Decreased BECN1 mRNA Expression in Human Breast Cancer is Associated With Estrogen Receptor-Negative Subtypes and Poor Prognosis
Hao Tang,
Salwa Sebti,
Rossella Titone,
Yunyun Zhou,
Ciro Isidoro,
Theodora S. Ross,
Hanina Hibshoosh,
Guanghua Xiao,
Milton Packer,
Yang Xie,
Beth Levine
Affiliations
Hao Tang
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Salwa Sebti
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Rossella Titone
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Yunyun Zhou
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Ciro Isidoro
Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del Piemonte Orientale “A Avogrado”, Via Solaroli 17, 28100 Novara, Italy
Theodora S. Ross
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Hanina Hibshoosh
Department of Pathology and Cell Biology, Columbia University College of Physicians & Surgeons, New York, NY 10032, United States
Guanghua Xiao
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Milton Packer
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Yang Xie
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Beth Levine
Center for Autophagy Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States
Both BRCA1 and Beclin 1 (BECN1) are tumor suppressor genes, which are in close proximity on the human chromosome 17q21 breast cancer tumor susceptibility locus and are often concurrently deleted. However, their importance in sporadic human breast cancer is not known. To interrogate the effects of BECN1 and BRCA1 in breast cancer, we studied their mRNA expression patterns in breast cancer patients from two large datasets: The Cancer Genome Atlas (TCGA) (n = 1067) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1992). In both datasets, low expression of BECN1 was more common in HER2-enriched and basal-like (mostly triple-negative) breast cancers compared to luminal A/B intrinsic tumor subtypes, and was also strongly associated with TP53 mutations and advanced tumor grade. In contrast, there was no significant association between low BRCA1 expression and HER2-enriched or basal-like subtypes, TP53 mutations or tumor grade. In addition, low expression of BECN1 (but not low BRCA1) was associated with poor prognosis, and BECN1 (but not BRCA1) expression was an independent predictor of survival. These findings suggest that decreased mRNA expression of the autophagy gene BECN1 may contribute to the pathogenesis and progression of HER2-enriched, basal-like, and TP53 mutant breast cancers.
