scholarly journals Characteristics and prognostic value of potential dependency genes in clear cell renal cell carcinoma based on a large-scale CRISPR-Cas9 and RNAi screening database DepMap

2021 ◽  
Vol 18 (9) ◽  
pp. 2063-2075
Author(s):  
Bowen Shi ◽  
Jie Ding ◽  
Jun Qi ◽  
Zhengqin Gu
2021 ◽  
Author(s):  
Zhicheng Liu ◽  
Dongxu Lin ◽  
Linmeng Zhang ◽  
Chen Yang ◽  
Bin Guo ◽  
...  

Abstract Background The emerging of targeted therapies has revolutionized the treatment modalities of advanced clear cell renal cell carcinoma (ccRCC) over the past fifteen years. However, lack of personalized treatment limits the development of effective clinical guidelines and improvement of patient prognosis. In this study, large-scale genomic profiles of ccRCC cohorts were exploited for conducting an integrative analysis. Method Based on synthetic lethality (SL), a concept that simultaneous losses of two genes cause cell death while a single loss does not, we sought to develop a computational pipeline to infer potential SL partners of ccRCC. Drug response prediction were received from three pharmacological databases to select agents which are likely to be effective in precisely treating patients with target gene mutation. Results We developed a credible method to identify SL pairs and determined a list of 72 candidate pairs which might be utilized to selectively eliminate tumors with genetic aberrations through SL partners of specific mutations. Further analysis identified BRD4 and PRKDC as novel medicine targets for patients with BAP1 mutations. After mapping these target genes to comprehensive drug datasets, two agents (BI-2536 and PI-103) were found to have considerable therapeutic potential in BAP1 mutant tumors. Conclusion Overall, our findings provide insight into the overview of ccRCC mutation patterns and offer novel opportunities for improving individualized cancer treatment.


Aging ◽  
2019 ◽  
Vol 11 (23) ◽  
pp. 11474-11489 ◽  
Author(s):  
Bangbei Wan ◽  
Bo Liu ◽  
Yuan Huang ◽  
Gang Yu ◽  
Cai Lv

2021 ◽  
Vol Volume 13 ◽  
pp. 6673-6687
Author(s):  
Hanrong Li ◽  
Huiming Jiang ◽  
Zhicheng Huang ◽  
Zhilin Chen ◽  
Nanhui Chen

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Wen-Hao Xu ◽  
Shen-Nan Shi ◽  
Yue Xu ◽  
Jun Wang ◽  
Hong-Kai Wang ◽  
...  

Abstract Background Growing evidence has demonstrated immune reactivity as a confirmed important carcinogenesis and therapy efficacy for clear cell renal cell carcinoma (ccRCC). Aquaporin 9 (AQP9) is involved in many immune-related signals; however, its role in ccRCC remains to be elucidated. This study investigated AQP9 expression in tumor tissues and defined the prognostic value in ccRCC patients. Methods A total of 913 ccRCC patients with available RNA-sequence data from the Cancer Genome Atlas (TCGA) database and Fudan University Shanghai Cancer Center (FUSCC) were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained and validated using multiple datasets. A partial likelihood test from Cox regression analysis was developed to address the influence of independent factors on progression-free survival (PFS) and overall survival (OS). The Kaplan–Meier method and log-rank test were performed to assess survival. Receiver operating characteristic (ROC) curves were used to describe binary classifier value of AQP9 using area under the curve (AUC) score. Functional enrichment analyses and immune infiltration analysis were used to describe significantly involved hallmark pathways of hub genes. Results Significantly elevated transcriptional and proteomic AQP9 expressions were found in ccRCC samples. Increased AQP9 mRNA expression was significantly associated with advanced clinicopathological parameters and correlated with shorter PFS and OS in TCGA and FUSCC cohorts (p < 0.001). ROC curves suggested the significant diagnostic and prognostic ability of AQP9 (PFS, AUC = 0.823; OS, AUC = 0.828). Functional annotations indicated that AQP9 is involved in the most significant hallmarks including complement, coagulation, IL6/JAK–STAT3, inflammatory response and TNF-alpha signaling pathways. Conclusion Our study revealed that elevated AQP9 expression was significantly correlated with aggressive progression, poor survival and immune infiltrations in ccRCC patients, and we validated its prognostic value in a real-world cohort. These data suggest that AQP9 may act as an oncogene and a promising prognostic marker in ccRCC.


2019 ◽  
Vol 121 (3) ◽  
pp. 2571-2581 ◽  
Author(s):  
Shiyi Liu ◽  
Saijiao Li ◽  
Yanqing Wang ◽  
Feiyan Wang ◽  
Li Zhang ◽  
...  

2020 ◽  
Vol 11 (22) ◽  
pp. 6591-6600 ◽  
Author(s):  
Zhenpeng Zhu ◽  
Anbang He ◽  
Lanruo Lin ◽  
Chunru Xu ◽  
Tianyu Cai ◽  
...  

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