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Differential expression of gasdermin family of proteins between triple-negative breast cancer (TNBC) and non-TNBC, and based on ER, PR and HER2 status.
  • Caglar BERKEL
Caglar BERKEL
Tokat Gaziosmanpasa Universitesi Fen Edebiyat Fakultesi

Corresponding Author:[email protected]

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Abstract

Breast cancer is the most common malignancy in women worldwide, with incidence expected to increase by more than 46% by 2040. Breast cancer is classified into various subtypes based on the status of estrogen receptor (ER), progesterone receptor (PR) and HER2 (ERBB2). These subtypes have huge differences in both treatment and prognosis. TNBC (triple-negative breast cancer) is the most lethal among breast cancer subtypes. Pyroptosis is a programmed pro-inflammatory cell death mechanism leading to the formation of membrane pores mediated by gasdermin (GSDM) proteins. I first explored how the transcript levels of gasdermin family of genes (GSDMA-E and PJVK) differ between TNBC and non-TNBC. I found that the expression of GSDMC and GSDME is increased; but, the expression of GSDMD is decreased in TNBC compared with non-TNBC. I further investigated ER-, PR-, and HER2-dependent changes in the expression of GSDMC, GSDMD and GSMDE. I observed decreased GSDMC mRNA expression in breast tumors with ER-positive and PR-positive status than in those with ER-negative and PR-negative status, respectively. In contrast, HER2-positive breast tumors have higher expression of GSDMC compared to HER2-negative breast tumors. Unlike GSDMC, the expression of GSDMD was higher in ER-positive and PR-positive breast cancer samples than in ER-negative and PR-negative samples, respectively. I found that GSDME expression is lower in ER-positive breast tumors compared to ER-negative breast tumors. Lastly, I showed that breast tumors from premenopausal women have slightly higher transcript levels of GSDME than breast tumors from postmenopausal women. Combined, this study points to the possible differences in pyroptotic cell death between TNBC and non-TNBC, and also between different breast cancer subgroups based on receptor status (ER, PR or HER2).