Mitochondria Dysfunction-Mediated Molecular Subtypes and Gene Prognostic Index for Prostate Cancer Patients Undergoing Radical Prostatectomy or Radiotherapy

BACKGROUND: Given the age relevance of prostate cancer (PCa) and the role of mitochondrial dysfunction (MIDS) in aging, we orchestrated molecular subtypes and identified key genes for PCa from the perspective of MIDS. METHODS: Cluster analysis, COX regression analysis, function analysis, and tumor immune environment were conducted. We performed all analyses using software R 3.6.3 and its suitable packages. RESULTS: CXCL14, SFRP4, and CD38 were eventually identified to classify the PCa patients in The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) dataset into two distinct clusters. Patients in the cluster 2 had shorter BCR-free survival than those in the cluster 1 in terms of both TCGA database and GEO dataset. We divided the patients from the TCGA database and the GEO dataset into high- and low-risk groups according to the median of MIDS-related genetic prognostic index. For patients in the TCGA database, the biochemical recurrence (BCR) risk in high-risk group was 2.34 times higher than that in low-risk group. Similarly, for patients in the GEO dataset, the risk of BCR and metastasis in high-risk group was 2.35 and 3.04 times higher than that in low-risk group, respectively. Cluster 2 was closely associated with advanced T stage and higher Gleason score for patients undergoing radical prostatectomy or radiotherapy. For patients undergoing radical prostatectomy, the number of CD8(+) T cells was significantly lower in cluster 2 than in cluster 1, while cluster 2 had significantly higher stromal score than cluster 1. For patients undergoing radical radiotherapy, cluster 2 had significantly higher level of CD8(+) T cells, neutrophils, macrophages, dendritic cells, stromal score, immune score, and estimate score, but showed lower level of tumor purity than cluster 1. CONCLUSIONS: We proposed distinctly prognosis-related molecular subtypes at genetic level and related formula for PCa patients undergoing radical prostatectomy or radiotherapy, mainly to provide a roadmap for precision medicine.