The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features

Herrera‐Martínez, Aura D.; Gahete, Manuel D.; Sánchez‐Sánchez, Rafael; Salas, Rosa Ortega; Serrano‐Blanch, Raquel; Salvatierra, A.; Hofland, Leo J.; Luque, Raúl M.; Gálvez-Moreno, María Ángeles; Castaño, Justo P.

doi:10.1016/j.lungcan.2017.05.006

Cited by 15 publications

(15 citation statements)

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“…Although expression of canonical ghrelin has been described in various tumor types, its potential role in cancer is still controversial 48 , 49 . Ghrelin has been described in NETs using immunohistochemistry and qPCR 22 , 25 , 42 , 43 , in our cohort ghrelin was expressed in NET samples, albeit in substantially lower amounts than in normal tissues. In addition, in our cohort ghrelin expression levels were higher in PNETs than in GI-NETs, which is consistent with previous evidence 43 but differed from other reports 44 .…”

Section: Resultssupporting

confidence: 47%

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Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in Gastroenteropancreatic Neuroendocrine Tumors

Herrera‐Martínez

Gahete

Sánchez‐Sánchez

et al. 2018

Clinical and Translational Gastroenterology

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ObjectivesThe association between the presence and alterations of the components of the ghrelin system and the development and progression of neuroendocrine tumors (NETs) is still controversial and remains unclear.MethodsHere, we systematically evaluated the expression levels (by quantitative-PCR) of key ghrelin system components of in gastroenteropancreatic (GEP)-NETs, as compared to non-tumor adjacent (NTA; n = 42) and normal tissues (NT; n = 14). Then, we analyzed their putative associations with clinical-histological characteristics.ResultsThe results indicate that ghrelin and its receptor GHSR1a are present in a high proportion of normal tissues, while the enzyme ghrelin-O-acyltransferase (GOAT) and the splicing variants In1-ghrelin and GHSR1b were present in a lower proportion of normal tissues. In contrast, all ghrelin system components were present in a high proportion of tumor and NTA tissues. GOAT was significantly overexpressed (by quantitative-PCR (qPCR)) in tumor samples compared to NTA, while a trend was found for ghrelin, In1-ghrelin and GHSR1a. In addition, expression of these components displayed significant correlations with key clinical parameters. The marked overexpression of GOAT in tumor samples compared to NTA regions was confirmed by IHC, revealing that this enzyme is particularly overexpressed in gastrointestinal NETs, where it is directly correlated with tumor diameter.ConclusionsThese results provide novel information on the presence and potential pathophysiological implications of the ghrelin system components in GEP-NETs, wherein GOAT might represent a novel diagnostic biomarker.

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Section: Resultssupporting

confidence: 47%

“…Quantification of the recovered RNA was assessed using NanoDrop2000 spectrophotometer (Thermo Scientific, Wilmington, NC). Total RNA was retrotranscribed to cDNA with the First-Strand Synthesis kit using random hexamer primers (Thermo Scientific) as previously reported 25 – 28 …”

Section: Methodsmentioning

confidence: 99%

Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in Gastroenteropancreatic Neuroendocrine Tumors

Herrera‐Martínez

Gahete

Sánchez‐Sánchez

et al. 2018

Clinical and Translational Gastroenterology

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“…Using the rabbit mAb UMB-7 ( Table 3 ), SST 1 expression was confirmed in prostate adenocarcinomas, rhabdomyosarcoma and liposarcoma, pituitary somatotroph adenomas, pancreatic adenocarcinoma, stomach cancer, urinary bladder cancer, pheochromocytoma, GI neuroendocrine tumors (NETs), breast carcinoma, cervix carcinoma, and ovarian tumors ( Lupp et al, 2013 ). SST 1 was abundantly expressed in bronchopulmonary NETs ( Herrera-Martinez et al, 2017b ) and positively associated with patient survival ( Kaemmerer et al, 2015a ).…”

Section: Somatostatin Receptormentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

et al. 2018

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Somatostatin, also known as somatotropin-release inhibitory factor, is a cyclopeptide that exerts potent inhibitory actions on hormone secretion and neuronal excitability. Its physiologic functions are mediated by five G protein–coupled receptors (GPCRs) called somatostatin receptor (SST)1–5. These five receptors share common structural features and signaling mechanisms but differ in their cellular and subcellular localization and mode of regulation. SST2 and SST5 receptors have evolved as primary targets for pharmacological treatment of pituitary adenomas and neuroendocrine tumors. In addition, SST2 is a prototypical GPCR for the development of peptide-based radiopharmaceuticals for diagnostic and therapeutic interventions. This review article summarizes findings published in the last 25 years on the physiology, pharmacology, and clinical applications related to SSTs. We also discuss potential future developments and propose a new nomenclature.

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“…4; Righi et al 2010, Mizutani et al 2012, Lambertini et al 2013, Kanakis et al 2015, Herrera-Martinez et al 2017. SST expression may help to differentiate normal and tumor tissue in lung carcinoids and GEP-NENs and has been related to vascular/nerve invasion and metastasis (Herrera-Martinez et al 2017. The tumor SST expression profile may also be helpful for predicting treatment response (Reubi et al 2010, especially in aggressive cases ).…”

Section: Figurementioning

confidence: 99%

“…Unfortunately, results are based on retrospective heterogeneous cohorts, which may limit the reproducibility. Additionally, in some of the above indicated studies, SST expression by qPCR was determined in formalin-fixed paraffin embedded tumors, which may affect the expression profile in some samples (Sampedro-Nunez et al 2016, Herrera-Martinez et al 2017.…”

Section: Figurementioning

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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The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features

Cited by 15 publications

References 68 publications

Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in Gastroenteropancreatic Neuroendocrine Tumors

Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Novel Potential Biomarker in Gastroenteropancreatic Neuroendocrine Tumors

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

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

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