Author:
Kang Han Sung,Lee Seok Cheol,Park Young Seung,Jeon Young Eun,Lee Jeong Hwa,Jung So-Youn,Park In Hae,Jang Seok Hoon,Park Hye Min,Yoo Chong Woo,Park Seok Hee,Han Sang Yun,Kim Kwang Pyo,Kim Young Hwan,Ro Jungsil,Kim Hark Kyun
Abstract
Abstract
Background
Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of common solid tumors. Using recently developed MALDI matrices for lipid profiling, we evaluated whether direct tissue MALDI MS analysis on proteins and lipids may classify human breast cancer samples according to the intrinsic subtype.
Methods
Thirty-four pairs of frozen, resected breast cancer and adjacent normal tissue samples were analyzed using histology-directed, MALDI MS analysis. Sinapinic acid and 2,5-dihydroxybenzoic acid/α-cyano-4-hydroxycinnamic acid were manually deposited on areas of each tissue section enriched in epithelial cells to identify lipid profiles, and mass spectra were acquired using a MALDI-time of flight instrument.
Results
Protein and lipid profiles distinguish cancer from adjacent normal tissue samples with the median prediction accuracy of 94.1%. Luminal, HER2+, and triple-negative tumors demonstrated different protein and lipid profiles, as evidenced by permutation P values less than 0.01 for 0.632+ bootstrap cross-validated misclassification rates with all classifiers tested. Discriminatory proteins and lipids were useful for classifying tumors according to the intrinsic subtype with median prediction accuracies of 80.0-81.3% in random test sets.
Conclusions
Protein and lipid profiles accurately distinguish tumor from adjacent normal tissue and classify breast cancers according to the intrinsic subtype.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
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