Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii.
Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee.
Cancer Res. 2019 Sep 15;79(18):4592-4598. doi: 10.1158/0008-5472.CAN-18-3997. Epub 2019 Jul 23.
Several blood protein biomarkers have been associated with prostate cancer risk. However, most studies assessed only a small number of biomarkers and/or included a small sample size. To identify novel protein biomarkers of prostate cancer risk, we studied 79,194 cases and 61,112 controls of European ancestry, included in the PRACTICAL/ELLIPSE consortia, using genetic instruments of protein quantitative trait loci for 1,478 plasma proteins. A total of 31 proteins were associated with prostate cancer risk including proteins encoded by , whose methylation level was shown previously to be associated with prostate cancer risk, and , and , which were previously implicated as potential target genes of prostate cancer risk variants identified in genome-wide association studies. A total of 18 proteins inversely correlated and 13 positively correlated with prostate cancer risk. For 28 of the identified proteins, gene somatic changes of short indels, splice site, nonsense, or missense mutations were detected in patients with prostate cancer in The Cancer Genome Atlas. Pathway enrichment analysis showed that relevant genes were significantly enriched in cancer-related pathways. In conclusion, this study identifies 31 candidates of protein biomarkers for prostate cancer risk and provides new insights into the biology and genetics of prostate tumorigenesis. SIGNIFICANCE: Integration of genomics and proteomics data identifies biomarkers associated with prostate cancer risk.
已有多种血液蛋白生物标志物与前列腺癌风险相关。然而，大多数研究仅评估了少数几种生物标志物，或纳入的样本量较小。为了鉴定前列腺癌风险的新型蛋白生物标志物，我们使用了 1478 种血浆蛋白的蛋白定量性状的遗传工具，对欧洲血统的 79194 例病例和 61112 例对照进行了研究，这些病例和对照纳入了 PRACTICAL/ELLIPSE 联盟。共有 31 种蛋白与前列腺癌风险相关，包括先前已证实与前列腺癌风险相关的蛋白编码基因 ，以及先前被认为是全基因组关联研究中发现的前列腺癌风险变异的潜在靶基因的蛋白编码基因 ， 和 。共有 18 种蛋白与前列腺癌风险呈负相关，13 种蛋白与前列腺癌风险呈正相关。在癌症基因组图谱中，在前列腺癌患者中检测到了所鉴定的 28 种蛋白中，有短插入/缺失、剪接位点、无义或错义突变的基因体细胞变化。途径富集分析显示，相关基因在癌症相关途径中显著富集。总之，本研究鉴定了 31 种与前列腺癌风险相关的蛋白生物标志物候选物，为前列腺肿瘤发生的生物学和遗传学提供了新的见解。
基因组学和蛋白质组学数据的整合鉴定出了与前列腺癌风险相关的生物标志物。
