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嗜铬粒蛋白原A2(SCG2)和羧肽酶E(CPE)可能是用于识别胰腺神经内分泌肿瘤和实性假乳头状肿瘤的新型标志物。

SCG2 and CPE may be novel markers for the identification of pancreatic neuroendocrine tumors and solid pseudopapillary neoplasms.

作者信息

Yang Wuhan, Wang Shubin, Zhang Zhilei, Guo Hao, Liu Chengyu, Zhao Meng, Liu Yueping, Peng Li

机构信息

Department of Hepatobiliary Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

Department of General Medicine, the Fourth Hospital of Hebei Medical University, Shijiazhuang, China.

出版信息

Transl Cancer Res. 2024 Jul 31;13(7):3407-3417. doi: 10.21037/tcr-24-229. Epub 2024 Jul 18.

Abstract

BACKGROUND

Distinguishing pancreatic neuroendocrine tumors (pNETs) from solid pseudopapillary neoplasms (SPNs) is challenging, primarily due to their overlapping pathological characteristics. To address this, our study aims to identify and validate novel biomarkers that effectively differentiate between these two conditions. We focus on the exploration of new immunohistochemical markers to enhance this distinction.

METHODS

In this study, we analyzed genetic variations in pNETs and SPNs using the GSE43795 dataset from the Gene Expression Omnibus (GEO) database. Our approach was to identify genes with higher expression in pNETs compared to SPNs and normal pancreatic tissues. We conducted enrichment analyses to understand the functions of these genes. Furthermore, protein-protein interaction (PPI) network analysis was utilized to identify key genes associated with pNETs. Our sample consisted of 163 pancreatic tumor specimens, comprising 78 pNETs and 85 SPNs. We also collected clinicopathological data and used immunohistochemistry to measure the expression levels of these key genes.

RESULTS

The enrichment analysis revealed that genes overexpressed in pNETs were mainly involved in signal release, vesicle transport, and ion pathway activation, playing significant roles in endocrine processes like insulin secretion, dopamine synapses, and circadian rhythm regulation. The PPI analysis identified secretogranin II (SCG2), carboxypeptidase E (CPE), and chromogranin A (CgA, CHGA) as key markers for differentiating pNETs from SPNs. Immunohistochemical validation of these markers demonstrated high sensitivity (SCG2: 98.7%, CPE: 97.4%) and specificity (100%), indicating their superior discriminative power compared to traditional markers like CgA, β-catenin, lymphoid enhancer-binding factor 1 (LEF1), and vimentin.

CONCLUSIONS

Our study indicates that SCG2 and CPE are effective, novel immunohistochemical biomarkers for differentiating pNETs from SPNs.

摘要

背景

区分胰腺神经内分泌肿瘤(pNETs)与实性假乳头状肿瘤(SPNs)具有挑战性,主要是因为它们的病理特征存在重叠。为解决这一问题,我们的研究旨在识别和验证能够有效区分这两种病症的新型生物标志物。我们专注于探索新的免疫组化标志物以加强这种区分。

方法

在本研究中,我们使用来自基因表达综合数据库(GEO)的GSE43795数据集分析了pNETs和SPNs中的基因变异。我们的方法是识别与SPNs和正常胰腺组织相比,在pNETs中表达更高的基因。我们进行了富集分析以了解这些基因的功能。此外,利用蛋白质-蛋白质相互作用(PPI)网络分析来识别与pNETs相关的关键基因。我们的样本包括163个胰腺肿瘤标本,其中78个为pNETs,85个为SPNs。我们还收集了临床病理数据,并使用免疫组化来测量这些关键基因的表达水平。

结果

富集分析显示,在pNETs中过表达的基因主要参与信号释放、囊泡运输和离子途径激活,在胰岛素分泌、多巴胺突触和昼夜节律调节等内分泌过程中发挥重要作用。PPI分析确定分泌粒蛋白II(SCG2)、羧肽酶E(CPE)和嗜铬粒蛋白A(CgA,CHGA)为区分pNETs与SPNs的关键标志物。这些标志物的免疫组化验证显示出高敏感性(SCG2:98.7%,CPE:97.4%)和特异性(100%),表明它们与CgA、β-连环蛋白、淋巴样增强因子1(LEF1)和波形蛋白等传统标志物相比具有更强的鉴别能力。

结论

我们的研究表明,SCG2和CPE是区分pNETs与SPNs的有效新型免疫组化生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec99/11319939/065bad9d31cb/tcr-13-07-3407-f1.jpg

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