Improvement in prediction of prostate cancer prognosis with somatic mutational signatures

Prostate cancer is a leading male malignancy worldwide, while the prognosis prediction remains quite inaccurate. The study aimed to observe whether there was an association between the prognosis of prostate cancer and genetic mutation profile, and to build an accurate prognostic predictor based on the genetic signatures. The patients diagnosed of prostate cancer from The Cancer Genomic Atlas were used for prognostic stratification, while the somatic gene mutation profiles were compared between different prognostic groups. The genetic features were further used for training machine-learning models to predict prostate cancer prognosis. No significant gene with somatic mutation rate difference was found between prognostic groups of prostate cancer. Total 43 atypical genes were screened for building a support vector machine model to predict prostate cancer prognosis, with an average accuracy of 66% and 64% for 5-fold cross-validation or training-testing evaluation respectively. When combined with the National Institute for Health and Care Excellence (NICE) features, the model could be further improved, with the 5-fold cross-validation accuracy of ~71%, much better than NICE itself (62%). To our knowledge, for the first time, the research studied the relationship of genome-wide somatic mutations with prostate prognosis, and developed an effective prognostic prediction model with the atypical genetic signatures.