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Magnetic resonance metabolic profiling of estrogen receptor-positive breast cancer: correlation with currently used molecular markers.

ABSTRACT: Estrogen receptor (ER)-positive breast cancers overall have a good prognosis, however, some patients suffer relapses and do not respond to endocrine therapy. The purpose of this study was to determine whether there are any correlations between high-resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) metabolic profiles of core needle biopsy (CNB) specimens and the molecular markers currently used in patients with ER-positive breast cancers. The metabolic profiling of CNB samples from 62 ER-positive cancers was performed by HR-MAS MRS. Metabolic profiles were compared according to human epidermal growth factor receptor 2 (HER2) and Ki-67 status, and luminal type, using the Mann-Whitney test. Multivariate analysis was performed with orthogonal projections to latent structure-discriminant analysis (OPLS-DA). In univariate analysis, the HER2-positive group was shown to have higher levels of glycine and glutamate, compared to the HER2-negative group (P<0.01, and P <0.01, respectively). The high Ki-67 group showed higher levels of glutamate than the low Ki-67 group without statistical significance. Luminal B cancers showed higher levels of glycine (P=0.01) than luminal A cancers. In multivariate analysis, the OPLS-DA models built with HR-MAS MR metabolic profiles showed visible discrimination between the subgroups according to HER2 and Ki-67 status, and luminal type. This study showed that the metabolic profiles of CNB samples assessed by HR-MAS MRS can be used to detect potential prognostic biomarkers as well as to understand the difference in metabolic mechanism among subtypes of ER-positive breast cancer.

SUBMITTER: Choi JS

PROVIDER: S-EPMC5609932 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Visceral adipose tissue (VAT) plays an important role in the pathogenesis of insulin resistance (IR), prediabetes and type 2 diabetes. However, VAT volume alone might not be the best marker for insulin resistance and prediabetes or diabetes, as a given VAT volume may impact differently on these metabolic traits based on body height, gender, age and ethnicity. In a cohort of 1295 subjects from the Tübingen Diabetes Family Study (TDFS) and in 9978 subjects from the UK Biobank (UKBB) undergoing magnetic resonance imaging for quantification of VAT volume, total adipose tissue (TAT) in the TDFS, total abdominal adipose tissue (TAAT) in the UKBB, and total lean tissue (TLT), VAT volume and several VAT-indices were investigated for their relationships with insulin resistance and glycemic traits. VAT-related indices were calculated by correcting for body height (VAT/m:VAT/body height; VAT/m2:VAT/(body height)2, and VAT/m3:VAT/(body height)3), TAT (%VAT), TLT (VAT/TLT) and weight (VAT/WEI), with closest equivalents used within the UKBB dataset. Prognostic values of VAT and VAT-related indices for insulin sensitivity, HbA1c levels and prediabetes/diabetes were analyzed for males and females. Males had higher VAT volume and VAT-related indices than females in both cohorts (p < 0.0001) and VAT volume has shown to be a stronger determinant for insulin sensitivity than anthropometric variables. Among the parameters uncorrected VAT and derived indices, VAT/m3 most strongly correlated negatively with insulin sensitivity and positively with HbA1c levels and prediabetes/diabetes in the TDFS (R2 = 0.375/0.305 for females/males for insulin sensitivity, 0.178/0.148 for HbA1c levels vs., e.g., 0..355/0.293 and 0.144/0.133 for VAT, respectively) and positively with HbA1c (R2 = 0.046/0.042) in the UKBB for females and males. Furthermore, VAT/m3 was found to be a significantly better determinant of insulin resistance or prediabetes than uncorrected VAT volume (p < 0.001/0.019 for females/males regarding insulin sensitivity, p < 0.001/< 0.001 for females/males regarding HbA1c).Evaluation of several indices derived from VAT volume identified VAT/m3 to correlate most strongly with insulin sensitivity and glucose metabolism. Thus, VAT/m3 appears to provide better indications of metabolic characteristics (insulin sensitivity and pre-diabetes/diabetes) than VAT volume alone.

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Magnetic resonance metabolic profiling of estrogen receptor-positive breast cancer: correlation with currently used molecular markers.

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