Transcriptional splice variants of CD40 and its prognostic value in breast cancer

Authors: NEŞE ÜNVER, DİĞDEM YÖYEN ERMİŞ, BAHAR ZEHRA WEBER, GÜNEŞ ESENDAĞLI

Abstract: CD40 is an important tumor necrosis factor receptor (TNFR) family protein for the development of antitumor response against cancer cells, apart from its role in the regulation of the immune system as a costimulatory molecule. It is broadly expressed on the surface of immune cells and in diverse cancer types, including breast cancer. Here, we analyzed both CD40/CD40 ligand expression in breast cancer cells and tissues using public data sets and overall survival analysis in ungrouped breast cancer patients, as well as in the triple-negative breast cancer subtype. We detected CD40 gene expression along with its 3 different splice variants (variants 1-3), predominantly in the triple-negative subgroup of breast cancer cell lines. The results of the overall survival analysis showed that high CD40 gene expression, particularly in the triple-negative subgroup of breast cancer patients, is associated with better survival. In addition to the transcriptional levels of CD40 splice variants, investigation of protein levels of these variants will allow the categorization of breast cancer cells and reveal their potential as an immunotherapeutic target.

Keywords: CD40, breast cancer, alternative splicing, transcriptional variant, antitumor response

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