Wang Xiang-Yu, Wang Zheng, Huang Jian-Bo, Ren Xu-Dong, Ye Dan, Zhu Wen-Wei, Qin Lun-Xiu
1 Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
2 Molecular and Cell Biology Lab, Institute of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
Tumour Biol. 2017 Jun;39(6):1010428317699111. doi: 10.1177/1010428317699111.
BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.
BAP1是一种新发现的肿瘤抑制因子，其失活突变在肿瘤发展中起着关键作用。本研究旨在阐明BAP1突变在指导预后预测和临床分层方面的潜在价值。我们对多个数据库中的相关研究进行了全面分析，以确定BAP1突变对各种癌症患者总生存期和无病生存期的影响。最终分析纳入了来自21项研究的2457例患者。尽管汇总结果表明BAP1突变是总生存期（风险比=1.73；95%置信区间=1.23-2.42）和无病生存期（风险比=2.25；95%置信区间=1.47-3.45）的负性指标，但这种预后价值仅适用于葡萄膜黑色素瘤和透明细胞肾细胞癌，不适用于恶性胸膜间皮瘤或胆管癌。同样，BAP1突变仅在葡萄膜黑色素瘤和透明细胞肾细胞癌中与关键的临床病理特征相关。在葡萄膜黑色素瘤中，BAP1突变与SF3B1/EIF1AX突变呈负相关，BAP1突变型肿瘤的预后明显比SF3B1/EIF1AX突变型肿瘤差（p=0.028）。而在透明细胞肾细胞癌中，BAP1突变与PBRM1突变相互排斥，BAP1突变型透明细胞肾细胞癌的预后也明显比PBRM1突变型透明细胞肾细胞癌差（p=0.001）。我们的研究揭示了BAP1突变在不同类型癌症预后预测中独特的组织特异性意义。临床上，联合检测BAP1突变和其他驱动突变可能进一步实现更精确的分子分类，将葡萄膜黑色素瘤和透明细胞肾细胞癌患者分层为不同的亚组。
