A Genomic-Clinicopathologic Nomogram for the Prediction of Lymph Node Invasion in Prostate Cancer

Abstract

Background. Lymph node status is important for treatment decision making in prostate cancer (PCa). We aimed to develop a genomic-clinicopathologic nomogram for the prediction of lymph node invasion (LNI) in PCa. Methods. Differentially expressed genes between LNI and non-LNI PCa samples were identified in the Cancer Genome Atlas database. Univariate Cox regression analysis and minimum redundancy maximum relevance were performed for gene selection. The synthetic minority oversampling technique (SMOTE) was conducted to balance the minority group (LNI group). Machine learning models were constructed in the training set and assessed in the validation set. Univariable logistic regression and multivariable logistic regression were applied to build a nomogram. Furthermore, the RNA-sequence data from our center were used to validate the expression levels of hub genes between five matched primary PCa and the corresponding LNI samples. Results. The 37-gene-based support vector machine (SVM) model had the optimal synthesized performance in the SMOTE-balanced training (area under the curve (AUC): 0.947) and validation (AUC: 0.901) sets. Incorporating the SVM-based risk score and the Gleason grade, the genomic-clinicopathologic nomogram demonstrated good prediction and calibration both in the SMOTE-balanced training (AUC: 0.946) and validation (AUC: 0.910) sets. The dysregulated expression of hub genes between PCa and LNI samples was also validated. Conclusion. The proposed nomogram combining the 37-gene-based SVM model with the Gleason grade had the potential to preoperatively predict LNI in PCa. Some of the hub genes should be prioritized for functional studies and mechanistic analyses.