Premium
Altered mitochondrial genome content signals worse pathology and prognosis in prostate cancer
Author(s) -
Kalsbeek Anton M. F.,
Chan Eva K. F.,
Grogan Judith,
Petersen Desiree C.,
Jaratlerdsiri Weerachai,
Gupta Ruta,
Lyons Ruth J.,
Haynes AnneMaree,
Horvath Lisa G.,
Kench James G.,
Stricker Phillip D.,
Hayes Vanessa M.
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23440
Subject(s) - prostate cancer , mitochondrial dna , prostate , cancer , medicine , pathology , disease , biology , oncology , genetics , gene
Background Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra‐glandular as well as inter‐patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. Methods Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue. DNA was extracted and qPCR performed to quantify the total amount of mtDNA as a ratio to genomic DNA. Differences in mtDNA content were compared for prostate cancer pathology features and disease outcomes. Results We showed a significantly reduced mtDNA content in prostate cancer compared with normal adjacent prostate tissue (mean difference 1.73‐fold, P ‐value <0.001). Prostate cancer with increased mtDNA content showed unfavorable pathologic characteristics including, higher disease stage (PT2 vs PT3 P ‐value = 0.018), extracapsular extension ( P ‐value = 0.02) and a trend toward an increased Gleason score ( P ‐value = 0.064). No significant association was observed between changes in mtDNA content and biochemical recurrence (median follow up of 107 months). Conclusions Contrary to other cancer types, prostate cancer tissue shows no universally depleted mtDNA content. Rather, the change in mtDNA content is highly variable, mirroring known prostate cancer genome heterogeneity. Patients with high mtDNA content have an unfavorable pathology, while a high mtDNA content in normal adjacent prostate tissue is associated with worse prognosis.