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Published on: January 12, 2020
Derivation, Comprehensive Analysis, and Assay Validation of a Pyroptosis-Related lncRNA Prognostic Signature in
Xueyan Cao1,2, Qingquan Zhang3,2, Yu Zhu1,2
1Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong, China.
Background:
Pyroptosis is regulated by long non-coding RNAs (lncRNAs) in ovarian cancer (OC). Therefore, a comprehensive analysis of pyroptosis-related lncRNAs (PRLs) in OC is crucial for developing therapeutic strategies and survival prediction.
Methods:
Based on public database raw data, mutations in the landscape of pyroptosis-related genes (PRGs) in patients with OC were investigated thoroughly. PRLs were identified by calculating Pearson correlation coefficients. Cox and LASSO regression analyses were performed on PRLs to screen for lncRNAs participating in the risk signature. Furthermore, receiver operating characteristic (ROC) curves, Kaplan-Meier survival analyses, decision curve analysis (DCA) curves, and calibration curves were used to confirm the clinical benefits. To assess the ability of the risk signature to independently predict prognosis, it was included in a Cox regression analysis with clinicopathological parameters. Two nomograms were constructed to facilitate clinical application. In addition, potential biological functions of the risk signature were investigated using gene function annotation. Subsequently, immune-related landscapes and BRCA1/2 mutations were compared in different risk groups using diverse bioinformatics algorithms. Finally, we conducted a meta-analysis and in-vitro assays on alternative lncRNAs.
Results:
A total of 374 patients with OC were randomized into training and validation cohorts (7:3). A total of 250 PRLs were selected from all the lncRNAs. Subsequently, a risk signature (DICER1-AS1, MIR600HG, AC083880.1, AC109322.1, AC007991.4, IL6R-AS1, AL365361.1, and AC022098.2) was constructed to distinguish the risk of patient survival. The ROC curve, K-M analysis, DCA curve, and calibration curve indicated excellent predictive performance for determining overall survival (OS) based on the risk signature in each cohort (p < 0.05). The Cox regression analysis indicated that the risk signature was an independent prognostic factor for OS (p < 0.05). Moreover, significant differences in the immune response and BRCA1 mutations were identified in different groups distinguished by the risk signature (p < 0.05). Interestingly, in-vitro assays showed that an alternative lncRNA (DICER1-AS1) could promote OC cell proliferation.
Conclusion:
The PRL risk signature could independently predict overall survival and guide treatment in patients with OC.
