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探索TPX2在胰腺癌中的临床意义:从生物标志物到免疫治疗

Exploring the clinical significance of TPX2 in pancreatic cancer: from biomarker to immunotherapy.

作者信息

Zhang Zhengguang, Liu Zixian, Yao Ying, Li Min, Shen Cunsi, Zhou Fuqiong

机构信息

Central Laboratory, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.

School of Medicine, Nanjing University of Chinese Medicine, Jiangsu, Nanjing, China.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun;398(6):6843-6864. doi: 10.1007/s00210-024-03628-0. Epub 2024 Dec 17.

Abstract

Pancreatic cancer (PC) is a highly aggressive malignancy characterized by a dismal prognosis. The present study is designed to elucidate the pivotal role of Xenopus kinesin-like protein 2 (TPX2) as a biomarker with substantial clinical prognostic significance in PC. By conducting a comprehensive analysis of RNA sequencing data and protein expression profiles obtained from multiple databases, we observed a pronounced upregulation of TPX2 expression in PC tissues compared to normal pancreatic tissues. Importantly, TPX2 emerged as an independent prognostic factor, demonstrating remarkable diagnostic accuracy. Notably, its expression levels were found to be significantly associated with the PC immune microenvironment and sensitivity to various therapeutic modalities. Functional assays revealed that the silencing of TPX2 markedly inhibited PC cell proliferation, metastasis, and the growth of subcutaneous tumors in PC mouse models. These effects were potentially mediated by the activation of CD8 T cell immune responses and the inhibition of cell cycle progression and adhesion mechanisms. Taken together, our findings indicate that TPX2 may serve as a critical biomarker for the diagnosis and clinical management of patients with PC.

摘要

胰腺癌(PC)是一种具有高度侵袭性的恶性肿瘤,预后较差。本研究旨在阐明非洲爪蟾驱动蛋白样蛋白2(TPX2)作为一种在胰腺癌中具有重要临床预后意义的生物标志物的关键作用。通过对从多个数据库获得的RNA测序数据和蛋白质表达谱进行综合分析,我们观察到与正常胰腺组织相比,胰腺癌组织中TPX2的表达明显上调。重要的是,TPX2成为一个独立的预后因素,显示出显著的诊断准确性。值得注意的是,发现其表达水平与胰腺癌免疫微环境以及对各种治疗方式的敏感性显著相关。功能分析表明,在胰腺癌小鼠模型中,TPX2的沉默显著抑制了胰腺癌细胞的增殖、转移以及皮下肿瘤的生长。这些作用可能是通过激活CD8 T细胞免疫反应以及抑制细胞周期进程和黏附机制介导的。综上所述,我们的研究结果表明,TPX2可能作为胰腺癌患者诊断和临床管理的关键生物标志物。

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