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Copy number variation of ubiquitin- specific proteases genes in blood leukocytes and colorectal cancer.
Cancer Biology & Therapy ( IF 4.4 ) Pub Date : 2020-05-04 , DOI: 10.1080/15384047.2020.1750860
Tian Tian 1 , Haoran Bi 1 , Yupeng Liu 1 , Guangxiao Li 1 , Yiwei Zhang 1 , Liming Cao 1 , Fulan Hu 1 , Yashuang Zhao 1 , Huiping Yuan 2
Affiliation  

Ubiquitin-specific proteases (USPs) play important roles in the regulation of many cancer-related biological processes. USPs copy number variation (CNVs) may affect the risk and prognosis of colorectal cancer (CRC). We detected CNVs of USPs genes in 468 matched CRC patients and controls, estimated the associations between the USPs genes CNVs and CRC risk and prognosis and their interactions with environmental factors on CRC risk. Finally, we generated five CRC risk predictive models with different CNVs patterns combining with environmental factors (EF). We identified significant association between CYLD deletion and CRC risk (ORadj = 4.18, 95% CI: 2.03–8.62), significant association between USP9X amplification and CRC risk (ORadj = 2.30, 95% CI: 1.48–3.57), and significant association between USP11 deletion and CRC risk (ORadj = 3.49, 95% CI: 1.49–8.64). There were significant gene-environment and gene–gene interactions on CRC risk. The area under the receiver operating characteristic curve (AUC) of EF + SIG (deletion of CYLD and USP11, amplification of USP9X) model was significantly larger than any other models (AUC = 0.75, 95% CI: 0.74–0.77). We did not identify significant associations between CNVs of the three genes and CRC prognosis. CNVs of CYLD, USP9X, and USP11 are significantly associated with the risk of CRC. Gene-gene and gene–environment interactions might also play an important role in the development of CRC.



中文翻译:

血液白细胞和结直肠癌中泛素特异性蛋白酶基因的拷贝数变异。

泛素特异性蛋白酶 (USP) 在许多癌症相关生物过程的调节中发挥着重要作用。USP 拷贝数变异 (CNV) 可能会影响结直肠癌 (CRC) 的风险和预后。我们在 468 名匹配的 CRC 患者和对照中检测了 USP 基因的 CNV,估计了 USP 基因 CNV 与 CRC 风险和预后之间的关联,以及它们与环境因素对 CRC 风险的相互作用。最后,我们结合环境因素(EF)生成了五个具有不同 CNV 模式的 CRC 风险预测模型。我们发现 CYLD 缺失与 CRC 风险之间存在显着关联(OR adj  = 4.18,95% CI:2.03–8.62),USP9X 扩增与 CRC 风险之间存在显着关联(OR adj = 2.30,95  % CI:1.48–3.57),并且显着关联USP11 缺失与 CRC 风险之间的关联(OR adj  = 3.49,95% CI:1.49–8.64)。CRC 风险存在显着的基因-环境和基因-基因相互作用。EF + SIG(删除CYLD和USP11,扩增USP9X)模型的受试者工作特征曲线下面积(AUC)显着大于任何其他模型(AUC = 0.75,95% CI:0.74-0.77)。我们没有发现这三个基因的 CNV 与 CRC 预后之间存在显着关联。CYLD、USP9X 和 USP11 的 CNV 与 CRC 风险显着相关。基因与基因以及基因与环境的相互作用也可能在结直肠癌的发展中发挥重要作用。

更新日期:2020-05-04
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