Abstract
Long non-coding RNA (lncRNA)-mediated competitive endogenous RNA (ceRNA) networks act as essential mechanisms in tumor initiation and progression, but their diagnostic and prognostic significance in prostate cancer (PCa) remains poorly understood. Presently, using the RNA expression data derived from multiple independent PCa-related studies, we constructed a high confidence and PCa-specific core ceRNA network by employing three lncRNA-gene inference approaches and key node filter strategies and then established a logistic model and risk score formula to evaluate its diagnostic and prognostic values, respectively. The core ceRNA network consists of 10 nodes, all of which are significantly associated with clinical outcomes. Combination of expression of the 10 ceRNAs with a logistic model achieved AUC of ROC and PR curve up to ∼96 and 99% in excluding normal prostate samples, respectively. Additionally, a risk score formula constructed with the ceRNAs exhibited significant association with disease-free survival. More importantly, utilizing the expression of RNAs in the core ceRNA network as a molecular signature, the TCGA-PRAD cohort was divided into four novel clinically relevant subgroups with distinct expression patterns, highlighting a feasible way for improving patient stratification in the future. Overall, we constructed a PCa-specific core ceRNA network, which provides diagnostic and prognostic value.
Highlights
As the most prevalent malignancy among men, prostate cancer (PCa) accounted for nearly 9.1% of all male cancer deaths in 2018, making it the fourth leading cause of cancer death in Americans (Siegel et al, 2018)
To enhance the reliability of this study, we integrated PCa-related mRNAs, miRNAs and Long non-coding RNA (lncRNA) derived from multiple independent traits
We used the gene transfer format (GTF) file for human retrieved from GENCODE project (Paraskevopoulou et al, 2012) to identify the lncRNAs and mRNAs from the overlapping differentially expressed genes
Summary
As the most prevalent malignancy among men, prostate cancer (PCa) accounted for nearly 9.1% of all male cancer deaths in 2018, making it the fourth leading cause of cancer death in Americans (Siegel et al, 2018). A complete understanding of PCa initiation and progression remains elusive because its pathogenesis involves an interplay among multiple risk ceRNA Network for Prostate Cancer factors (Henrik, 2003; Bostwick et al, 2004), such as age, genetics, lifestyle, etc. While the 5-year survival rate of early PCa patients is nearly 100% owing to the improvement in modern medications, those at the advanced stage have a 5-year survival rate of less than 30% (Yuk and Kwak, 2018). There is an urgent need for the development of clinically relevant biomarkers for early detection and prognosis prediction of PCa, which will increase the chances for effective treatment and improve our understanding of the underlying mechanisms. LncRNA, which has been reported to be closely involved in cancer occurrence and progression (Zhan et al, 2018; Hua et al, 2019), is defined as a type of RNAs without coding potential, which are more than 200 nucleotides in length (Perkel, 2013; Zampetaki et al, 2018)
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