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Decreased expression of BRCA1-associated protein 1 predicts unfavorable survival in gastric adenocarcinoma

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Tumor Biology

Abstract

BRCA1-associated protein 1 (BAP1) has been reported as a novel tumor suppressor, while in gastric adenocarcinoma, the function of this protein was still await to be uncovered. Based on a large group of patients with gastric adenocarcinoma, our study aimed to have a further understanding about the correlation of BAP1 expression and patients’ clinical outcomes. We performed quantitative PCR and Western blot to examine BAP1 expression in 38 cases of gastric adenocarcinoma samples and adjacent non-cancerous tissues. Immunochemistry was used to evaluate BAP1 expression in a large cohort of 474 paraffin-embedded specimens. The clinical and prognostic significance of BAP1 expression was statistically analyzed. Postoperative survival between groups was using Kaplan-Meier analysis. BAP1 was overexpressed in paracancerous normal mucosa compared with gastric cancer. Decreased BAP1 expression was associated with higher histologic grade (P = 0.044), tumor infiltration (P < 0.001), metastasis status (P = 0.023), and TNM stage (P < 0.001). Patients with low expression of BAP1 had shorter overall survival compared with those with high expression (P < 0.001). Patients’ survival in stage N0 could be stratified by the expression of BAP1. Multivariate analysis showed that in gastric adenocarcinoma, BAP1 expressing level was an independent prognostic factor (RR = 0.575, P < 0.001). Decreased expression of BAP1 suggests pessimistic prognosis for gastric adenocarcinoma patients. Further studies are warranted.

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Abbreviations

BAP1:

BRCA1-associated protein 1

TNM:

Tumor-node-metastasis

IHC:

Immunohistochemistry

RT-PCR:

Reverse transcription polymerase chain reaction

WB:

Western blot

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Acknowledgments

This work was worked supported by the National Natural Science Foundation of China (No. 81172565 and No. 81202135).

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    Authors and Affiliations

    1. State Key Laboratory of Oncology in South China, Department of Pathology, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, China

      Shumei Yan, Rongzhen Luo, Mayan Huang & Yong Li

    2. Department of Molecular Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, 33612, USA

      Fan He

    3. Department of Biological Science, University of Illinois, Chicago, IL, 60607, USA

      Huini Wu

    4. Department of Endoscopy, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, China

      Chunyu Huang

    5. State Key Laboratory of Oncology in South China, Department of Gastric and Pancreatic Surgery, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, No. 651, Dongfeng East Road, 510060, Guangzhou, Guangdong, China

      Zhiwei Zhou

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    1. Shumei Yan
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    Correspondence to Yong Li or Zhiwei Zhou.

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    Synopsis for table of contents

    In this study, we demonstrated that decreased BAP1 expression was associated with a shorter overall survival in gastric adenocarcinoma and may act an effective biomarker.

    Shumei Yan and Fan He contributed equally to this work.

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    Supplementary Figure 1

    OS and FP curves for 593 gastric adenocarcinoma patients according to their BAP1 expression status (output from online Kaplan Meier plotter database). A. OS curves: patients with low (n=296) and high (n=297) expression levels of BAP1 respectively. B. FP curves: the first time when tumor progression was detected among patients with low and high expression levels of BAP1 respectively (JPEG 23.9 MB)

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    Yan, S., He, F., Luo, R. et al. Decreased expression of BRCA1-associated protein 1 predicts unfavorable survival in gastric adenocarcinoma. Tumor Biol. 37, 6125–6133 (2016). https://doi.org/10.1007/s13277-015-3983-0

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    • DOI: https://doi.org/10.1007/s13277-015-3983-0

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