Correlated metabolomic, genomic, and histologic phenotypes in histologically normal breast tissue
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ABSTRACT:
PROVIDER: PRJNA437646 | ENA |
REPOSITORIES: ENA
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Project description:By the integrated analyses of histological, metabolomic and transcriptional data, we characterized two distinct subtypes of non-malignant breast tissue
2018-04-05 | GSE111601 | GEO
Project description:Breast carcinogenesis is a multistep process accompanied by widespread molecular and genomic alterations, both in tumor and in surrounding microenvironment. It is known that tumors have altered metabolism, but the metabolic changes in normal or cancer-adjacent, nonmalignant normal tissues and how these changes relate to alterations in gene expression and histological composition are not well understood. Normal or cancer-adjacent normal breast tissues from 99 women of the Normal Breast Study (NBS) were evaluated. Data of metabolomics, gene expression and histological composition was collected by mass spectrometry, whole genome microarray, and digital image, respectively. Unsupervised clustering analysis determined metabolomics-derived subtypes. Their association with genomic and histological features, as well as other breast cancer risk factors, genomic and histological features were evaluated using logistic regression. Unsupervised clustering of metabolites resulted in two main clusters. The metabolite differences between the two clusters suggested enrichment of pathways involved in lipid metabolism, cell growth and proliferation, and migration. Compared with Cluster 1, subjects in Cluster 2 were more likely to be obese (body mass index ≥30 kg/m2, p<0.05), have increased adipose proportion (p<0.01) and associated with a previously defined Active genomic subtype (p<0.01). By the integrated analyses of histological, metabolomics and transcriptional data, we characterized two distinct subtypes of non-malignant breast tissue. Further research is needed to validate our findings, and understand the potential role of these alternations in breast cancer initiation, progression and recurrence.
| S-EPMC5905995 | biostudies-literature
Project description:We have previously defined key metabolomic changes in Lung Squamous Cell Carcinoma (LSCC) compared to histologically normal tissues (Paes de Araújo et al., 2019). Here our goals were to define microRNA changes in the same tissues, in addition to verifying the detection of deregulated microRNAs in plasma from the same patients.
2023-07-08 | GSE149281 | GEO
Project description:Proliferation-correlated expression
| PRJNA580446 | ENA
Project description:Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers. Methods: We examined gene expression in 46 cases of microdissected NlEpi from previously untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 ER+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9ER+, 7 ER-), we validated seven selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results: 216 probes (corresponding to 198 unique genes) distinguished the NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers themselves, (e.g., ESR1, GATA3, and CX3CL1, FABP7, respectively). QPCR validated the microarray results in both a sampling of the 30 original cases (84%) and all of the 16 independent cases (77%). Gene expression in NlEpiER+ and NlEPIERNlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 36%-53% of the genes or probes examined in each the 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions: Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. Thus, breast cancer subtypes may be detectable before histologic abnormalities. NlEpi gene expression may help define subtype-specific risk signatures, identify initial subtype specific genomic differences, and suggest new targets for subtype-specific prevention and therapy. We determined that 216 probesets significantly differed between histologically normal epithelium from ER+ breast cancer patients and from ER- breast cancer patients, and that gene expression in each type of histologically normal epithelium resembles expression of the corresponding subtype of invasive breast cancer (i.e., ER+ or ER-). These findings suggest that characteristic features of breast cancer subtypes are detectable prior to any histologic abnormality. This suggestion has implications for understanding breast cancer biology and devising new tools for assessing breast cancer risk. 30 total laser capture microdissected histologically normal breast tissue samples were analyzed with Affymetrix HU133A microarrays. All samples were age-matched between histologically normal epithelial samples from ER+ breast cancer patients (n=15) and histologically normal epithelial samples from ER- breast cancer patients (n=15). Sample numbers correspond to individual patient samples. Of the 4 publicly available datasets mentioned above, the only dataset with a GEO number was GSE3494, corresponding to the Miller dataset. The supplementary file below lists the 251 Samples used from the GSE3494 study. We did not reanalyze the data - there was no change made to the Miller dataset; we only used these data for confirmation of our own dataset.
2010-12-07 | E-GEOD-21947 | biostudies-arrayexpress
Project description:Patients with Eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite remission. We aimed to characterize persisting molecular alterations in pediatric patients with EoE using tissue proteomics. Esophageal tissue biopsies (n=151) and clinical data were collected prospectively from pediatric patients with EoE (N=34), gastroesophageal reflux disease (GERD; N=10; inflammatory controls) or functional disorders (FD; N=20; non-inflammatory controls). Biospies (n=131) acquired from the diagnostic endoscopy and up to 7 follow-ups were considered for proteome analysis in patients with EoE, while for GERD and FD only biopsies from initial diagnosis were included. Histologically active EoE (15 eosinophils per high power field (hpf)) was diagnosed in 79 biopsies and 52 samples derived from patients with EoE in remission (15 eosinophils per hpf). After microdissection of the epithelium proteins were extracted from the esophageal tissue followed by a liquid chromatography-tandem mass spectrometry. Proteomic analysis identified 3,704 different proteins in total across all samples.
