Goto Takayuki, Terada Naoki, Inoue Takahiro, Nakayama Kenji, Okada Yoshiyuki, Yoshikawa Takeshi, Miyazaki Yu, Uegaki Masayuki, Sumiyoshi Shinji, Kobayashi Takashi, Kamba Tomomi, Yoshimura Koji, Ogawa Osamu
Department of Urology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
PLoS One. 2014 Feb 28;9(2):e90242. doi: 10.1371/journal.pone.0090242. eCollection 2014.
High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT) compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS) showed that these molecules included 14 phosphatidylinositols (PIs), 3 phosphatidylethanolamines (PEs) and 3 phosphatidic acids (PAs). Among the PIs, the expression of PI(18:0/18:1), PI(18:0/20:3) and PI(18:0/20:2) were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA). The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.
高分辨率基质辅助激光解吸/电离成像质谱(HR-MALDI-IMS)是一种新兴的应用技术,用于在组织切片上原位全面、详细地分析离子化分子的空间分布。对在根治性前列腺切除术时从前列腺癌患者获取的、包埋于最佳切割温度(OCT)复合物中的人类前列腺组织样本,在m/z 500-1000质量范围内以负模式进行HR-MALDI-IMS分析。对发现集中的14个样本进行HR-MALDI-IMS分析,确定了26种在前列腺中高表达的分子。串联质谱(MS/MS)显示这些分子包括14种磷脂酰肌醇(PI)、3种磷脂酰乙醇胺(PE)和3种磷脂酸(PA)。在PI中,PI(18:0/18:1)、PI(18:0/20:3)和PI(18:0/20:2)在癌组织中的表达显著高于良性上皮组织。通过使用正交偏最小二乘判别分析(OPLS-DA)分析发现集中癌组织和良性上皮组织中PI的表达谱,制定了一种前列腺癌生物标志物算法。该算法在24个验证集样本中对前列腺癌诊断的敏感性和特异性分别为87.5%和91.7%。总之,HR-MALDI-IMS确定了几种PI在前列腺癌中的表达高于良性前列腺上皮组织。PI表达谱的这些差异可能成为前列腺癌的一种新型诊断工具。