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小核仁RNA特征(SNORS)可识别膀胱癌(BLCA)的临床结局和预后。

Small nucleolar RNAs signature (SNORS) identified clinical outcome and prognosis of bladder cancer (BLCA).

作者信息

Cao Rui, Ma Bo, Yuan Lushun, Wang Gang, Tian Ye

机构信息

Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050 China.

Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038 China.

出版信息

Cancer Cell Int. 2020 Jul 10;20:299. doi: 10.1186/s12935-020-01393-7. eCollection 2020.

Abstract

BACKGROUND

Small nucleolar RNAs (snoRNAs) are a new non-coding RNAs (ncRNAs), which have not been widely investigated and are identified to be involved in tumorigenesis. But the function of snoRNAs in BLCA has not been reported yet.

METHODS

SnoRNAs signature (SNORS) was constructed through LASSO cox regression analysis. Integrated analysis of candidate snoRNAs was performed to detect the correlation between copy number variation (CNV)/DNA methylation/protein/mRNA/alternative splicing (AS). Then we built a nomogram integrating independent prognostic factors to assist the clinical utility.

RESULTS

We have screened out 15 prognostic differentially expressed snoRNAs (DESs) and constructed SNORS consisting of 5 candidate snoRNAs which could appropriately stratify patients into low or high SNORS groups with distinct prognosis. Then we found 5 candidate snoRNAs might be regulated by their own CNV and DNA methylation. Moreover, 5 candidate snoRNAs were significantly correlated mRNA and alternative splicing (AS), which might regulate diverse biological process in tumorigenesis, such as "extracellular matrix", "epithelial-mesenchymal transition (EMT)", etc. signaling pathways. Furthermore, SNORS was an independent prognostic factor, which was strikingly correlated with clinical outcome. Through inporating with other variables, we have established a predictive nomogram, which was more effectively to predict prognosis than any other variables alone.

CONCLUSION

Our findings first highlighted an important role of snoRNAs in BLCA and established a potential prognostic model which could serve as a biomarker for BLCA.

摘要

背景

小核仁RNA(snoRNAs)是一类新的非编码RNA(ncRNAs),尚未得到广泛研究,且已被证实参与肿瘤发生。但snoRNAs在膀胱癌(BLCA)中的功能尚未见报道。

方法

通过LASSO Cox回归分析构建snoRNAs特征(SNORS)。对候选snoRNAs进行综合分析,以检测拷贝数变异(CNV)/DNA甲基化/蛋白质/mRNA/可变剪接(AS)之间的相关性。然后我们构建了一个整合独立预后因素的列线图,以辅助临床应用。

结果

我们筛选出15个预后差异表达的snoRNAs(DESs),并构建了由5个候选snoRNAs组成的SNORS,其可将患者适当地分为SNORS低分组或高分组,两组预后不同。然后我们发现5个候选snoRNAs可能受其自身的CNV和DNA甲基化调控。此外,5个候选snoRNAs与mRNA和可变剪接(AS)显著相关,这可能在肿瘤发生过程中调节多种生物学过程,如“细胞外基质”、“上皮-间质转化(EMT)”等信号通路。此外,SNORS是一个独立的预后因素,与临床结局显著相关。通过纳入其他变量,我们建立了一个预测列线图,其预测预后比任何其他单独变量更有效。

结论

我们的研究结果首次突出了snoRNAs在BLCA中的重要作用,并建立了一个潜在的预后模型,可作为BLCA的生物标志物。

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