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BMC Cancer. 2016 Aug 23;16(1):670. doi: 10.1186/s12885-016-2670-x.

BRCA1-associated protein 1 deficiency in lung adenocarcinoma predicts poor outcome and increased tumor invasion.

Shen C1,2,3, Wang Y4, Wei P1,2,3, Du X5,6,7.

Author information

1
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.
2
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
3
Institute of Pathology, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China.
4
Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
5
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. dx2008cn@163.com.
6
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. dx2008cn@163.com.
7
Institute of Pathology, Fudan University Shanghai Cancer Center, No.270, Dong'an Road, Xuhui District, Shanghai, 200032, China. dx2008cn@163.com.

Abstract

BACKGROUND:

The 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.

METHODS:

A 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.

RESULTS:

BAP1 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.

CONCLUSIONS:

We 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.

KEYWORDS:

BAP1; Invasion; Lung adenocarcinoma; Tumor suppressor

PMID:
27553041
PMCID:
PMC4994180
DOI:
10.1186/s12885-016-2670-x
[Indexed for MEDLINE]
Free PMC Article

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