分类： 生物学 >> 生物物理学 提交时间： 2016-05-15
摘要：Background: Bladder cancer (BC) is the fifth most common malignancy worldwide. The expression levels of microRNAs (miRNAs) in urine samples of BC patients have been demonstrated to be different from healthy people. Several studies focusing on the diagnostic value of urinary miRNAs for BC detection have been reported. The aim of this meta-analysis was to access the overall diagnostic accuracy comprehensively and quantitatively. Methods: PubMed, Embase, Web of Science, the Cochrane Library, and CNKI were searched without language restrictions for studies about the diagnostic value of miRNAs for BC. The pooled sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR, respectively), diagnostic odds ratio (DOR) were calculated using the random effects model. The summary receiver operating characteristic (SROC) curve was also generated and the area under the curve (AUC) was also reckoned to assess the diagnosis accuracy. Besides, Chi-square test and I-2 test were used to assess the heterogeneity between studies. Publication bias was evaluated by the Deeks' funnel plot asymmetry test. Results: Fourteen studies were included in this meta-analysis, with a total of 1,128 BC patients and 1,057 matched controls. The overall sensitivity, specificity, PLR, NLR and DOR of urinary miRNAs for the diagnosis of BC were 0.71 (95% CI: 0.67-0.75), 0.75 (95% CI: 0.70-0.79), 2.8 (95% CI: 2.3-3.4), 0.39 (95% CI: 0.33-0.46) and 7 (95% CI: 5-10), respectively. The area under the SROC curve was 0.79. Subgroup analyses suggested that the ethnicity and miRNA profiling had an obvious influence on the diagnostic accuracy. Conclusion: The current analysis suggested that urinary miRNA panels may be a promising noninvasive biomarker in the diagnosis of BC.
分类： 生物学 >> 生物物理学 提交时间： 2016-05-12
Lin, Youcheng
Xu, Abai
Zou, Yong
Wu, Xun
Liu, Chunxiao
Huang, Yi
Wang, Yongqiang
Zou, Xiaowen
Zhang, Meng
Fu, Yu
Cai, Zhiming
Wu, Song
Yang, Zhao
Yang, Zhao
Liu, Huan
Li, Feida
Sun, Da
Zhang, Duo
Liu, Hongjie
Wang, Yu
摘要：The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway has been identified as an important pathway in renal cell carcinoma (RCC). We have reported a nonsense mutation in PIK3R1, which encodes the regulatory subunit of PI3K, in a metastatic RCC (mRCC), while the mutation was absent in the corresponding primary RCC (pRCC). To identify the function of PIK3R1 in RCC, we examined its expression in normal kidney, pRCC and mRCC by immunohistochemistry and real-time polymerase chain reaction. The expression of PIK3R1 significantly decreased in pRCC and was further reduced in mRCC compared with normal tissue. Besides, its expression levels were negatively correlated with T-category of tumor stage. Additionally, 786-O and A-704 cells with PIK3R1 depletion introduced by CRISPR/Cas9 system displayed enhanced proliferation, migration and epithelial-mesenchymal transition (EMT), and acquired a stem-like phenotype. Moreover, the PIK3R1 depletion promoted the phosphorylation of AKT in the cells. The knockdown of AKT by shRNA reduced p-GSK3 beta and CTNNB1 expression in the cells, while the depletion of CTNNB1 impaired stem-like phenotype of the cells. Overall, PIK3R1 down-regulation in RCC promotes propagation, migration, EMT and stem-like phenotype in renal cancer cells through the AKT/GSK3 beta/CTNNB1 pathway, and may contribute to progression and metastasis of RCC.
分类： 生物学 >> 生物物理学 >> 肿瘤学 提交时间： 2016-05-11
Li, Chong
Yang, Zhao
Du, Ying
He, Luyun
Fan, Zusen
Li, Chong
Wu, Song
Cai, Zhiming
Wang, Haifeng
Wang, Jiansong
Bi, Xingang
摘要：Bladder cancer is one of the most common malignant tumors worldwide. Bladder cancer stem cells (BCSCs) have been isolated recently but have not been defined yet. Here we sorted BCSCs from bladder tumor tissues or normal bladder stem cells (NBBCs) from adjacent normal bladder tissues. We found that the C228T mutation (chr5, 1, 295, 228 C > T) of TERT promoter frequently occurs in BCSCs, but not exist in NBBCs. Importantly, introducing the C228T mutation in NBBCs causes TERT overexpression and transformation of bladder cancer. Restoration of the C228T mutation to T228C in BCSCs can recover the TERT expression to a basal level and abolish tumor formation. Additionally, the C228T mutation of TERT promoter triggers TERT expression leading to increased telomerase activity. TERT expression levels are consistent with clinical severity and prognosis of bladder cancer.
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