Prostate cancer is a major health burden, being the second most commonly diagnosed malignancy in men worldwide. Overtreatment represents a major problem in prostate cancer therapy, leading to significant long-term quality-of-life effects for patients and a broad socio-ecological burden. Biomarkers that could facilitate risk stratification of prostate cancer aggressiveness at the time of diagnosis may help to guide clinical treatment decisions and reduce overtreatment. Previous research on genetic variations in prostate cancer has shown that germline copy number variations as well as somatic copy number alterations are commonly present in cancer patients, altering a greater portion of the cancer genome than any other type of genetic variation. To investigate the effect of germline copy number variations on cancer aggressiveness we have compared genome-wide screening data from genomic DNA isolated from the blood of 120 patients with aggressive prostate cancer, 231 patients with non-aggressive prostate cancer and 87 controls with benign prostatic hyperplasia from the Prostate Cancer Study of Austria biobank using the Affymetrix SNP 6.0 array. We could show that patients with an aggressive form of prostate cancer had a higher frequency of copy number variations [mean count of copy number segments (CNS) = 12.9, median count of CNS = 9] compared to patients with non-aggressive prostate cancer (mean count of CNS = 10.4, median count of CNS = 8) or control patients diagnosed with benign prostatic hyperplasia (mean count of CNS = 9.3, median count of CNS = 8). In general, we observed that copy number gain is a rarer event, compared to copy number loss within all three patient groups. Furthermore, we could show a significant effect of copy number losses located on chromosomes 8, 9 and 10 on prostate cancer aggressiveness (P = 0.040, P = 0.037 and P = 0.005, respectively). Applying a cross-validation analysis yielded an area under the curve of 0.63. Our study reports promising findings suggesting that copy number losses might play an important role in the establishment of novel biomarkers to predict prostate cancer aggressiveness at the time of diagnosis. Such markers could be used to facilitate risk stratification to reduce overtreatment of prostate cancer patients.

中文翻译：

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种系拷贝数变异的全基因组关联研究揭示了与前列腺癌侵袭性的关联。

前列腺癌是主要的健康负担，是全世界男性中第二常见的恶性肿瘤。过度治疗是前列腺癌治疗中的一个主要问题，导致对患者的重大长期生活质量影响和广泛的社会生态负担。在诊断时可促进前列腺癌侵袭风险分层的生物标志物可能有助于指导临床治疗决策并减少过度治疗。先前对前列腺癌遗传变异的研究表明，癌症患者中普遍存在种系拷贝数变异和体细胞拷贝数改变，与任何其他类型的遗传变异相比，改变的癌症基因组比例更大。为了研究种系拷贝数变异对癌症侵袭性的影响，我们比较了从120例侵袭性前列腺癌患者，231例非侵袭性前列腺癌患者和87例良性前列腺增生患者血液中分离的基因组DNA的全基因组筛选数据使用Affymetrix SNP 6.0阵列从奥地利生物库前列腺癌研究获得。我们可以证明，与非侵略性前列腺癌患者相比，侵略性前列腺癌患者具有更高的拷贝数变异频率[拷贝数片段平均数（CNS）= 12.9，CNS中位数= 9]（中枢神经系统平均计数= 10.4，中枢神经系统计数中位数= 8）或诊断为良性前列腺增生的对照患者（中枢神经系统平均计数= 9.3，中枢神经系统中位数= 8）。一般来说，我们观察到，与所有三个患者组中的拷贝数减少相比，拷贝数增加是一种罕见的事件。此外，我们可以证明位于第8、9和10号染色体上的拷贝数丢失对前列腺癌的侵袭性有显着影响（P = 0.040，P = 0.037和P = 0.005）。应用交叉验证分析得出的曲线下面积为0.63。我们的研究报告了令人鼓舞的发现，表明拷贝数丢失可能在建立新型生物标志物以预测诊断时预测前列腺癌侵袭性中发挥重要作用。此类标记物可用于促进风险分层，以减少对前列腺癌患者的过度治疗。