Nuclear Symmetric Dimethylarginine Staining is Indicative of Pancreatic Ductal Adenocarcinoma.

IF 1.7 4区医学 Q3 GASTROENTEROLOGY & HEPATOLOGY

Pancreas Pub Date : 2025-09-03 DOI:10.1097/MPA.0000000000002509

Kritisha Bhandari, Sheeja Aravindan, Chao Xu, Kar-Ming Fung, Wei-Qun Ding

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引用次数: 0

Abstract

Objective: The protein arginine methyltransferase 5 (PRMT5) is a type II PRMT that is responsible for the majority of symmetric dimethylarginine (SDMA) in eukaryotic cells. While PRMT5 is overexpressed in pancreatic ductal adenocarcinoma (PDAC), the SDMA expression patterns in PDAC tissues have not been examined. This study is aimed to characterize the SDMA expression patterns in PDAC cells and patient tissues.

Methods: Tissue microarray (TMA), immunohistochemistry (IHC) of PDAC cell lines and archival PDAC tissue blocks, and western blotting were applied to this study.

Results: Expression of PRMT5 and SDMA is elevated in PANC-1 and MIA PaCa-2 cells compared with that in the pancreatic ductal HPNE cell line. Pharmacological inhibition of PRMT5 reduces the SDMA level, indicating that PRMT5 is primarily responsible for SDMA in PDAC cells. IHC staining of the TMA containing 158 patient samples demonstrates that nuclear SDMA staining is significantly enhanced in PDAC tissues compared to normal and tumor adjacent tissues. The elevated SDMA level is evident in tissues from patients with early-stage PDAC, which is further verified using the archival PDAC tissue blocks. In addition, the SDMA staining is highly clustered in the Islets of Langerhans of the pancreas, irrespective of the disease states.

Conclusions: We demonstrate for the first time that nuclear SDMA staining is significantly enhanced in PDAC tissues and in the Islets of Langerhans of the pancreas, indicating novel tissue IHC markers for PDAC and the endocrine units of the pancreas.

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核对称二甲基精氨酸染色提示胰腺导管腺癌。

目的：蛋白精氨酸甲基转移酶5 （PRMT5）是一种II型PRMT，负责真核细胞中大部分对称二甲基精氨酸（SDMA）的产生。虽然PRMT5在胰腺导管腺癌（PDAC）中过表达，但SDMA在PDAC组织中的表达模式尚未被研究。本研究旨在表征SDMA在PDAC细胞和患者组织中的表达模式。方法：采用组织芯片（TMA）、PDAC细胞株免疫组化（IHC）、PDAC档案组织块免疫印迹（western blotting）技术进行研究。结果：PANC-1和MIA PaCa-2细胞中PRMT5和SDMA的表达高于胰腺导管HPNE细胞系。药物抑制PRMT5可降低SDMA水平，表明PRMT5在PDAC细胞中主要负责SDMA。158例患者TMA的免疫组化染色显示，与正常组织和肿瘤邻近组织相比，PDAC组织的核SDMA染色明显增强。在早期PDAC患者的组织中，SDMA水平明显升高，这一点通过档案PDAC组织块得到进一步证实。此外，无论疾病状态如何，SDMA染色高度聚集在胰腺的朗格汉斯岛。结论：我们首次证明核SDMA染色在PDAC组织和胰腺朗格汉斯胰岛中显著增强，表明PDAC和胰腺内分泌单位的新组织IHC标记。

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

Pancreas 医学-胃肠肝病学

CiteScore

4.70

自引率

3.40%

发文量

289

审稿时长

1 months

期刊介绍： Pancreas provides a central forum for communication of original works involving both basic and clinical research on the exocrine and endocrine pancreas and their interrelationships and consequences in disease states. This multidisciplinary, international journal covers the whole spectrum of basic sciences, etiology, prevention, pathophysiology, diagnosis, and surgical and medical management of pancreatic diseases, including cancer.