2024-09-23 | PXD052250 | Pride
Project description:Background: We hypothesize that important genomic differences between breast cancer subtypes occur early in carcinogenesis. Therefore, gene expression might distinguish histologically normal breast epithelium (NlEpi) from breasts containing estrogen receptor positive (ER+) compared with estrogen receptor negative (ER-) cancers. Methods: We examined gene expression in 46 cases of microdissected NlEpi from previously untreated women undergoing breast cancer surgery. From 30 age-matched cases (15 ER+, 15 ER-) we used Affymetryix U133A arrays. From 16 independent cases (9ER+, 7 ER-), we validated seven selected genes using qPCR. We then compared gene expression between NlEpi and invasive breast cancer using 4 publicly available datasets. Results: 216 probes (corresponding to 198 unique genes) distinguished the NlEpi from breasts with ER+ (NlEpiER+) compared to ER- cancers (NlEpiER-). These include genes characteristic of ER+ and ER- cancers themselves, (e.g., ESR1, GATA3, and CX3CL1, FABP7, respectively). QPCR validated the microarray results in both a sampling of the 30 original cases (84%) and all of the 16 independent cases (77%). Gene expression in NlEpiER+ and NlEPIERNlEpiER- resembled gene expression in ER+ and ER- cancers, respectively: 36%-53% of the genes or probes examined in each the 4 external datasets overlapped between NlEpi and the corresponding cancer subtype. Conclusions: Gene expression differs in NlEpi of breasts containing ER+ compared to ER- breast cancers. These differences echo differences in ER+ and ER- invasive cancers. Thus, breast cancer subtypes may be detectable before histologic abnormalities. NlEpi gene expression may help define subtype-specific risk signatures, identify initial subtype specific genomic differences, and suggest new targets for subtype-specific prevention and therapy. We determined that 216 probesets significantly differed between histologically normal epithelium from ER+ breast cancer patients and from ER- breast cancer patients, and that gene expression in each type of histologically normal epithelium resembles expression of the corresponding subtype of invasive breast cancer (i.e., ER+ or ER-). These findings suggest that characteristic features of breast cancer subtypes are detectable prior to any histologic abnormality. This suggestion has implications for understanding breast cancer biology and devising new tools for assessing breast cancer risk.
2010-12-07 | GSE21947 | GEO
Project description:Although multiple gene and protein expression have been extensively profiled in human pulmonary arterial hypertension (PAH), the mechanism for the development and progression of pulmonary hypertension remains elusive. Analysis of the global metabolomic heterogeneity within the pulmonary vascular system leads to a better understanding of disease progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung. The results suggest that PAH has specific metabolic pathways contributing to increased ATP synthesis for the vascular remodeling process in severe pulmonary hypertension. These identified metabolites may serve as potential biomarkers for the diagnosis of severe PAH. By profiling metabolomic alterations of the PAH lung, we reveal new pathogenic mechanisms of PAH in its later stage, which may differ from the earlier stage of PAH, opening an avenue of exploration for therapeutics that target metabolic pathway alterations in the progression of PAH. Global profiles were determined in human lung tissue and compared across 11 normal and 12 severe pulmonary arterial hypertension patients. Using a combination of microarray and high-throughput liquid-and-gas-chromatography-based mass spectrometry, we showed unbiased metabolomic profiles of disrupted glycolysis, increased TCA cycle, and fatty acid metabolites with altered oxidation pathways in the severe human PAH lung.
2014-11-14 | E-GEOD-53408 | biostudies-arrayexpress
Project description:To extend previous molecular analyses of rejection in liver transplant biopsies in the INTERLIVER study (ClinicalTrials.gov #NCT03193151), the present study aimed to define the gene expression selective for parenchymal injury, fibrosis, and steatohepatitis. PC1 reflected parenchymal injury and related inflammation in the early posttransplant period, slowly regressing over many months. PC2 separated early injury from late fibrosis. Positive PC3 identified a distinct mildly inflamed state correlating with histologic steatohepatitis. Injury PCs correlated with liver function and histologic abnormalities. A classifier trained on histologic steatohepatitis predicted histologic steatohepatitis with cross-validated AUC=0.83, and was associated with pathways reflecting metabolic abnormalities distinct from fibrosis. PC2 predicted histologic fibrosis (AUC=0.80), as did a molecular fibrosis classifier (AUC=0.74). The fibrosis classifier correlated with matrix remodeling pathways with minimal overlap with those selective for steatohepatitis, although some biopsies had both. Genome-wide assessment of liver transplant biopsies can not only detect molecular changes induced by rejection but also those correlating with parenchymal injury, steatohepatitis, and fibrosis, offering potential insights into disease mechanisms for primary diseases.
2022-01-09 | GSE193135 | GEO