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Abstract
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.
Highlights
Endometrial cancer (EC), referred to as uterine corpus endometrial cancer (UCEC), is one of the most common gynaecologic malignancy all over the world and most frequently occurs in postmenopausal women [1, 2]
Existing risk stratification for UCEC patients based on morphological classification had limited power in predicting the overall survival conditions of UCEC patients and it remained unsolved to find effective prognostic indicator for UCEC patients
Accumulated evidence suggested that Alternative splicing (AS) exerted vast influence on the biological events of human cancers [22,23,24], which enlightened us that the aberrant AS profiles in UCEC may provide valuable prognostic information
Summary
Endometrial cancer (EC), referred to as uterine corpus endometrial cancer (UCEC), is one of the most common gynaecologic malignancy all over the world and most frequently occurs in postmenopausal women [1, 2]. Advances in genomic sequencing has made precision medicine the main melody of current anti-cancer treatment and we attempted to seek reliable genetic changes from the aspect of alternative splicing (AS) to enhance the individualized prognosis prediction of UCEC patients [6]. In UCEC, multiple splice variants of estrogen receptor (ER) and progesterone receptor (PR), two vital molecules that played important roles in the initiation and development of UCEC, were discovered as the results of AS [14]. These receptor variants have been reported to affect the carcinogenesis of UCEC with distinct functions [14,15,16]. We pursued the present study on systematically exploring the prognostic significance of AS events in UCEC based on RNA sequencing data in TCGA in order to find promising prognostic predictors for UCEC patients
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