Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer
Metabolic Profiling of Formalin-Fixed Paraffin-Embedded Tissues Discriminates Normal Colon from Colorectal Cancer
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DOI：
10.1158/1541-7786.mcr-19-1091
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发表时间：
2020-06-01
影响因子：
5.2
通讯作者：
Ogino, Shuji
中科院分区：
文献类型：
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作者：
Arima, Kota;Lau, Mai Chan;Ogino, Shuji
越来越多的证据表明，代谢重编程在癌症发生和肿瘤进展中具有关键作用。与新鲜冷冻组织材料相比，福尔马林固定石蜡包埋（FFPE）组织材料用于代谢组学分析的有用性仍不清楚。对结直肠癌患者FFPE和新鲜冷冻组织材料中的11对匹配的肿瘤和正常组织进行基于LC/MS-MS的代谢组学分析。采用排列t检验鉴别肿瘤组织和正常组织中丰度差异较大的代谢物。在FFPE样品中共检测到200种代谢物，在新鲜冷冻样品中共检测到536种代谢物。FFPE样品中代谢物的保存根据类别和化学特征而不同，范围从78%（能量）到0%（肽）。与正常组织相比，来自FFPE和新鲜冷冻样本的肿瘤组织中分别积累或消耗了34种（17%）和174种（32%）代谢物。其中，15种代谢产物在FFPE和新鲜冷冻样品中均常见。值得注意的是，支链氨基酸在肿瘤组织中高度积累。使用KEGG途径分析，乙醛酸和二羧酸代谢，精氨酸和脯氨酸，甘油磷脂，甘氨酸，丝氨酸和苏氨酸代谢途径区分肿瘤与正常组织中发现FFPE和新鲜冷冻样品。本研究表明，可以从FFPE组织材料中检索代谢谱的信息数据。
Accumulating evidence suggests that metabolic reprogramming has a critical role in carcinogenesis and tumor progression. The usefulness of formalin-fixed paraffin-embedded (FFPE) tissue material for metabolomics analysis as compared with fresh frozen tissue material remains unclear. LC/MS-MS-based metabolomics analysis was performed on 11 pairs of matched tumor and normal tissues in both FFPE and fresh frozen tissue materials from patients with colorectal carcinoma. Permutation t test was applied to identify metabolites with differential abundance between tumor and normal tissues. A total of 200 metabolites were detected in the FFPE samples and 536 in the fresh frozen samples. The preservation of metabolites in FFPE samples was diverse according to classes and chemical characteristics, ranging from 78% (energy) to 0% (peptides). Compared with the normal tissues, 34 (17%) and 174 (32%) metabolites were either accumulated or depleted in the tumor tissues derived from FFPE and fresh frozen samples, respectively. Among them, 15 metabolites were common in both FFPE and fresh frozen samples. Notably, branched chain amino acids were highly accumulated in tumor tissues. Using KEGG pathway analyses, glyoxylate and dicarboxylate metabolism, arginine and proline, glycerophospholipid, and glycine, serine, and threonine metabolism pathways distinguishing tumor from normal tissues were found in both FFPE and fresh frozen samples. This study demonstrates that informative data of metabolic profiles can be retrieved from FFPE tissue materials.