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William J. Gradishar, MD, FACP, FASCO
William J. Gradishar, MD, FACP, FASCO
Posted: Friday, April 12, 2024
For patients with estrogen receptor (ER)-positive breast cancer, the central molecular switch DARPP-32 may significantly impact their prognosis, according to a study presented at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract LB009/9). Given the potential role of this protein as a therapeutic target to improve clinical outcomes in this patient population, additional investigative efforts focused on elucidating the complex mechanisms of breast cancer progression are warranted, explained Behnaz Saidy, PhD, of the University of Nottingham, United Kingdom, and colleagues.
The study employed a DARPP-32 knockdown model to identify 202 differentially expressed transcripts in ER-positive breast cancer cells. Cells were treated with either 17β-estradiol or protein kinase A inhibitor fragment amides. After treatment, the differential expression was reduced to 193 and 181 transcripts, respectively. Using an Artificial Neural Network (ANN) approach, the investigators compared genes associated with the expression of DARRP-32 with the differentially expressed transcripts in 1,980 patients with ER-positive breast cancer recruited from the METABRIC cohort.
The study authors reported several genetic overlaps with genes found in cell line transcriptomics, including PTK7, KLK6, and TRAF5. In addition, a significant association was revealed between the phosphorylation levels of DARPP-32 threonine-34 in patients using ANN and the expression of the DKK1 and GRB7 genes. Based on these findings, an ANN-based integrative data mining approach was employed to identify the interactions between different genes, resulting in the development of an interactome map. By using the interactome map, the researchers have identified 2,144 and 1,003 genes in patients with ER-positive and ER-negative breast cancer, respectively.
Disclosure: The study authors reported no conflicts of interest.
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