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

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

doi:10.1186/s12935-020-01393-7

Abstract

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

Highlights

Small nucleolar RNAs are a new non-coding RNAs, which have not been widely investigated and are identified to be involved in tumorigenesis
This is the first study focusing on small nucleolar RNA (snoRNA) in Bladder cancer (BLCA). 2
The function annotation revealed that snoRNAs signature (SNORS) was enriched in “extracellular matrix”, “epithelial–mesenchymal transition (EMT)”, etc., which are so important for tumorigenesis of BLCA. 4

Summary

Introduction

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. Bladder cancer (BLCA) is a malignancy originated from urinary tract with high morbidity and mortality, which is reported as the 10th most common cancer with an estimated 549,000 new cases and 200,000 deaths in 2018 [1]. Epidemiological studies have identified that BLCA is a heterogeneous disease consisting of two major subtypes, non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), which have distinct incidence and prognosis. NMIBC, which comprises the majority of BLCA, has not penetrated the detrusor muscle layer and is a not that life threatening with a ~ 90% five-year survival rate at most [2,3,4]. Non-responders will recur or even invade into the detrusor muscle layer, progressing to MIBC, which make the therapy of BLCA more complex.

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