Abstract
Alternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. There are no reliable features to predict survival outcomes for ovarian cancer patients. In this study, comprehensive profiling of AS events was conducted by integrating AS data and clinical information of ovarian serous cystadenocarcinoma (OV). Survival-related AS events were identified by Univariate Cox regression analysis. Then, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis were used to construct the prognostic signatures within each AS type. Furthermore, we established a splicing-related network to reveal the potential regulatory mechanisms between splicing factors and candidate AS events. A total of 730 AS events were identified as survival-associated splicing events, and the final prognostic signature based on all seven types of AS events could serve as an independent prognostic indicator and had powerful efficiency in distinguishing patient outcomes. In addition, survival-related AS events might be involved in tumor-related pathways including base excision repair and pyrimidine metabolism pathways, and some splicing factors might be correlated with prognosis-related AS events, including SPEN, SF3B5, RNPC3, LUC7L3, SRSF11 and PRPF38B. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development.
Highlights
Alternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma
The splicing isoforms of specific genes act as the drivers of cancer, which are related to tumor development, proliferation, metastasis, survival and drug resistance[6,7]
Our results showed that the final model by integrating seven types of AS events could significantly distinguish patients with different clinical outcomes and had the highest reliable efficiency
Summary
Alternative splicing (AS) events associated with oncogenic processes present anomalous perturbations in many cancers, including ovarian carcinoma. Our study constructs an independent prognostic signature for predicting ovarian cancer patients’ survival outcome and contributes to elucidating the underlying mechanism of AS in tumor development. Alternative splicing (AS) is a pre-mRNA processing pathway in which introns are selectively removed to produce functionally distinct m RNAs1 It is an important posttranscriptional regulatory mechanism and serves as the main driving force contributing to proteomic and transcriptome diversity in multicellular eukaryotes[2]. We conducted an in-depth analysis of AS profiling based on ovarian serous cystadenocarcinoma cohort from the Cancer Genome Atlas database, evaluating the survival-associated AS events. Functional enrichment analysis and splicing factor regulatory network were performed These results may contribute to understand the underlying mechanisms of AS in ovarian cancer progression
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