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生长激素释放肽作为一种预后生物标志物,与胃癌前病变的免疫浸润和进展相关。

GHRL as a prognostic biomarker correlated with immune infiltrates and progression of precancerous lesions in gastric cancer.

作者信息

Wang Jinyun, Liu Dingwei, Xie Yong

机构信息

Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

出版信息

Front Oncol. 2023 Jul 4;13:1142017. doi: 10.3389/fonc.2023.1142017. eCollection 2023.

DOI:10.3389/fonc.2023.1142017
PMID:37469414
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10353738/
Abstract

OBJECTIVE

Ghrelin is a protein that regulate appetite and energy balance in the human body, which is encoded by the ghrelin prepropeptide gene (GHRL). GHRL is linked with carcinogenesis and immune regulation. However, the correlation of GHRL to prognosis and tumor-infiltrating lymphocytes in gastric cancer (GC) remains unclear.

METHODS

In this study, we assessed the transcriptional expression, prognosis, and different clinicopathological features about GHRL and the correlation between GHRL and tumor infiltration immune cells in GC patients based on the data published in the following databases: TIMER, GEPIA, GEO, STRING, UALCAN, TISIDB, and Kaplan-Meier Plotter. Furthermore, R software analysis for GC Correa' cascade was also provided. Finally, GHRL expression in GC tissues was assayed using quantitative real-time polymerase chain reaction and immunohistochemistry.

RESULTS

We found that GHRL expression in GC samples was lower than in normal samples and verified by quantitative PCR (qPCR) and immunohistochemistry. However, sample type, cancer stage, and worse survival were correlated to high GHRL expression. We also found that the expression of GHRL in dysplasia was significantly lower than that in CNAG and in GC. High GHRL expression was connected with immunomodulators, chemokines, and infiltrating levels of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in GC.

CONCLUSIONS

GHRL is a prognostic biomarker for GC patients, and it is correlated with progression of precancerous lesions in GC. It might lead to poor prognosis by regulating tumor immune microenvironment. Studies are important to explore therapeutic targeting GHRL in the future.

摘要

目的

胃饥饿素是一种调节人体食欲和能量平衡的蛋白质,由胃饥饿素前体肽基因(GHRL)编码。GHRL与肿瘤发生和免疫调节有关。然而,GHRL与胃癌(GC)预后及肿瘤浸润淋巴细胞之间的相关性仍不清楚。

方法

在本研究中,我们基于以下数据库发布的数据,评估了GC患者中GHRL的转录表达、预后及不同临床病理特征,以及GHRL与肿瘤浸润免疫细胞之间的相关性:TIMER、GEPIA、GEO、STRING、UALCAN、TISIDB和Kaplan-Meier Plotter。此外,还提供了对GC Correa级联反应的R软件分析。最后,采用定量实时聚合酶链反应和免疫组织化学法检测GC组织中GHRL的表达。

结果

我们发现GC样本中GHRL的表达低于正常样本,并通过定量PCR(qPCR)和免疫组织化学得到验证。然而,样本类型、癌症分期及较差的生存率与高GHRL表达相关。我们还发现,发育异常中GHRL的表达明显低于CNAG和GC中的表达。高GHRL表达与GC中的免疫调节剂、趋化因子以及B细胞、CD8 + T细胞、CD4 + T细胞、巨噬细胞、中性粒细胞和树突状细胞的浸润水平相关。

结论

GHRL是GC患者的预后生物标志物,且与GC癌前病变的进展相关。它可能通过调节肿瘤免疫微环境导致预后不良。未来探索靶向GHRL的治疗方法的研究具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/aeb46c39a27d/fonc-13-1142017-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/c9eb3e34d07c/fonc-13-1142017-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/0091a48d2ac4/fonc-13-1142017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/650611a2db9b/fonc-13-1142017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/c3e9a3d883db/fonc-13-1142017-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/aeb46c39a27d/fonc-13-1142017-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/c9eb3e34d07c/fonc-13-1142017-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/62e5fca53c77/fonc-13-1142017-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/21a34327115a/fonc-13-1142017-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/a33a12828966/fonc-13-1142017-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/6c886d8bf69b/fonc-13-1142017-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/0091a48d2ac4/fonc-13-1142017-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/650611a2db9b/fonc-13-1142017-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/c3e9a3d883db/fonc-13-1142017-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b0e/10353738/aeb46c39a27d/fonc-13-1142017-g009.jpg

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