Abstract
BackgroundCircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers. However, the expression of circRNAs in esophageal squamous cell carcinoma (ESCC) remain unknown. We aim to identify prognostic circRNAs and construct a circRNA-related signature in ESCC.MethodsRNA sequencing was used to test the circRNA expression profiles of 73 paired ESCC tumor and normal tissues after RNase R enrichment. Bioinformatics methods, such as principal component analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE) algorithm, unsupervised clustering and hierarchical clustering were performed to analyze the circRNA expression characteristics. Univariate cox regression analysis, random survival forests-variable hunting (RSFVH), Kaplan–Meier analysis, multivariable Cox regression and ROC (receiver operating characteristic) curve analysis were used to screen the prognostic circRNA signature. Real-time quantitative PCR (qPCR) and fluorescence in situ hybridization(FISH) in 125 ESCC tissues were performed.ResultsCompared with normal tissues, there were 11651 differentially expressed circRNAs in cancer tissues. A total of 1202 circRNAs associated with ESCC prognosis (P < 0.05) were identified. Through bioinformatics analysis, we screened a circRNA signature including four circRNAs (hsa_circ_0000005, hsa_circ_0007541, hsa_circ_0008199, hsa_circ_0077536) which can classify the ESCC patients into two groups with significantly different survival (log rank P < 0.001), and found its predictive performance was better than that of the TNM stage(0.84 vs. 0.66; 0.65 vs. 0.62). Through qPCR and FISH experiment, we validated the existence of the screened circRNAs and the predictive power of the circRNA signature.ConclusionThe prognostic four-circRNA signature could be a new prognostic biomarker for ESCC, which has high clinical application value.
Highlights
CircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers
After next-generation sequencing (NGS) analysis, a total of 128,165 circRNAs were detected from these samples, of which 25,945 circRNA candidates were consistent with circBase (Fig. 1a)
We found that highly abundant circular transcripts were often extensive and can be detected in most esophageal squamous cell carcinoma (ESCC) samples
Summary
CircRNAs with tissue-specific expression and stable structure may be good tumor prognostic markers. The expression of circRNAs in esophageal squamous cell carcinoma (ESCC) remain unknown. We aim to identify prognostic circRNAs and construct a circRNA-related signature in ESCC. Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor with squamous cell differentiation, accounting for 90% of esophageal cancer. The incidence of ESCC shows significant regional differences and is decreasing in recent years, it is still one of. The 5-year survival rate of ESCC is reported to be only 10% [2]. In the past few decades, the progress of ESCC treatment have not significantly increased the life expectancy of patients [3, 4]. ESCC patients urgently need prognostic markers that can evaluate disease progression and clinical outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
