Comprehensive analysis of prognosis-related alternative splicing events in ovarian cancer.

RNA Biol

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu, China.

Published: January 2022

AI Article Synopsis

  • Ovarian cancer has a high incidence and poor prognosis, with evidence showing that abnormal alternative splicing (AS) may contribute to its development.
  • Researchers used public databases like TCGA to identify AS events linked to patient outcomes and created a model for prognosis prediction based on AS.
  • The study found eight significant AS events that help differentiate between high-risk and low-risk groups, with the low-risk group experiencing better outcomes and increased sensitivity to paclitaxel, and developed an improved prognosis model that combines AS risk scores with clinical features.

Article Abstract

Ovarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable model to predict patients' outcomes. Public database including The Cancer Genome Atlas (TCGA), TCGA SpliceSeq, and the Genomics of Drug Sensitivity in Cancer databases were used to detect the AS expression, immune cell infiltration and IC50. The prognosis-related AS model was constructed and validated by using Cox regression, LASSO regression, C-index, calibration plots, and ROC curves. A total of eight AS events (including FLT3LG|50942|AP) were selected to establish the prognosis-related AS model. Compared with high-risk group, low-risk group had a better outcome ( = 1.794e-06), was more sensitive to paclitaxel ( = 0.022), and higher proportions of plasma cells. We explored the upstream regulatory mechanisms of prognosis-related AS and found that two splicing factor and 156 tag single nucleotide polymorphisms may be involved in the regulation of prognosis-related AS. In order to assess patient prognosis more comprehensively, we constructed a clinically applicable model combining risk score and clinicopathological features, and the 1 -, and 3-year AUCs of the clinically applicable model were 0.812, and 0.726, which were 7.5% and 3.3% higher than that of the risk score. We constructed a prognostic signature for OV patients and comprehensively analysed the regulatory characteristics of the prognostic AS events in OV.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9397453PMC
http://dx.doi.org/10.1080/15476286.2022.2113148DOI Listing

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