| 1. |
- Brockmöller, Scarlet F., et al.
(författare)
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Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling
- 2012
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 11:2, s. 850-60
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Tidskriftsartikel (refereegranskat)abstract
- Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.
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| 2. |
- Budczies, Jan, et al.
(författare)
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Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study
- 2012
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.CONCLUSIONS: For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.
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| 3. |
- Denkert, Carsten, et al.
(författare)
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Metabolomics of human breast cancer : new approaches for tumor typing and biomarker discovery
- 2012
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Ingår i: Genome Medicine. - London, United Kingdom : BioMed Central (BMC). - 1756-994X. ; 4:4
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Forskningsöversikt (refereegranskat)abstract
- Breast cancer is the most common cancer in women worldwide, and the development of new technologies for better understanding of the molecular changes involved in breast cancer progression is essential. Metabolic changes precede overt phenotypic changes, because cellular regulation ultimately affects the use of small-molecule substrates for cell division, growth or environmental changes such as hypoxia. Differences in metabolism between normal cells and cancer cells have been identified. Because small alterations in enzyme concentrations or activities can cause large changes in overall metabolite levels, the metabolome can be regarded as the amplified output of a biological system. The metabolome coverage in human breast cancer tissues can be maximized by combining different technologies for metabolic profiling. Researchers are investigating alterations in the steady state concentrations of metabolites that reflect amplified changes in genetic control of metabolism. Metabolomic results can be used to classify breast cancer on the basis of tumor biology, to identify new prognostic and predictive markers and to discover new targets for future therapeutic interventions. Here, we examine recent results, including those from the European FP7 project METAcancer consortium, that show that integrated metabolomic analyses can provide information on the stage, subtype and grade of breast tumors and give mechanistic insights. We predict an intensified use of metabolomic screens in clinical and preclinical studies focusing on the onset and progression of tumor development.
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| 4. |
- Edsjö, Anders, et al.
(författare)
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Precision cancer medicine : Concepts, current practice, and future developments
- 2023
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Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 294:4, s. 455-481
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Forskningsöversikt (refereegranskat)abstract
- Precision cancer medicine is a multidisciplinary team effort that requires involvement and commitment of many stakeholders including the society at large. Building on the success of significant advances in precision therapy for oncological patients over the last two decades, future developments will be significantly shaped by improvements in scalable molecular diagnostics in which increasingly complex multilayered datasets require transformation into clinically useful information guiding patient management at fast turnaround times. Adaptive profiling strategies involving tissue- and liquid-based testing that account for the immense plasticity of cancer during the patient's journey and also include early detection approaches are already finding their way into clinical routine and will become paramount. A second major driver is the development of smart clinical trials and trial concepts which, complemented by real-world evidence, rapidly broaden the spectrum of therapeutic options. Tight coordination with regulatory agencies and health technology assessment bodies is crucial in this context. Multicentric networks operating nationally and internationally are key in implementing precision oncology in clinical practice and support developing and improving the ecosystem and framework needed to turn invocation into benefits for patients. The review provides an overview of the diagnostic tools, innovative clinical studies, and collaborative efforts needed to realize precision cancer medicine.
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