsmentioning

confidence: 99%

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Luley

Biedermann

Künstner

et al. 2020

Cancers

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“…Recently, a high focus on liquid biomarkers to select patients who will benefit from different types of treatments has emerged [77]. The available literature data clearly show that tissue miRNA profiling may potentially represent a prognostic biomarker in NEN [78]. However, the role of circulating miRNA in these settings is far from being consolidated and very little is known about the role of microRNA in tissue and blood in patients with GEP NEC.…”

Section: Biomarkersmentioning

confidence: 99%

Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)

et al. 2018

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Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.

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“…Further studies are required to evaluate the application of miRNAs as clinical and therapeutic markers in NENs. This issue is extensively reviewed in recent publications (Zatelli et al 2017, Zimmermann et al 2018, Rizzo & Meyer 2018, Panarelli et al 2019).…”

Section: Rna Markersmentioning

confidence: 99%

“…CTCs have been associated with higher tumor grade and burden, increased circulating CgA, Ki67 index and worse PFS and OS in grade 1-2 NENs (Khan et al 2011(Khan et al , 2013. Measurement and molecular characterization of CTCs may be helpful to stratify patients for specific therapies in the future (Khan et al 2011, Zatelli et al 2017. However, the sensitivity of CTCs varies according to the NEN type, and CTCs are not specific for any subgroup of tumors .…”

Section: Circulating Tumor Endothelial and White Cellsmentioning

confidence: 99%

Neuroendocrine neoplasms: current and potential diagnostic, predictive and prognostic markers

Herrera‐Martínez

Hofland

Moreno

et al. 2019

Endocrine-Related Cancer

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Some biomarkers for functioning and non-functioning neuroendocrine neoplasms (NENs) are currently available. Despite their application in clinical practice, results should be interpreted cautiously. Considering the variable sensitivity and specificity of these parameters, there is an unmet need for novel biomarkers to improve diagnosis and predict patient outcome. Nowadays, several new biomarkers are being evaluated and may become future tools for the management of NENs. These biomarkers include (1) peptides and growth factors; (2) DNA and RNA markers based on genomics analysis, for example, the so-called NET test, which has been developed for analyzing gene transcripts in circulating blood; (3) circulating tumor/endothelial/progenitor cells or cell-free tumor DNA, which represent minimally invasive methods that would provide additional information for monitoring treatment response and (4) improved imaging techniques with novel radiolabeled somatostatin analogs or peptides. Below we summarize some future directions in the development of novel diagnostic and predictive/prognostic biomarkers in NENs. This review is focused on circulating and selected tissue markers.

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Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms

Cited by 40 publications

References 124 publications

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

A Comprehensive Molecular Characterization of the Pancreatic Neuroendocrine Tumor Cell Lines BON-1 and QGP-1

Unmet Needs in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms (WHO G3)

Neuroendocrine neoplasms: current and potential diagnostic, predictive and prognostic markers

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