A Novel Alternative Splicing-based Prediction Model for Uteri Corpus Endometrial Carcinoma

Alternative splicing (AS) is crucial a mechanism by which the complexity of mammalian and viral proteom increased overwhelmingly. There lacks systematic and comprehensive analysis of the prognostic significance of AS profiling landscape for uteri corpus endometrial carcinoma (UCEC). In this study, univariate and multivariate Cox regression analyses were conducted to identify candidate survival-associated AS events curated from SpliceSeq for the construction of prognostic index (PI) models. A correlation network between splicing factor-related AS events and significant survival-associated AS events were constructed using Cytoscape 3.5. As consequence, 28281 AS events from 8137 genes were detected from 506 UCEC patients, including 2630 survival-associated AS events. Kaplan Meier survival analysis revealed that six of the seven PI models (AD, AP, AT, ME, RI and ALL) exhibited good performance in stratifying the prognosis of low risk and high risk group (P<0.05). Among the six PI models, PI-AT performed best with an area under curves (AUC) value of 0.758 from time-dependent receiver operating characteristic. Correlation network implicated potential regulatory mechanism of AS events in UCEC. PI models based on survival-associated AS events for UCEC in this study showed preferable prognosis-predicting ability and may be promising prognostic indicators for UCEC patients.Summary: This is the first study to systematically investigate the prognostic value of AS in UCEC. Findings in the presents study supported the clinical potential of AS for UCEC and shed light on the potential AS-associated molecular basis of UCEC.