Decreased expression of autophagy protein LC3 and stemness (CD44+/CD24−/low) indicate poor prognosis in triple-negative breast cancer

Abstract

This study evaluated the prognostic value of expression of autophagy protein light chain 3 (LC3) and the prognostic value of coexpression of LC3 and stemness markers CD44+/CD24-/low in triple-negative breast cancer (TNBC). LC3 and LC3/CD44+/CD24-/low immunophenotypes in tumor tissues were evaluated by immunohistochemistry in 67 TNBC patients. LC3- was expressed in 30 (44.78%) cases. The LC3- phenotype revealed a significant negative association with overall survival in both univariate (P = .0006) and multivariate (P = .0153) analyses. LC3-/CD44+/CD24-/low phenotype was observed in 24 (35.82%) of 67 TNBC patients. According to Kaplan-Meier analysis, prognosis was significantly worse in tumors with LC3-/CD44+/CD24-/low phenotype (P = .0280). Multivariate analysis indicated that LC3-/CD44+/CD24-/low phenotype was a significant independent prognostic indicator of overall survival. These results suggest that LC3 suppresses TNBC in mature tumor cells and cancer stem cells (CSCs). In conclusion, this study suggests that CSCs are linked to progression of autophagy in TNBC. During the progression and development of TNBC, autophagy of CSCs/progenitor cells is low. LC3-/CD44+/CD24-/low immunophenotype indicates a highly aggressive TNBC subgroup associated with a poor prognosis. This study investigated that LC3 deficiency may restrain TNBC in mature tumor cells and CSCs. Therefore, a reasonable inference is that inducing autophagy may be an effective therapeutic strategy in TNBC.