A seven-gene prognosis model to predict biochemical recurrence for prostate cancer based on the TCGA database

Abstract

Background: The incidence rate of prostate cancer is increasing rapidly. This study aims to explore the gene-associated mechanism of prostate cancer biochemical recurrence (BCR) after radical prostatectomy and to construct a biochemical recurrence of prostate cancer prognostic model.

Methods: The DEseq2 R package was used for the differential expression of mRNA. The ClusterProfiler R package was used to analyze the functional enrichment of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to explore related mechanisms. The Survival, Survminer, and My.stepwise R packages were used to construct the prognostic model to predict the biochemical recurrence-free probability. The RMS R package was used to draw the nomogram. For evaluating the prognostic model, the timeROC R package was used to draw the time-dependent ROC curve (receiver operating characteristic curve).

Result: To investigate the association between mRNA and prostate cancer, we performed differential expression analysis on the TCGA (The Cancer Genome Atlas) database. Seven protein-coding genes (VWA5B2, ARC, SOX11, MGAM, FOXN4, PRAME, and MMP26) were picked as independent prognostic genes by regression analysis. Based on their Cox coefficient, a risk score formula was proposed. According to the risk scores, patients were divided into high- and low-risk groups based on the median score. Kaplan-Meier plot curves showed that the low-risk group had a better biochemical recurrence-free probability compared to the high-risk group. The 1-year, 3-year, and 5-year AUCs (areas under the ROC curve) of the model were 77%, 81%, and 86%, respectively. In addition, we built a nomogram based on the result of multivariate Cox regression analysis. Furthermore, we select the GSE46602 dataset as our external validation. The 1-year, 3-year, and 5-year AUCs of BCR-free probability were 83%, 82%, and 80%, respectively. Finally, the levels of seven genes showed a difference between PRAD tissues and adjacent non-tumorous tissues.

Conclusions: This study shows that establishing a biochemical recurrence prediction prognostic model comprising seven protein-coding genes is an effective and precise method for predicting the progression of prostate cancer.

Keywords: biochemical recurrence; nomogram; prognosis model; prostate cancer; the cancer genome atlas (TCGA).