Metabolic clusters of breast cancer in relation to gene- and protein expression subtypes

Background: The heterogeneous biology of breast cancer leads to high diversity in prognosis and response to treatment, even for patients with similar clinical diagnosis, histology, and stage of disease. Identifying mechanisms contributing to this heterogeneity may reveal new cancer targets or clinically relevant subgroups for treatment stratification. In this study, we have merged metabolite, protein, and gene expression data from breast cancer patients to examine the heterogeneity at a molecular level.Methods: The study included primary tumor samples from 228 non-treated breast cancer patients. High-resolution magic-angle spinning magnetic resonance spectroscopy (HR MAS MRS) was performed to extract the tumors metabolic profiles further used for hierarchical cluster analysis resulting in three significantly different metabolic clusters (Mc1, Mc2, and Mc3). The clusters were further combined with gene and protein expression data.Results: Our result revealed distinct differences in the metabolic profile of the three metabolic clusters. Among the most interesting differences, Mc1 had the highest levels of glycerophosphocholine (GPC) and phosphocholine (PCho), Mc2 had the highest levels of glucose, and Mc3 had the highest levels of lactate and alanine. Integrated pathway analysis of metabolite and gene expression data uncovered differences in glycolysis/gluconeogenesis and glycerophospholipid metabolism between the clusters. All three clusters had significant differences in the distribution of protein subtypes classified by the expression of breast cancer-related proteins. Genes related to collagens and extracellular matrix were downregulated in Mc1 and consequently upregulated in Mc2 and Mc3, underpinning the differences in protein subtypes within the metabolic clusters. Genetic subtypes were evenly distributed among the three metabolic clusters and could therefore contribute to additional explanation of breast cancer heterogeneity.Conclusions: Three naturally occurring metabolic clusters of breast cancer were detected among primary tumors from non-treated breast cancer patients. The clusters expressed differences in breast cancer-related protein as well as genes related to extracellular matrix and metabolic pathways known to be aberrant in cancer. Analyses of metabolic activity combined with gene and protein expression provide new information about the heterogeneity of breast tumors and, importantly, the metabolic differences infer that the clusters may be susceptible to different metabolically targeted drugs

Conflicting Values or Common Ground? : Some Concluding Thoughts

Peer reviewe

NMR-Based Prostate Cancer Metabolomics

Author's accepted version (postprint).This is an Accepted Manuscript of an article published by Springer in Methods in Molecular Biology on 22 May 2018.Available online: https://doi.org/10.1007/978-1-4939-7845-8_14acceptedVersio

A Randomized Controlled Trial Comparing the Attention Training Technique and Mindful Self-Compassion for Students With Symptoms of Depression and Anxiety

The Attention Training Technique (ATT) and Mindful Self-Compassion (MSC) are two promising psychological interventions. ATT is a 12-min auditory exercise designed to strengthen attentional control and promote external focus of attention, while MSC uses guided meditation and exercises designed to promote self-compassion. In this randomized controlled trial (RCT), a three-session intervention trial was conducted in which university students were randomly assigned to either an ATT-group (n = 40) or a MSC-group (n = 41). The students were not assessed with diagnostic interviews but had self-reported symptoms of depression, anxiety, or stress. Participants listened to audiotapes of ATT or MSC before discussing in groups how to apply these principles for their everyday struggles. Participants also listened to audiotapes of ATT and MSC as homework between sessions. Participants in both groups showed significant reductions in symptoms of anxiety and depression accompanied by significant increases in mindfulness, self-compassion, and attention flexibility post-intervention. These results were maintained at 6-month follow-up. Improvement in attention flexibility was the only significant unique predictor of treatment response. The study supports the use of both ATT and MSC for students with symptoms of depression and anxiety. Further, it suggests that symptom improvement is related to changes in attention flexibility across both theoretical frameworks. Future studies should focus on how to strengthen the ability for attention flexibility to optimize treatment for emotional disorder

A Randomized Controlled Trial Comparing the Attention Training Technique and Mindful Self-Compassion for Students With Symptoms of Depression and Anxiety

The Attention Training Technique (ATT) and Mindful Self-Compassion (MSC) are two promising psychological interventions. ATT is a 12-min auditory exercise designed to strengthen attentional control and promote external focus of attention, while MSC uses guided meditation and exercises designed to promote self-compassion. In this randomized controlled trial (RCT), a three-session intervention trial was conducted in which university students were randomly assigned to either an ATT-group (n = 40) or a MSC-group (n = 41). The students were not assessed with diagnostic interviews but had self-reported symptoms of depression, anxiety, or stress. Participants listened to audiotapes of ATT or MSC before discussing in groups how to apply these principles for their everyday struggles. Participants also listened to audiotapes of ATT and MSC as homework between sessions. Participants in both groups showed significant reductions in symptoms of anxiety and depression accompanied by significant increases in mindfulness, self-compassion, and attention flexibility post-intervention. These results were maintained at 6-month follow-up. Improvement in attention flexibility was the only significant unique predictor of treatment response. The study supports the use of both ATT and MSC for students with symptoms of depression and anxiety. Further, it suggests that symptom improvement is related to changes in attention flexibility across both theoretical frameworks. Future studies should focus on how to strengthen the ability for attention flexibility to optimize treatment for emotional disorder