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

生长素释放肽-O-酰基转移酶 (GOAT) 酶作为胃肠胰神经内分泌肿瘤的新型潜在生物标志物

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作者:Aura D Herrera-Martínez, Manuel D Gahete, Rafael Sánchez-Sánchez, Emilia Alors-Perez, Sergio Pedraza-Arevalo, Raquel Serrano-Blanch, Antonio J Martínez-Fuentes, Maria A Gálvez-Moreno, Justo P Castaño, Raúl M Luque7

Conclusions

These 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.

Methods

Here, 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.

Results

The 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. Conclusions: These 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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