Mutator-Derived lncRNA Landscape: A Novel Insight Into the Genomic Instability of Prostate Cancer.

Background: Increasing evidence has emerged to reveal the correlation between genomic instability and long non-coding RNAs (lncRNAs). The genomic instability-derived lncRNA landscape of prostate cancer (PCa) and its critical clinical implications remain to be understood. Methods: Patients diagnosed with PCa were recruited from The Cancer Genome Atlas (TCGA) program. Genomic instability-associated lncRNAs were identified by a mutator hypothesis-originated calculative approach. A signature (GILncSig) was derived from genomic instability-associated lncRNAs to classify PCa patients into high-risk and low-risk groups. The biochemical recurrence (BCR) model of a genomic instability-derived lncRNA signature (GILncSig) was established by Cox regression and stratified analysis in the train set. Then its prognostic value and association with clinical features were verified by Kaplan-Meier (K-M) analysis and receiver operating characteristic (ROC) curve in the test set and the total patient set. The regulatory network of transcription factors (TFs) and lncRNAs was established to evaluate TF-lncRNA interactions. Results: A total of 95 genomic instability-associated lncRNAs of PCa were identified. We constructed the GILncSig based on 10 lncRNAs with independent prognostic value. GILncSig separated patients into the high-risk ( Conclusion: In summary, we developed a prognostic signature of BCR based on genomic instability-associated lncRNAs for PCa, which may provide new insights into the epigenetic mechanism of BCR.