The Landscape And Prognositic Value Of Circular RNA In Esophageal Squamous Cell Carcinoma

PURPOSEEsophageal squamous cell carcinoma?ESCC?is a highly invasive and malignant gastrointestinal tumor with a poor prognosis.The expression specificity in different tissues or different developmental stages and the stability of the closed-loop structure make it possible for circular RNA to become a good prognostic marker.The aim of this study was to explore the circRNA expression pattern of ESCC,identify prognostic circRNAs and construct a circRNA-related nodle for predicting ESCC survival.MethodsThe ESCC circRNA expression profile was tested by RNA-seq in 73 paired tumor and normal tissues.Bioinformatics methods such as principal component analysis?PCA?,t-distributed Stochastic Neighbor Embedding?t-SNE?algorithm,unsupervised clustering and hierarchical clustering,were used to analyze the circRNA expression characteristics.These 73 pairs of ESCC patients were treated as the training set and another independent cohort of 125 postoperative patients with ESCC was used as the test set.Real-time quantitative PCR?qPCR?,agarose gel electrophoresis and RNA fluorescence in situ hybridization(FISH were performed.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 screen the prognostic circRNA signature.Results1.Bioinformatics analyses showed that the circRNA expression patterns of normal tissues and ESCC tissues were significantly different Compared with normal tissues,there were 11651 differentially expressed circular RNAs in cancer tissues out of 31542 circRNAs detected by CIRI.Among them,a total of 1202 differential circRNAs associated with survival of ESCC patients?P<0.05?were identified.2.After a variety of statistical and machine learning analyses,we screened a circRNA signature including four circRNAs?hsa_circ₀000005,hsa_circ₀007541,hsa_circ₀008199,hsa_circ₀077536?with the best predictive performance.3.The signature can classify the ESCC patients into two groups with significantly different overall survival?median survival 19.2 months vs.>60 months,log rank P<0.001?.The test set confirmed the prognostic power of the signature?log rank P<0.001?.4.The expression of prognostic four circRNAs in ESCC tissues and cell lines were verified.ConclusionThe expression of circular RNA in esophageal squamous cell carcinomas was imbalanced.And the prognostic four-circRNA signature could be a new potential prognostic biomarker for the ESCC with high clinical value.