多项综合分析发现赖氨酸去甲基化酶 KDM 是胰腺癌的潜在治疗靶点

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC ACS Applied Electronic Materials Pub Date : 2024-08-12 eCollection Date: 2024-01-01 DOI:10.7150/ijms.96134
Wan-Jou Shen, Hsuan-Min Kao, Chih-Yang Wang, Rubina Kousar, Jing-Shan Lin, Ching-Chung Ko, Hung-Yun Lin, Hoang Dang Khoa Ta, Gangga Anuraga, Do Thi Minh Xuan, Sachin Kumar, Sanskriti Dey, Ngoc Phung Ly, Wei-Jan Wang
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摘要

胰腺癌(PC)是一种具有挑战性的异质性疾病,死亡率很高。尽管治疗手段不断进步,但胰腺癌患者的预后仍然很差,疾病复发的几率很高。生物标志物对于诊断癌症、预测患者预后和选择治疗方法至关重要。然而,目前PC缺乏有效的生物标志物,这可能会导致现有治疗方法的不足。这些发现凸显了开发新型抗癌策略的迫切性。本研究利用多种全面的生物信息学分析来确定PC的潜在治疗靶基因,重点关注组蛋白赖氨酸去甲基化酶(KDMs)。我们发现,KDM家族基因,尤其是KDM1A、KDM5A和KDM5B的高表达水平与队列中总生存率的提高有关。此外,各种免疫细胞(包括 B 细胞、中性粒细胞、CD8+ T 细胞、树突状细胞和巨噬细胞)的浸润与 KDM1A、KDM5A 和 KDM5B 的表达呈正相关。此外,MetaCore通路分析显示了KDM1A与细胞周期和增殖之间、KDM5A与DNA损伤和通过同源重组进行双链断裂修复之间以及KDM5B与WNT/β-catenin信号转导之间的有趣联系。这些研究结果表明,KDM1A、KDM5A 和 KDM5B 可作为 PC 颇具前景的生物标记物和治疗靶点,PC 是一种非常重要的疾病,因为它具有侵袭性,而且迫切需要新型生物标记物来改善诊断和治疗。
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Multiple Comprehensive Analyses Identify Lysine Demethylase KDM as a Potential Therapeutic Target for Pancreatic Cancer.

Pancreatic cancer (PC) is a challenging and heterogeneous disease with a high mortality rate. Despite advancements in treatment, the prognosis for PC patients remains poor, with a high chance of disease recurrence. Biomarkers are crucial for diagnosing cancer, predicting patient prognosis and selecting treatments. However, the current lack of effective biomarkers for PC could contribute to the insufficiency of existing treatments. These findings underscore the urgent need to develop novel strategies to fight this disease. This study utilized multiple comprehensive bioinformatic analyses to identify potential therapeutic target genes in PC, focusing on histone lysine demethylases (KDMs). We found that high expression levels of KDM family genes, particularly KDM1A, KDM5A and KDM5B, were associated with improved overall survival in the cohort. Furthermore, the infiltration of various immune cells, including B cells, neutrophils, CD8+ T cells, dendritic cells, and macrophages, was positively correlated with KDM1A, KDM5A, and KDM5B expression. Moreover, MetaCore pathway analysis revealed interesting connections between KDM1A and the cell cycle and proliferation, between KDM5A and DNA damage and double-strand break repair through homologous recombination, and between KDM5B and WNT/β-catenin signaling. These findings suggest that KDM1A, KDM5A and KDM5B may serve as promising biomarkers and therapeutic targets for PC, a disease of high importance due to its aggressive nature and urgent need for novel biomarkers to improve diagnosis and treatment.

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