Prevalence and Significance of AGR2 Expression in Human Cancer

IF 2.9 2区医学 Q2 ONCOLOGY Cancer Medicine Pub Date : 2024-11-12 DOI:10.1002/cam4.70407

Nina Schraps, Jacob Constantin Port, Anne Menz, Florian Viehweger, Seyma Büyücek, David Dum, Ria Schlichter, Andrea Hinsch, Christoph Fraune, Christian Bernreuther, Martina Kluth, Claudia Hube-Magg, Katharina Möller, Viktor Reiswich, Andreas M. Luebke, Patrick Lebok, Sören Weidemann, Guido Sauter, Maximilian Lennartz, Frank Jacobsen, Till S. Clauditz, Andreas H. Marx, Ronald Simon, Stefan Steurer, Baris Mercanoglu, Nathaniel Melling, Thilo Hackert, Eike Burandt, Natalia Gorbokon, Sarah Minner, Till Krech, Florian Lutz

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Abstract

Backround

Anterior gradient 2 (AGR2) is a resident endoplasmic reticulum (ER) protein with a vital role in embryonal development, mucus maturation, tissue regeneration, and wound healing.

Methods

To determine the prevalence and clinical significance of AGR2 expression in cancer, a tissue microarray containing 14,966 tumors from 134 different tumor types and subtypes as well as 608 samples of 76 different normal tissue types was analyzed by immunohistochemistry (IHC).

Results

AGR2 positivity was found in 103 of 134 tumor categories, and 83 tumor categories contained at least one strongly positive case. AGR2 expression was most frequently seen in tumors of the female genital tract, particularly adenocarcinomas (up to 100%), various breast cancer subtypes (57.1%–100%), urothelial carcinoma (74.6%–100%), adenocarcinomas of the upper and lower gastrointestinal tract (93.6%–99.6%), and pancreaticobiliary cancers (65.2%–98.2%). AGR2 positivity was slightly less common in squamous cell carcinomas (46.4%–77.3%) and mainly absent in mesenchymal and lymphoid tumors. While AGR2 expression was only weak or absent in the normal thyroid, it was moderate to strong in 46.0% of adenomas, 52.8% of follicular carcinomas, and 81.8% of papillary carcinomas of the thyroid. High AGR2 expression was strongly linked to poor ISUP (p < 0.0001), Fuhrman (p < 0.0001), and Thoenes (p < 0.0001) grades as well as advanced pT stage (p = 0.0035) in clear cell renal cell carcinoma (ccRCC). Low AGR2 expression was associated with high BRE grade in breast cancer (p = 0.0049), nodal metastasis (p = 0.0275) and RAS mutation (p = 0.0136) in colorectal cancer, nodal metastasis (p = 0.0482) in endometrioid endometrial carcinoma, high grade in noninvasive urothelial carcinoma (p = 0.0003), and invasive tumor growth in urothelial carcinoma (p < 0.0001).

Conclusions

It is concluded that AGR2 expression occurs in a broad range of different tumor entities and that AGR2 assessment may serve as a diagnostic aid for the distinction of thyroidal neoplasms and as a prognostic marker in various cancer types.

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人类癌症中 AGR2 表达的普遍性和重要性。

背景：前梯度2（AGR2）是一种常驻内质网（ER）蛋白，在胚胎发育、粘液成熟、组织再生和伤口愈合中发挥着重要作用：为了确定 AGR2 在癌症中的表达率和临床意义，我们用免疫组化（IHC）方法分析了包含 134 种不同肿瘤类型和亚型的 14,966 个肿瘤以及 76 种不同正常组织类型的 608 个样本的组织芯片：结果：134种肿瘤中有103种发现AGR2阳性，83种肿瘤至少有一种呈强阳性。AGR2最常见于女性生殖道肿瘤，尤其是腺癌（高达100%）、各种乳腺癌亚型（57.1%-100%）、尿路上皮癌（74.6%-100%）、上下消化道腺癌（93.6%-99.6%）和胰胆管癌（65.2%-98.2%）。AGR2 阳性在鳞状细胞癌（46.4%-77.3%）中略少见，在间质和淋巴肿瘤中主要缺乏。虽然AGR2在正常甲状腺中仅有微弱表达或无表达，但在46.0%的腺瘤、52.8%的滤泡癌和81.8%的甲状腺乳头状癌中却有中度到高度表达。AGR2的高表达与ISUP差密切相关（p 结论：AGR2的高表达与ISUP差密切相关：结论：AGR2的表达广泛存在于不同的肿瘤实体中，AGR2评估可作为区分甲状腺肿瘤的诊断辅助手段，也可作为各种癌症类型的预后标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.