Cacciatore Stefano, Zadra Giorgia, Bango Clyde, Penney Kathryn L, Tyekucheva Svitlana, Yanes Oscar, Loda Massimo
Department of Medical Oncology, Center of Molecular Oncologic Pathology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
Mol Cancer Res. 2017 Apr;15(4):439-447. doi: 10.1158/1541-7786.MCR-16-0262. Epub 2017 Jan 10.
Metabolite profiling has significantly contributed to a deeper understanding of the biochemical metabolic networks and pathways in cancer cells. Metabolomics-based biomarker discovery would greatly benefit from the ability to interrogate retrospective annotated clinical specimens archived as formalin-fixed, paraffin-embedded (FFPE) material. Mass spectrometry-based metabolomic analysis was performed in matched frozen and FFPE human prostate cancers as well as isogenic prostate cancer cell lines. A total of 352 and 460 metabolites were profiled in human tissues and cell lines, respectively. Classes and physical-chemical characteristics of the metabolites preserved in FFPE material were characterized and related to their preservation or loss following fixation and embedding. Metabolite classes were differentially preserved in archival FFPE tissues, regardless of the age of the block, compared with matched frozen specimen, ranging from maximal preservation of fatty acids (78%) to loss of the majority of peptides and steroids. Generally, FFPE samples showed a decrease of metabolites with functional groups, such as carboxamide. As an adjunct technique, metabolic profiles were also obtained from FFPE tissue sections where metabolites were extracted in a manner that preserves tissue architecture. Despite the fact that selected metabolites were not retained after processing, global metabolic profiles obtained from FFPE can be used to predict biologic states and study biologic pathways. These results pave the way for metabolomics-based biomarker discovery/validation utilizing retrospective and clinically annotated FFPE collections. Metabolic profiles can be performed in archival tissue and may be used to complement other profiling methods such as gene expression for biomarker discovery or pathway analysis in the assessment of biologic states. .
代谢物谱分析对于深入了解癌细胞中的生化代谢网络和途径做出了重大贡献。基于代谢组学的生物标志物发现将极大地受益于对以福尔马林固定、石蜡包埋（FFPE）材料存档的回顾性注释临床标本进行检测的能力。在匹配的冷冻和FFPE人类前列腺癌以及同基因前列腺癌细胞系中进行了基于质谱的代谢组学分析。在人体组织和细胞系中分别分析了总共352种和460种代谢物。对FFPE材料中保存的代谢物的类别和物理化学特征进行了表征，并将其与固定和包埋后它们的保存或损失情况相关联。与匹配的冷冻标本相比，无论组织块的年代如何，代谢物类别在存档的FFPE组织中的保存情况存在差异，从脂肪酸的最大保存率（78%）到大多数肽和类固醇的损失不等。一般来说，FFPE样本中具有官能团的代谢物（如羧酰胺）有所减少。作为一种辅助技术，还从FFPE组织切片中获得了代谢谱，其中代谢物的提取方式保留了组织结构。尽管在处理后选定的代谢物没有保留下来，但从FFPE获得的整体代谢谱可用于预测生物学状态和研究生物学途径。这些结果为利用回顾性和临床注释的FFPE样本进行基于代谢组学的生物标志物发现/验证铺平了道路。代谢谱分析可以在存档组织中进行，并可用于补充其他分析方法，如用于生物标志物发现的基因表达分析或评估生物学状态时的途径分析。
