Protein and lipid MALDI profiles classify breast cancers according to the intrinsic subtype.
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.
National Cancer Center, Goyang, 410-769, Korea.
Han Sung
HS
Kang
Seok Cheol
SC
Lee
Young Seung
YS
Park
Young Eun
YE
Jeon
Jeong Hwa
JH
Lee
So-Youn
SY
Jung
In Hae
IH
Park
Seok Hoon
SH
Jang
Hye Min
HM
Park
Chong Woo
CW
Yoo
Seok Hee
SH
Park
Sang Yun
SY
Han
Kwang Pyo
KP
Kim
Young Hwan
YH
Kim
Jungsil
J
Ro
Hark Kyun
HK
Kim
D000230:Adenocarcinoma / Q000145:classification* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000145:classification* / Q000378:metabolism; D002277:Carcinoma / Q000145:classification* / Q000378:metabolism; D005260:Female; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D012189:Retrospective Studies; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
D008055:Lipids; D009363:Neoplasm Proteins