Maragh Samantha, Veltri Robert W, Lund Steven P, Mangold Leslie, Isharwal Sumit, Christudass Christhunesa S, Partin Alan W, Humphreys Elizabeth B, Sorbara Lynn, Srivastava Sudhir, Wagner Paul D
Biosystems and Biomaterials Division, National Institute of Standards and Technology, Gaithersburg, MD, USA.
Department of Urology, Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cancer Biomark. 2015;15(6):763-73. doi: 10.3233/CBM-150518.
A 3.4kb deletion (3.4kbΔ ) in mitochondrial DNA (mtDNA) found in histologically normal prostate biopsy specimens has been reported to be a biomarker for the increased probability of prostate cancer. Increased mtDNA copy number is also reported as associated with cancer.
Independent evaluation of these two potential prostate cancer biomarkers using formalin-fixed paraffin-embedded (FFPE) prostate tissue and matched urine and serum from a high risk cohort of men with and without prostate cancer.
Biomarker levels were detected via qPCR.
Both 3.4kbΔ and mtDNA levels were significantly higher in cancer patient FFPE cores (p= 0.045 and p= 0.070 respectively at > 90% confidence). Urine from cancer patients contained significantly higher levels of mtDNA (p= 0.006, 64.3% sensitivity, 86.7% specificity). Combining the 3.4kbΔ and mtDNA gave better performance of detecting prostate cancer than either biomarker alone (FFPE 73.7% sensitivity, 65% specificity; urine 64.3% sensitivity, 100% specificity). In serum, there was no difference for any of the biomarkers.
This is the first report on detecting the 3.4kbΔ in urine and evaluating mtDNA levels as a prostate cancer biomarker. A confirmation study with increased sample size and possibly with additional biomarkers would need to be conducted to corroborate and extend these observations.
据报道，在组织学正常的前列腺活检标本中发现的线粒体DNA（mtDNA）3.4kb缺失（3.4kbΔ）是前列腺癌发生概率增加的生物标志物。也有报道称线粒体DNA拷贝数增加与癌症有关。
使用福尔马林固定石蜡包埋（FFPE）前列腺组织以及来自有或无前列腺癌的高危男性队列的匹配尿液和血清，对这两种潜在的前列腺癌生物标志物进行独立评估。
通过定量聚合酶链反应（qPCR）检测生物标志物水平。
癌症患者FFPE组织芯中的3.4kbΔ和线粒体DNA水平均显著更高（置信度>90%时，p值分别为0.045和0.070）。癌症患者尿液中的线粒体DNA水平显著更高（p = 0.006，灵敏度64.3%，特异性86.7%）。将3.4kbΔ和线粒体DNA结合起来检测前列腺癌的性能优于单独使用任何一种生物标志物（FFPE组织：灵敏度73.7%，特异性65%；尿液：灵敏度64.3%，特异性100%）。血清中，任何生物标志物均无差异。
这是关于在尿液中检测3.4kbΔ以及评估线粒体DNA水平作为前列腺癌生物标志物的首篇报道。需要进行一项样本量更大且可能纳入其他生物标志物的验证研究，以证实并扩展这些观察结果。
