Abstract
BackgroundThe major pathological type of non-small cell lung cancer is lung adenocarcinoma (LAC), which has a poor prognosis. BRCA1-associated protein-1 (BAP1) is a newly identified tumor suppressor that regulates a number of cellular functions in somatic malignancies. However, the impact of BAP1 expression in LAC has not been investigated.MethodsA total of 112 cases of LAC and 101 cases of non-neoplastic lung diseases were included in this study. The study focused on BAP1 expression in lung tissues and its relationship to patients’ clinical and pathological features. BAP1 expression was detected by immunohistochemistry. A human LAC cell line NCI-H1299 was transfected with lipofectamine p3xFLAG-BAP1. BAP1 gene expression was silenced in another LAC cell line NCI-H1650, in order to test the inhibitory effect of BAP1 on cell migration and invasion, as well as cell cycle regulation.ResultsBAP1 expression showed a negative correlation with tumorigenesis of LAC (p <0.001) and lymph node metastasis (p = 0.010). High expression of BAP1 predicted longer disease free survival (p = 0.040) and overall survival (p = 0.021) of LAC patients. In functional assays, BAP1 was found to inhibit the migration and invasion of LAC cells, and promoted their apoptosis and necrosis.ConclusionsWe identify BAP1 as a LAC precursor as well as a robust prognostic indicator in LAC patients. This study provides in vitro rationale for the further investigation of BAP1 in preclinical studies.
Highlights
The major pathological type of non-small cell lung cancer is lung adenocarcinoma (LAC), which has a poor prognosis
breast cancer 1 (BRCA1)-associated protein-1 (BAP1) expression in lung adenocarcinoma and clinicopathologic findings To investigate the potential role of BAP1 in the generation and progression of LAC, we performed immunohistochemical staining on samples from 112 cases of LAC and 101 cases of non-neoplastic lung diseases
We conducted a statistical analysis to explore the correlation between BAP1 expression and the clinicopathologic characteristic of LAC patients
Summary
The major pathological type of non-small cell lung cancer is lung adenocarcinoma (LAC), which has a poor prognosis. Lung adenocarcinoma (LAC) is currently the predominant histological subtype of NSCLC [2] with an average 5-year survival rate of 15 % despite using epidermal growth factor receptor (EGFR)-targeted therapies. This poor outcome is due in a large part to the delay in Ubiquitin proteasome system (UPS) is involved in intracellular protein degradation, playing a crucial role in physiological processes including cell proliferation, apoptosis and migration [6, 7]. Six subfamilies of DUBs have been found: the ubiquitin C-terminal hydrolases (UCHs), the ubiquitin-specific proteases (USPs/ UBPs), the ovarian tumor proteases (OTUs), the Machado-Joseph disease protein domain proteases (MJDs), the Jab1/MPN domain-associated metalloisopeptidase (JAMM) domain proteins and the monocyte chemotactic protein-induced protein (MCPIP) [9, 10]
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