Kalsbeek Anton M F, Chan Eva K F, Grogan Judith, Petersen Desiree C, Jaratlerdsiri Weerachai, Gupta Ruta, Lyons Ruth J, Haynes Anne-Maree, Horvath Lisa G, Kench James G, Stricker Phillip D, Hayes Vanessa M
Laboratory for Human Comparative and Prostate Cancer Genomics, Genomics and Epigenetics Division, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
School of Medical Sciences, University of New South Wales Sydney, Randwick, New South Wales, Australia.
Prostate. 2018 Jan;78(1):25-31. doi: 10.1002/pros.23440. Epub 2017 Nov 14.
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.
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.
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).
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.
许多癌症中，线粒体基因组（mtDNA）含量会减少。在前列腺癌中，腺体内以及患者间存在mtDNA拷贝数变异。在本研究中，我们确定mtDNA含量是否可作为前列腺癌分期和预后的预测指标。
在手术时获取115例患者的新鲜前列腺癌活检组织。所有组织芯均进行病理检查，随后分离出癌组织和正常组织。提取DNA并进行qPCR，以量化mtDNA总量与基因组DNA的比值。比较前列腺癌病理特征和疾病预后的mtDNA含量差异。
我们发现，与相邻正常前列腺组织相比，前列腺癌中的mtDNA含量显著降低（平均差异1.73倍，P值<0.001）。mtDNA含量增加的前列腺癌表现出不良病理特征，包括更高的疾病分期（PT2 vs PT3，P值 = 0.018）、包膜外侵犯（P值 = 0.02）以及Gleason评分增加的趋势（P值 = 0.064）。未观察到mtDNA含量变化与生化复发之间存在显著关联（中位随访107个月）。
与其他癌症类型不同，前列腺癌组织中mtDNA含量并非普遍减少。相反，mtDNA含量的变化高度可变，反映了已知的前列腺癌基因组异质性。mtDNA含量高的患者病理表现不良，而相邻正常前列腺组织中mtDNA含量高与预后较差相关。
