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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Monday, April 15, 2024
Protein lactylation is a newly discovered posttranslational modification of proteins found in numerous human tissues. Although histone lactylation has been shown to play a crucial role in tumor proliferation, the role of lactylation-related genes in breast cancer and their association with the tumor microenvironment is not well understood. In a recent article published in Heliyon, researchers reported their findings after assessing the expression profiles of 22 lactylation-related genes in patients with breast cancer. Juliang Zhang, MD, of the Xijing Hospital, Air Force Military Medical University, Xi’an, Shaanxi, China, and colleagues identified two distinct lactylation clusters and identified specific gene clusters for breast cancer survival prognosis.
“Exploration of lactylation and its potential functions, as well as constructing a predictive model, can lead to novel diagnostic and therapeutic strategies for breast cancer,” stated Dr. Zhang and colleagues.
Gene-expression profiles and clinical data were compiled from 327 breast cancer tissues using data from the Gene Expression Omnibus (GEO) data portal (GSE20685). Data from the Cancer Genome Atlas (TCGA) database were also used in this study. Authors then analyzed the expression patterns of the lactylation-related genes and conducted unsupervised clustering to identify two lactylation clusters. A lactylation-related gene signature was developed and validated using the training and validation cohorts. Additionally, authors investigated immune cell infiltration and drug responses and used Cox analyses to assess the prognostic value of specific gene clusters.
Genetic data were separated based on specific patterns into two clusters: A and B. A total of 290 lactylation cluster–related differentially expressed genes were identified when the distinct biologic behaviors of each cluster were analyzed. Tumor microenvironment analyses revealed cluster B was significantly enriched in various pathways and processes, including progesterone-mediated oocyte maturation, cell cycle, and oocyte meiosis; the expression of most genes in cluster B related to immune checkpoints. Highly expressed in cluster A were CD44, NRP1, and TNFRSF14. A total of 153 genes were found to have significant prognostic value (P < .05), with patients belonging to gene subtype B had the most favorable overall survival compared with gene subtype A (P < .001).
Disclosure: The study authors reported no conflicts of interest.
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