Abstract
PurposeThe purpose of this study was to investigate the expression of autophagy-related proteins in relation to androgen receptor (AR) status in estrogen receptor (ER)-negative breast cancers.MethodsWe extracted 334 ER-negative breast cancer samples to construct tissue microarrays (TMAs), which were immunohistochemically stained for autophagy-related proteins (beclin-1, LC3A, LC3B, p62) and for AR and HER-2.ResultsThere were 127 AR-positive cases and 207 AR-negative cases, and 140 HER-2-positive cases and 194 HER-2 negative cases. The AR-negative group was associated with tumoral LC3A expression (P<0.001), while the AR-positive group was associated with tumoral BNIP3 expression (P<0.001). Tumoral LC3A was most highly expressed in the AR-negative and HER-2 negative group, while stromal LC3A showed the highest expression in the AR-negative and HER-2-positive group. Tumoral BNIP3 and stromal BNIP3 were highest in the AR-positive and HER-2-negative group. In the AR-positive and HER-2-negative group, stromal p62 positivity was an independent factor that was statistically significant in its association with shorter disease-free survival (DFS) (Hazard ratio: 10.21, 95% CI: 1.130–92.31, P = 0.039). Shorter DFS was associated with tumoral LC3A positivity (Hazard ratio: 10.28, 95% CI: 2.068–51.19, P = 0.004) in the AR-negative and HER-2-positive group.ConclusionIn ER-negative breast cancers, AR status was associated with expression of different types of autophagy-related proteins. Tumoral LC3A was most highly expressed in AR-negative breast cancers, while tumor BNIP3 was highest in AR-positive breast cancers.
Highlights
Autophagy is defined as the lysosomal degradation of cellular components within cells
Autophagyrelated proteins that are used as markers to evaluate activation levels of autophagy include: beclin-1 [5,6,7,8], a protein known to participate in the nucleation process; LC3A [9,10,11], a protein that participates in the elongation process and thereby forms autophagosomes; P62, a scaffolding protein that transfers ubiquitinated protein to autophagosomes; and BNIP3, which plays a central role in mitophagy, the autophagy process within mitochondria
When estrogen receptor (ER) negative cancer was divided into groups according to androgen receptor (AR) and HER-2 status, these groups exhibited a noticeable difference in age at diagnosis and Ki-67 expression levels
Summary
Autophagy is defined as the lysosomal degradation of cellular components within cells. Autophagy removes dysfunctional or damaged cellular components while recycling cellular components that can be re-used, thereby playing an important homeostatic role within the cell [1,2,3,4]. In highly aggressive malignant tumors, where stresses are higher for metabolic demand, these specialized metabolic pathways may not be sufficient, so some tumors may adopt an alternative metabolic pathway of autophagy [12,13]. In such cases, autophagy works to recycle cytoplasmic components to supply extra energy to the cell. The autophagy process should be closely associated with metabolism in cancer progression and survival
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