Assessment of biochemical recurrence of prostate cancer (Review)

Abstract

The assessment of the risk of biochemical recurrence (BCR) is critical in the management of males with prostate cancer (PC). Over the past decades, a comprehensive effort has been focusing on improving risk stratification; a variety of models have been constructed using PC-associated pathological features and molecular alterations occurring at the genome, protein and RNA level. Alterations in RNA expression (lncRNA, miRNA and mRNA) constitute the largest proportion of the biomarkers of BCR. In this article, we systemically review RNA-based BCR biomarkers reported in PubMed according to the PRISMA guidelines. Individual miRNAs, mRNAs, lncRNAs and multigene panels, including the commercially available signatures, Oncotype DX and Prolaris, will be discussed; details related to cohort size, hazard ratio and 95% confidence intervals will be provided. Mechanistically, these individual biomarkers affect multiple pathways critical to tumorigenesis and progression, including epithelial-mesenchymal transition (EMT), phosphatase and tensin homolog (PTEN), Wnt, growth factor receptor, cell proliferation, immune checkpoints and others. This variety in the mechanisms involved not only validates their associations with BCR, but also highlights the need for the coverage of multiple pathways in order to effectively stratify the risk of BCR. Updates of novel biomarkers and their mechanistic insights are considered, which suggests new avenues to pursue in the prediction of BCR. Additionally, the management of patients with BCR and the potential utility of the stratification of the risk of BCR in salvage treatment decision making for these patients are briefly covered. Limitations will also be discussed. Contents 1. Introduction 2. Stratification of BCR risk: An update 3. Searching methods for RNA-based BCR biomarkers 4. Gene expression-based biomarkers 5. Management of patients with biochemical recurrence 6. Perspectives

Construction of a Novel Multigene Panel Potently Predicting Poor Prognosis in Patients with Clear Cell Renal Cell Carcinoma

“…With current knowledge of non-coding RNA being important in the regulation of networks rather than specific genes [ 46 ], SigIQGAP1NW likely affects complex networks, a potential underlying reason for the impressive robustness observed in this multigene panel in assessing poor OS. This is consistent with the current consensus for the importance of a multigene panel to possess multiple features or affecting multiple processes for it to be clinically useful in patient management [ 47 ]. Along this line, our first demonstration of a significant upregulation of the HERC2P2 pseudogene in mRNA cluster 2 ( Figure 8 ), which is a more aggressive sub-type of ccRCCs than tumors in mRNA cluster 1 [ 14 ], further supports this research being novel and relevant.…”

Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

“…Mechanisms underlying PC initiation, progression, and therapy resistance have been extensively investigated. Risk assessment for PC prognosis using clinical features and molecular biomarkers has been actively pursued, leading to numerous biomarker candidates particularly for BCR risk assessment [ 61 ]. However, even with such extensive investigations, our understanding of PC progression remains incomplete and current prediction of PC relapse risk still needs substantial improvement.…”

DCBLD1 is associated with the integrin signaling pathway and has prognostic value in non-small cell lung and invasive breast carcinoma

“…For prostate adenocarcinoma, biochemical recurrence was evaluated instead of overall survival due to the low numbers of deceased patients. Biochemical recurrence in prostate cancer is defined as a rise in the blood level of prostate-specific antigen following surgery, and it precedes clinical disease recurrence 19 . Only 10 of 496 participants were deceased in the TCGA cohort (median follow-up: 30.5 years).…”