Takakura Michiko, Yokomizo Akira, Tanaka Yoshinori, Kobayashi Michimoto, Jung Giman, Banno Miho, Sakuma Tomohiro, Imada Kenjiro, Oda Yoshinao, Kamita Masahiro, Honda Kazufumi, Yamada Tesshi, Naito Seiji, Ono Masaya
Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
ISRN Oncol. 2012;2012:768190. doi: 10.5402/2012/768190. Epub 2012 Nov 19.
Serum prostate-specific antigen (PSA) levels ranging from 4 to 10 ng/mL is considered a diagnostic gray zone for detecting prostate cancer because biopsies reveal no evidence of cancer in 75% of these subjects. Our goal was to discover a new highly specific biomarker for prostate cancer by analyzing plasma proteins using a proteomic technique. Enriched plasma proteins from 25 prostate cancer patients and 15 healthy controls were analyzed using a label-free quantitative shotgun proteomics platform called 2DICAL (2-dimensional image converted analysis of liquid chromatography and mass spectrometry) and candidate biomarkers were searched. Among the 40,678 identified mass spectrum (MS) peaks, 117 peaks significantly differed between prostate cancer patients and healthy controls. Ten peaks matched carbonic anhydrase I (CAI) by tandem MS. Independent immunological assays revealed that plasma CAI levels in 54 prostate cancer patients were significantly higher than those in 60 healthy controls (P = 0.022, Mann-Whitney U test). In the PSA gray-zone group, the discrimination rate of prostate cancer patients increased by considering plasma CAI levels. CAI can potentially serve as a valuable plasma biomarker and the combination of PSA and CAI may have great advantages for diagnosing prostate cancer in patients with gray-zone PSA level.
血清前列腺特异性抗原（PSA）水平在4至10 ng/mL之间被认为是检测前列腺癌的诊断灰色区域，因为在这些受试者中，75%的活检未发现癌症证据。我们的目标是通过使用蛋白质组学技术分析血浆蛋白来发现一种新的高度特异性前列腺癌生物标志物。使用一种名为2DICAL（二维图像转换液相色谱和质谱分析）的无标记定量鸟枪法蛋白质组学平台分析了25例前列腺癌患者和15例健康对照者的富集血浆蛋白，并寻找候选生物标志物。在40678个鉴定出的质谱峰中，117个峰在前列腺癌患者和健康对照者之间有显著差异。通过串联质谱，10个峰与碳酸酐酶I（CAI）匹配。独立免疫分析显示，54例前列腺癌患者的血浆CAI水平显著高于60例健康对照者（P = 0.022，曼-惠特尼U检验）。在PSA灰色区域组中，考虑血浆CAI水平可提高前列腺癌患者的诊断率。CAI有可能作为一种有价值的血浆生物标志物，PSA和CAI的联合应用可能在诊断PSA水平处于灰色区域的患者的前列腺癌方面具有很大优势。
