ABSTRACT
The aim of this study was to evaluate the prognostic value of light chain 3 (LC3) expression in triple-negative breast cancer (TNBC) and describe the association of LC3 expression with the occurrence of metastasis. LC3 expression in tissue microarray was evaluated by immunohistochemistry in 163 patients with TNBC. The prognostic value of LC3 expression was assessed by a Cox regression model adjusted for clinical characteristics. Low LC3 expression in TNBC was observed in 56 (34.4 %) of 163 TNBC. Low LC3 expression significantly correlated with a higher risk of distant metastasis, rather than locoregional relapse. The 10-year distant metastases-free survival for LC3-negative and LC3-positive patients was 57.2 and 95.1 %, respectively (p < 0.0001). Accordingly, a significant correlation was found between LC3 expression and disease-free survival (DFS) and overall survival (OS). Multivariate analysis indicated that LC3 negative was a significant independent prognostic factor of DFS (p = 0.019), but not for OS (p = 0.545) in all patients. Our results suggested that expression of LC3 in TNBC was associated with higher distant metastases. This finding could open new avenues for the development of novel therapy strategies to TNBC.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Microtubule-Associated Proteins/biosynthesis , Adult , Aged , Disease-Free Survival , Female , Humans , Immunohistochemistry , Microtubule-Associated Proteins/analysis , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Tissue Array Analysis , Young AdultABSTRACT
BACKGROUND: Beclin 1 is a main actor of autophagy. The expression of Beclin 1 and its prognostic role in gastric cancer is largely unexplored. The purpose of the present study is to investigate the expression of beclin 1 in gastric cancer cells, tissues and its relationship with prognosis. METHODS: The expression of Beclin 1 was detected in 271 specimens of lymph-node positive gastric cancer patients by immunohistochemistry. The correlation of Beclin 1 expression to clinicopathologic features and survival of gastric cancer was studied. Beclin-1 expression in gastric cancer cell lines and clinical specimens is also detected using reverse transcription-PCR and Western blotting. RESULTS: Beclin 1 is up-regulated at both mRNA and protein levels in six gastric cancer cell lines compared with those in normal gastric mucosa cell line (GES-1). The expression of Beclin-1 in gastric clinical specimens is also higher than those in the adjacent noncancerous tissues. Of the 271 patients, 229 (84.5%) were Beclin 1 high expression tumors by immunohistochemistry. Beclin 1 expression is closely associated with intravascular embolus. Kaplan-Meier analysis showed high beclin 1 expression was associated with longer overall survival. Both univariate analysis and multivariate analysis revealed that Beclin 1 expression were independent prognostic factors in the patients with node-positive gastric cancer. CONCLUSIONS: Our findings strongly suggest that Beclin 1 has a potential role in tumorigenesis of gastric cancer and could be a promising biomarker for predicting the prognosis of patients with lymph node-positive gastric cancer. It might also serve as a novel therapeutic target for gastric cancer treatment.
