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

Yan, Shumei; He, Fan; Luo, Rongzhen; Wu, Haoran; Huang, Mayan; Huang, Chunyu; Li, Yong; Zhou, Zhiwei

doi:10.1007/s13277-015-3983-0

Cited by 16 publications

(11 citation statements)

References 35 publications

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“…Interestingly, 1 of the 47 (2%) tumors had complete loss of BAP1 expression in the tumor cells, but maintained strong labeling in the adjacent stroma. While the significance of heterogeneous BAP1 expression in PDAC needs to be evaluated further, it is noteworthy that decreased BAP1 expression in patients with gastric and colorectal cancer is associated with poor prognosis (23,24). Copy number and mRNA expression analysis of patients with pancreatic adenocarcinoma from The Cancer Genome Atlas (n ¼ 149) revealed recurrent shallow deletion of BAP1 (28%, n ¼ 42; Supplementary Fig.…”

Section: Bap1 Cooperates With Krasg12d To Cause Pancreatic Adenocarcimentioning

confidence: 99%

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

Lee¹,

Pham²,

Chang³

et al. 2020

Cancer Research

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The deubiquitinating enzyme BAP1 is mutated in a hereditary cancer syndrome with a high risk for mesothelioma and melanocytic tumors. Here, we show that pancreatic intraepithelial neoplasia driven by oncogenic mutant KrasG12D progressed to pancreatic adenocarcinoma in the absence of BAP1. The Hippo pathway was deregulated in BAP1-deficient pancreatic tumors, with the tumor suppressor LATS exhibiting enhanced ubiquitin-dependent proteasomal degradation. Therefore, BAP1 may limit tumor progression by stabilizing LATS and thereby promoting activity of the Hippo tumor suppressor pathway. Significance: BAP1 is mutated in a broad spectrum of tumors. Pancreatic Bap1 deficiency causes acinar atrophy but combines with oncogenic Ras to produce pancreatic tumors. BAP1-deficient tumors exhibit deregulation of the Hippo pathway. See related commentary by Brekken, p. 1624

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Section: Bap1 Cooperates With Krasg12d To Cause Pancreatic Adenocarcimentioning

confidence: 99%

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

Lee¹,

Pham²,

Chang³

et al. 2020

Cancer Research

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“…Regarding UCHL1, research has shown that it could be a candidate biomarker and therapeutic target for GC metastasis, as UCHL1 promoted this process via the Akt and Erk1/2 pathways (29). BAP1 expression is downregulated in gastric carcinoma and its decreased expression was associated with a malignant phenotype (histological grade) and a more advanced TNM stage (30). Furthermore, low BAP1 expression was revealed to be associated with poor prognosis in patients with gastric adenocarcinoma and GC (30).…”

Section: Uchs and Gcmentioning

confidence: 99%

“…BAP1 expression is downregulated in gastric carcinoma and its decreased expression was associated with a malignant phenotype (histological grade) and a more advanced TNM stage (30). Furthermore, low BAP1 expression was revealed to be associated with poor prognosis in patients with gastric adenocarcinoma and GC (30).…”

Section: Uchs and Gcmentioning

confidence: 99%

The role of deubiquitinating enzymes in gastric cancer (Review)

et al. 2019

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The epigenetic regulation of gene expression (via DNA methylation, histone modification and microRNA interference) contributes to a variety of diseases, particularly cancer. Protein deubiquitination serves a key role in the mechanism underlying histone modification, and consequently influences tumor development and progression. Improved characterization of the role of ubiquitinating enzymes has led to the identification of numerous deubiquitinating enzymes (DUBs) with various functions. Gastric cancer (GC) is a highly prevalent cancer type that exhibits a high mortality rate. Latest analysis about cancer patient revealed that GC is sixth deadliest cancer type, which frequently occur in male (7.2%) than female (4.1%). Complex associations between DUBs and GC progression have been revealed in multiple studies; however, the molecular mechanism underpinning the metastasis and recurrence of GC is yet to be elucidated. Generally, DUBs were upregulated in gastric cancer. The relation of DUBs and tumor size, classification and staging was observed in GC. Besides, 5-yar survival rate of patients with GC is effeccted by expression level of DUBs. Among the highly expressed DUBs, specifically six DUBs namely UCHs, USPs, OTUs, MJDs, JAMMs and MCPIPs effect on this survival rate. Consequently, the association between GC and DUBs has received increasing attention in recent years. Therefore, in the present review, literature investigating the association between DUBs and GC pathophysiology was analyzed and critically appraised.

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“…These observations are in contrast to data described for most other tumor types that have been * Mean ± standard error of the mean analyzed for BAP1 alterations so far. Reduced BAP1 expression has been linked to poor prognosis and adverse tumor features in renal carcinoma [10][11][12], colorectal cancer [34], gastric adenocarcinoma [35], non-small cell lung cancer [8,9], gall bladder cancer [13] and uveal melanoma [16][17][18]36]. These data suggest that BAP1 may function differently in different tumor types.…”

Section: Discussionmentioning

confidence: 96%

Untitled

2019

Oncotarget

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Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samples linked with comprehensive pathological, clinical and molecular data and studied the immunohistochemical expression of BAP1. BAP1 expression was typically up regulated in cancers as compared to adjacent normal prostatic glands. In 15,857 cancers, BAP1 staining was weak in 3.3%, moderate in 41.6% and strong in 17.4%. Strong BAP1 staining was associated with advanced tumor stage (p<0.0001), high classical and quantitative Gleason grade (p<0.0001), lymph node metastasis (p<0.0001), a positive surgical margin (p=0.0019) and early biochemical recurrence (p<0.0001). BAP1 expression was linked to ERG-fusion type cancers, with strong BAP1 staining in 12% of ERG-negative, but 30% of ERG-positive cancers (p<0.0001). Subset analyses in 5,415 cancers with and 4,217 cancers without TMPRSS2:ERG fusion revealed that these associations with tumor phenotype and patient outcome were largely driven by the subset of ERG-negative tumors. Multivariate analysis revealed that the prognostic impact was independent of established prognostic features in ERG negative p<0.001) but not in ERG positive cancers. BAP1 expression was further linked to androgen receptor (AR) expression: Only 2% of AR-negative, but 33% of strongly AR expressing cancers had strong BAP1 expression (p<0.0001). In conclusion, this study shows that BAP1 up regulation is linked to prostate cancer progression and aggressiveness.

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

Cited by 16 publications

References 35 publications

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

The Tumor Suppressor BAP1 Regulates the Hippo Pathway in Pancreatic Ductal Adenocarcinoma

The role of deubiquitinating enzymes in gastric cancer (Review)

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