Purpose: Advanced prostate cancer represents a heterogeneous disease entity with differences in clinical behavior, response to therapy, and survival. We assessed whether we could distinguish poor from good prognosis patients at presentation in our clinic by means of quantifying circulating cell-free mitochondrial and genomic nucleic acids in plasma.
Experimental design: We collected plasma from 75 prostate cancer patients and from 14 subjects with benign disease. Nucleic acids were isolated, and mitochondrial DNA (mtDNA; 16S rRNA), mitochondrial RNA (mtRNA; cytochrome c oxidase subunit 1), and genomic DNA (U1A DNA) transcripts were quantified by real-time amplification. An association between cell-free nucleic acids and metastasis, prostate-specific antigen doubling time, and hemoglobin levels was determined. Multivariate Cox proportional hazard and survival estimation studies were done.
Results: We show that elevated mtDNA and mtRNA levels are present in plasma of prostate cancer patients with a poor 2-year survival (P = 0.02 and 0.003, respectively). Cancer patients with high plasma mitochondrial nucleic acids, using a calculated optimal cutoff point, show a decreased survival compared with patients with low levels (35% versus 73% cumulative survival for mtDNA and 21% versus 73% for mtRNA). Multivariate analysis indicates that mtRNA is an independent predictor of 2-year survival.
Conclusions: Quantification of plasma mitochondrial nucleic acids may be used to recognize patients with a poor prognosis. In advanced prostate cancer patients, mtRNA seemed the strongest predictor of overall survival and an independent prognostic factor for cancer-related death. Amplification of mitochondrial nucleic acids shows increased sensitivity and specificity over genomic DNA as diagnostic and prognostic marker in prostate cancer patients.