Kim Il Chan, Bang Geul, Lee Jeong Hwa, Kim Kwang Pyo, Kim Young Hwan, Kim Hark Kyun, Chung Jinsoo
National Cancer Center, Goyang, Gyeonggi, 410-769, Korea.
J Mass Spectrom. 2014 May;49(5):409-16. doi: 10.1002/jms.3358.
Histopathologic diagnosis of renal cell carcinoma (RCC) may sometimes be difficult with small biopsy samples. We applied histology-directed matrix-assisted laser desorption/ionization mass spectrometry to RCC samples to evaluate whether and how lipid profiles are different between RCC and normal tissue. We evaluated 59 RCC samples and 24 adjacent normal tissue samples collected from patients who underwent surgery. Five peaks were significantly differently expressed (p < 10(-7)) between RCCs and adjacent normal tissue samples. C24-OH sulfatide (ST-OH {18:1/24:0}M-H; m/z 906.7 in the negative ion mode) and C22-OH sulfatide (ST-OH {18:1/22:0}M-H; m/z 878.6 in the negative ion mode) were most significantly underexpressed in RCC samples, compared with adjacent normal tissue samples. With 100 random training-to-test partitions within these samples, the median prediction accuracy (RCC vs. normal) ranged from 96.3% to 100% at p cutoff values for feature selection ranging from 0.001 to 10(-7). Two oncocytoma samples were predicted as normal tissue by five lipids that were differentially expressed between RCC and normal tissue at p < 10(-7). Clear-cell, papillary, and chromophobe RCCs were different in lipid profiles. Permutation p- values for 0.632+ bootstrap cross-validated misclassification rates were less than 0.05 for all the classifiers. Thus, lipid profiles differentiate RCC from normal tissue and may possibly classify the histology of RCC.
对于小活检样本,肾细胞癌(RCC)的组织病理学诊断有时可能会很困难。我们将组织学导向的基质辅助激光解吸/电离质谱技术应用于RCC样本,以评估RCC与正常组织之间的脂质谱是否以及如何不同。我们评估了59例RCC样本和24例从接受手术的患者身上采集的相邻正常组织样本。在RCC与相邻正常组织样本之间,有5个峰的表达存在显著差异(p < 10⁻⁷)。与相邻正常组织样本相比,C24 - OH硫苷脂(ST - OH {18:1/24:0}M - H;负离子模式下m/z 906.7)和C22 - OH硫苷脂(ST - OH {18:1/22:0}M - H;负离子模式下m/z 878.6)在RCC样本中表达最显著下调。在这些样本内进行100次随机训练 - 测试划分时,在特征选择的p截止值范围为0.001至10⁻⁷时,中位预测准确率(RCC与正常)在96.3%至100%之间。两个嗜酸细胞瘤样本被5种在RCC与正常组织之间差异表达(p < 10⁻⁷)的脂质预测为正常组织。透明细胞型、乳头状和嫌色细胞型RCC的脂质谱不同。对于所有分类器,0.632 + 自展交叉验证误分类率的排列p值均小于0.05。因此,脂质谱可区分RCC与正常组织,并且可能对RCC的组织学进行分类。