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胃饥饿素-O-酰基转移酶（GOAT）酶作为胃肠胰神经内分泌肿瘤的一种新的潜在生物标志物。

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

机构信息

Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain.

Endocrinology and Nutrition Service, Reina Sofia University Hospital, Córdoba, Spain.

出版信息

Clin Transl Gastroenterol. 2018 Oct 8;9(10):196. doi: 10.1038/s41424-018-0058-8.

DOI:10.1038/s41424-018-0058-8
PMID:30297816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6175927/
Abstract

OBJECTIVES

The 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.

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.

摘要

目的

生长激素释放肽系统成分的存在及其改变与神经内分泌肿瘤（NETs）的发生和进展之间的关系仍存在争议，目前尚不清楚。

方法

在这里，我们系统地评估了胃肠胰神经内分泌肿瘤（GEP-NETs）中关键生长激素释放肽系统成分的表达水平（通过定量 PCR），并与非肿瘤相邻（NTA；n=42）和正常组织（NT；n=14）进行了比较。然后，我们分析了它们与临床组织学特征的潜在关联。

结果

结果表明，生长激素及其受体 GHSR1a 在很大一部分正常组织中存在，而生长激素释放肽-O-酰基转移酶（GOAT）和剪接变异体 In1-生长激素和 GHSR1b 则在正常组织中存在的比例较低。相比之下，所有生长激素释放肽系统成分在肿瘤和 NTA 组织中都存在很高的比例。与 NTA 相比，GOAT 在肿瘤样本中的表达（通过定量 PCR（qPCR））明显上调，而 ghrelin、In1-ghrelin 和 GHSR1a 则呈现上调趋势。此外，这些成分的表达与关键临床参数显示出显著的相关性。免疫组化进一步证实了 GOAT 在肿瘤样本中相对于 NTA 区域的明显过表达，表明该酶在胃肠道 NETs 中特别过表达，且与肿瘤直径直接相关。

结论

这些结果为生长激素释放肽系统成分在 GEP-NETs 中的存在及其潜在的病理生理意义提供了新的信息，其中 GOAT 可能代表一种新的诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/11d27a215ce1/41424_2018_58_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/f8cc60194879/41424_2018_58_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/d45d117cb0d4/41424_2018_58_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/3b47b7729e16/41424_2018_58_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/11d27a215ce1/41424_2018_58_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/f8cc60194879/41424_2018_58_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/d45d117cb0d4/41424_2018_58_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/3b47b7729e16/41424_2018_58_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77d7/6175927/11d27a215ce1/41424_2018_58_Fig4_HTML.jpg

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