Plasmalogen Deficiency and Overactive Fatty Acid Elongation Biomarkers in Serum of Breast Cancer Patients Pre- and Post-Surgery—New Insights on Diagnosis, Risk Assessment, and Disease Mechanisms
| Autor: | Satomi Tomida, Dayan B. Goodenowe, Ritei Uehara, Koichi Sakaguchi, Tetsuya Taguchi, Midori Morita, Etsuko Ozaki, Nagato Kuriyama, Teruhide Koyama, Yasuyo Yamazaki |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Cancer Research
medicine.medical_specialty Plasmalogen Linoleic acid Blood lipids plasmalogen Article chemistry.chemical_compound Breast cancer breast cancer Internal medicine medicine RC254-282 chemistry.chemical_classification Fatty acid Neoplasms. Tumors. Oncology. Including cancer and carcinogens ELOVL5 medicine.disease Endocrinology Oncology chemistry Docosahexaenoic acid Fatty acid elongation lipids (amino acids peptides and proteins) fatty acid Polyunsaturated fatty acid |
| Zdroj: | Cancers Volume 13 Issue 16 Cancers, Vol 13, Iss 4170, p 4170 (2021) |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers13164170 |
| Popis: | The polyunsaturated fatty acid (PUFA) elongase, ELOVL5, is upregulated in breast cancer (BC) vs. adjacent normal tissue. We performed a comprehensive lipid metabolomic analysis of serum using high-resolution accurate mass spectrometry from two case-control studies that included non-BC, BC subjects pre-surgery, and BC subjects one-month post-surgery to determine if the metabolic signatures of over-active fatty acid elongation and other lipid changes could be detected in BC vs. non-BC subjects: study 1 (n = 48: non-BC, n = 69: pre-surgery BC) study 2 (blinded validation: n = 121: non-BC, n = 62: pre-surgery BC, n = 31: one month post-surgery). The ratio of the ELOVL5 precursor, linoleic acid (18:2) to a non-ELOVL5 precursor, oleic acid (18:1) was evaluated in multiple lipid pools (phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), lyso-PtdCho, and free fatty acids). This ratio was lower in pre-surgery BC subjects in all pools in both studies (p < 0.001). At one-month post-surgery, the 18:2/18:1 ratios increased vs. pre-surgery and were no longer different from non-BC subjects (p > 0.05 expect for lyso-PtdCho). In contrast to the elongation biomarkers, docosahexaenoic acid (22:6n-3) containing ethanolamine plasmalogen (EtnPls) species were observed to be further decreased in BC subjects one-month post-surgery vs. pre-surgery levels (p < 0.001). These results are consistent with the hypothesis that ELOVL5 is upregulated in BC tissue, which would result in the selective depletion of 18:2 vs. 18:1 containing lipid species. Surgical removal of the tumor removes the overactive ELOVL5 effect on serum lipids. In contrast, the low EtnPls levels do not appear to be caused by BC tumor activity and may be pre-existent and a possible risk factor for BC. These results indicate that it may be possible to screen for both breast cancer risk and breast cancer activity using a simple blood test. |
| Databáze: | OpenAIRE |
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