Nejc Kozar1, Kristi Kruusmaa2, Marko Bitenc3, Rosa Argamasilla3, Antonio Adsuar3, Iztok Takač4, Darja Arko4. 1. Division of Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia. Electronic address: nejc@kozar.me. 2. Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia; Universal Diagnostics, S.L. Centre of Research Technology and Innovation, University of Seville, Seville, Spain. 3. Universal Diagnostics, S.L. Centre of Research Technology and Innovation, University of Seville, Seville, Spain. 4. Division of Gynaecology and Perinatology, University Medical Centre Maribor, Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Abstract
INTRODUCTION: Breast cancer (BC) is the most common cancer in women, with a high disease burden, especially in the advanced disease stages. Our study investigated the metabolomic profile of breast cancer patients' serum with the aim of identifying novel diagnostic biomarkers that could be used, especially for early disease detection. MATERIALS AND METHODS: Using targeted metabolomic serum profiling based on high-performance liquid chromatography mass spectrometry, women with BC (n = 39) and a control group (n = 21) were examined for 232 endogenous metabolites. RESULTS: The top performing biomarkers included acylcarnitines (ACs) and 9,12-linoleic acid. A combined panel of the top 4 biomarkers achieved 83% sensitivity and 81% specificity, with an area under the curve (AUC) of 0.839 (95% confidence interval, 0.811-0.867). Individual markers also provided significant predictive values: AC 12:0, sensitivity of 72%, specificity of 67%, and AUC of 0.71; AC 14:2, sensitivity of 74%, specificity of 71%, and AUC of 0.73; AC 14:0: sensitivity of 67%, specificity of 81%, and AUC of 0.73; and 9,12-linoleic acid, sensitivity of 69%, specificity of 67%, and AUC of 0.71. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. CONCLUSION: Using mass spectrometry-targeted metabolomic profiling, ACs and 9,12-linoleic acid were identified as potential diagnostic biomarkers for breast cancer. Additionally, these identified metabolites could provide additional insight into cancer cell metabolism.
INTRODUCTION: Breast cancer (BC) is the most common cancer in women, with a high disease burden, especially in the advanced disease stages. Our study investigated the metabolomic profile of breast cancer patients' serum with the aim of identifying novel diagnostic biomarkers that could be used, especially for early disease detection. MATERIALS AND METHODS: Using targeted metabolomic serum profiling based on high-performance liquid chromatography mass spectrometry, women with BC (n = 39) and a control group (n = 21) were examined for 232 endogenous metabolites. RESULTS: The top performing biomarkers included acylcarnitines (ACs) and 9,12-linoleic acid. A combined panel of the top 4 biomarkers achieved 83% sensitivity and 81% specificity, with an area under the curve (AUC) of 0.839 (95% confidence interval, 0.811-0.867). Individual markers also provided significant predictive values: AC 12:0, sensitivity of 72%, specificity of 67%, and AUC of 0.71; AC 14:2, sensitivity of 74%, specificity of 71%, and AUC of 0.73; AC 14:0: sensitivity of 67%, specificity of 81%, and AUC of 0.73; and 9,12-linoleic acid, sensitivity of 69%, specificity of 67%, and AUC of 0.71. The individual markers, however, did not reach the high sensitivity and specificity of the 4-biomarker combination. CONCLUSION: Using mass spectrometry-targeted metabolomic profiling, ACs and 9,12-linoleic acid were identified as potential diagnostic biomarkers for breast cancer. Additionally, these identified metabolites could provide additional insight into cancer cell metabolism.
Authors: Judith Buentzel; Henry Gerd Klemp; Ralph Kraetzner; Matthias Schulz; Gry Helene Dihazi; Frank Streit; Annalen Bleckmann; Kerstin Menck; Darius Wlochowitz; Claudia Binder Journal: Int J Mol Sci Date: 2021-12-17 Impact factor: 5.923