TY - JOUR
T1 - Triple Negative Breast Cancer Detection Using LC-MS/MS Lipidomic Profiling
AU - Eghlimi, Ryan
AU - Shi, Xiaojian
AU - Hrovat, Jonathan
AU - Xi, Bowei
AU - Gu, Haiwei
N1 - Funding Information:
This study is supported by the College of Health Solutions, Arizona State University, and Brander Beacons Cancer Research. The help from Paniz Jasbi on data analysis and paper writing is also greatly appreciated.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/6/5
Y1 - 2020/6/5
N2 - Breast cancer (BC) is a heterogeneous malignancy that is responsible for a great portion of female cancer cases and cancer-related deaths in the United States. In comparison to other major BC subtypes, triple negative breast cancer (TNBC) presents with a relatively low survival rate and a high rate of metastasis. This has led to a strong, though largely unmet, need for more sensitive and specific methods of early-stage TNBC (ES-TNBC) detection to combat its high-grade pathology and relatively low survival rate. The current study employs a liquid chromatography-tandem mass spectrometry assay capable of targeted, highly specific, and sensitive detection of lipids to propose two diagnostic biomarker panels for TNBC/ES-TNBC. Using this approach, 110 lipids were reliably detected in 166 human plasma samples, 45 controls, and 121 BC (96 non-TNBC and 25 TNBC) subjects. Univariate and multivariate analyses allowed the construction and application of a 19-lipid biomarker panel capable of distinguishing TNBC (and ES-TNBC) from controls, as well as a 5-lipid biomarker panel capable of differentiating TNBC from non-TNBC and ES-TNBC from ES-non-TNBC. Receiver operating characteristic curves with notable classification performances were generated from the biomarker panels according to their orthogonal partial least-squares discrimination analysis models. TNBC was distinguished from controls with an area under the receiving operating characteristic curve (AUROC) = 0.93, sensitivity = 0.96, and specificity = 0.76 and ES-TNBC from controls with an AUROC = 0.96, sensitivity = 0.95, and specificity = 0.89. TNBC was differentiated from non-TNBC with an AUROC = 0.88, sensitivity = 0.88, and specificity = 0.79 and ES-TNBC from ES-non-TNBC with an AUROC = 0.95, sensitivity = 0.95, and specificity = 0.87. A pathway enrichment analysis between TNBC and controls also revealed significant disturbances in choline metabolism, sphingolipid signaling, and glycerophospholipid metabolism. To the best of our knowledge, this is the first study to propose a diagnostic lipid biomarker panel for TNBC detection. All raw mass spectrometry data have been deposited to MassIVE (dataset identifier MSV000085324).
AB - Breast cancer (BC) is a heterogeneous malignancy that is responsible for a great portion of female cancer cases and cancer-related deaths in the United States. In comparison to other major BC subtypes, triple negative breast cancer (TNBC) presents with a relatively low survival rate and a high rate of metastasis. This has led to a strong, though largely unmet, need for more sensitive and specific methods of early-stage TNBC (ES-TNBC) detection to combat its high-grade pathology and relatively low survival rate. The current study employs a liquid chromatography-tandem mass spectrometry assay capable of targeted, highly specific, and sensitive detection of lipids to propose two diagnostic biomarker panels for TNBC/ES-TNBC. Using this approach, 110 lipids were reliably detected in 166 human plasma samples, 45 controls, and 121 BC (96 non-TNBC and 25 TNBC) subjects. Univariate and multivariate analyses allowed the construction and application of a 19-lipid biomarker panel capable of distinguishing TNBC (and ES-TNBC) from controls, as well as a 5-lipid biomarker panel capable of differentiating TNBC from non-TNBC and ES-TNBC from ES-non-TNBC. Receiver operating characteristic curves with notable classification performances were generated from the biomarker panels according to their orthogonal partial least-squares discrimination analysis models. TNBC was distinguished from controls with an area under the receiving operating characteristic curve (AUROC) = 0.93, sensitivity = 0.96, and specificity = 0.76 and ES-TNBC from controls with an AUROC = 0.96, sensitivity = 0.95, and specificity = 0.89. TNBC was differentiated from non-TNBC with an AUROC = 0.88, sensitivity = 0.88, and specificity = 0.79 and ES-TNBC from ES-non-TNBC with an AUROC = 0.95, sensitivity = 0.95, and specificity = 0.87. A pathway enrichment analysis between TNBC and controls also revealed significant disturbances in choline metabolism, sphingolipid signaling, and glycerophospholipid metabolism. To the best of our knowledge, this is the first study to propose a diagnostic lipid biomarker panel for TNBC detection. All raw mass spectrometry data have been deposited to MassIVE (dataset identifier MSV000085324).
KW - LC-MS/MS
KW - biomarker discovery
KW - early diagnosis
KW - lipidomics
KW - triple negative breast cancer
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U2 - 10.1021/acs.jproteome.0c00038
DO - 10.1021/acs.jproteome.0c00038
M3 - Article
C2 - 32397718
AN - SCOPUS:85086481463
SN - 1535-3893
VL - 19
SP - 2367
EP - 2378
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 6
ER -