AI Article Synopsis

  • Pancreatic cancer (PC) has a high mortality rate and poor prognosis despite treatment advances, highlighting the need for effective biomarkers.
  • This study used bioinformatic analyses to identify the histone lysine demethylases (KDMs) as potential therapeutic targets, finding that higher levels of KDM1A, KDM5A, and KDM5B correlated with improved patient survival.
  • Additionally, these KDMs were linked to immune cell infiltration and various cellular pathways, indicating their potential as biomarkers and targets for developing new treatment strategies against this aggressive disease.

Article Abstract

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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11373554PMC
http://dx.doi.org/10.7150/ijms.96134DOI Listing

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Article Synopsis
  • Pancreatic cancer (PC) has a high mortality rate and poor prognosis despite treatment advances, highlighting the need for effective biomarkers.
  • This study used bioinformatic analyses to identify the histone lysine demethylases (KDMs) as potential therapeutic targets, finding that higher levels of KDM1A, KDM5A, and KDM5B correlated with improved patient survival.
  • Additionally, these KDMs were linked to immune cell infiltration and various cellular pathways, indicating their potential as biomarkers and targets for developing new treatment strategies against this aggressive disease.
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The catalytic domains of all human KDM5 JmjC demethylases catalyse N-methyl arginine demethylation.

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  • Jumonji-C lysine demethylases (JmjC-KDMs) are known for demethylating N-methyllysine residues on histones, but some also exhibit N-methylarginine demethylase (RDM) activity.
  • Biochemical screening showed that human KDM5s (KDM5A-D) and KDM4E have both KDM and RDM activities, while KDM4A/D show less RDM capability, and KDM1A exhibits no RDM activity.
  • The study suggests that JmjC-KDMs might have broader catalytic functions beyond just demethylation of N-methyllysine, paving the way for future research into their biological roles.
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