Promoter's hypermethylation and down-regulated expression of amphiregulin in breast carcinoma: a potential prognostic marker

To evaluate the role of amphiregulin (AREG), a ligand of epidermal growth factor receptor, in breast invasive carcinoma (BRIC) the present study was initiated. For this purpose, we used freely available GeneCards Suite for AREG enrichment analysis, the online UALCAN web portal for analysis of differential expression and promoter’s methylation status of AREG, the online cBioPortal cancer genome atlas to document carcinoma-associated AREG mutations and CCLE (Cancer Cell Line Encyclopedia) and GDSC (Genomics of Drug Sensitivity in Cancer) toolkit to document AREG’s sensitivity towards various anti-cancer drugs. We observed lower expression of AREG in the majority of patients, in comparison to normal controls, due to promoter’s hypermethylation. While AREG’s upregulation was examined in premenopausal condition, stage 1 and a few other patient groups. The reduced expression of AREG in human epidermal growth factor receptor 2 (HER2) positive, triple-negative and patients of many other subtypes highlights the relevance of AREG with the progression of the disease. Moreover, the AREG’s expression improved the effectiveness of anti-neoplastic drugs but confers resistance against gamma-secretase inhibitors. Patients exhibiting lower/medium levels of AREG’s expression had better survival chances. In the future, an investigation of the factors which modulate methylation patterns of AREG’s promoter and an evaluation of the prognostic power of AREG’s expression will facilitate the identification of novel therapeutic channels for better prognosis of BRIC and devise a multilayered treatment strategy.

Amphiregulin (AREG); Invasive lobular carcinoma (ILC); Triple-negative breast carcinoma (TNBC); Gene expression; Promoter methylation; Survival analysis

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