Degradome/Peptidome Early-stage Breast Cancer
Ontology highlight
ABSTRACT:
INSTRUMENT(S): instrument model, LTQ, LTQ Orbitrap XL
ORGANISM(S): Homo Sapiens (human)
TISSUE(S): Blood Plasma
DISEASE(S): Carcinoma
SUBMITTER: 
Nikola Tolic
PROVIDER: PRD000185 | Pride | 2010-10-19
REPOSITORIES: Pride
Dataset's files
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Project description:BackgroundCancer invasion and metastasis are closely associated with activities within the degradome; however, little is known about whether these activities can be detected in the blood of cancer patients.Methodology and principal findingsThe peptidome-degradome profiles of pooled blood plasma sampled from 15 breast cancer patients (BCP) and age, race, and menopausal status matched control healthy persons (HP) were globally characterized using advanced comprehensive separations combined with tandem Fourier transform mass spectrometry and new data analysis approaches that facilitated top-down peptidomic analysis. The BCP pool displayed 71 degradome protein substrates that encompassed 839 distinct peptidome peptides. In contrast, the HP 50 degradome substrates found encompassed 425 peptides. We find that the ratios of the peptidome peptide relative abundances can vary as much as >4000 fold between BCP and HP. The experimental results also show differential degradation of substrates in the BCP sample in their functional domains, including the proteolytic and inhibitory sites of the plasmin-antiplasmin and thrombin-antithrombin systems, the main chains of the extracellular matrix protection proteins, the excessive degradation of innate immune system key convertases and membrane attack complex components, as well as several other cancer suppressor proteins.ConclusionsDegradomics-peptidomics profiling of blood plasma is highly sensitive to changes not evidenced by conventional bottom-up proteomics and potentially provides unique signatures of possible diagnostic utility.
| S-EPMC2956627 | biostudies-literature
Project description:The objective was to evaluate the effect of nutrient restriction and intramammary lipopolysaccharide (LPS) challenge on mammary gland (MG) gene expression in early lactation cows. At 24 ± 3 d in milk, multiparous cows were either allowed to continue ad libitum intake of a lactation diet (CON, n = 6), or the ration was diluted with barley straw (48% DM) for 4 d (RES, n = 6). On d 3, one healthy rear mammary quarter was infused with 50 µg of LPS. Mammary biopsies were performed 24 h after LPS challenge. RNA and proteins analyzed using bovine 44K microarrays (Agilent Technologies) and micro-LC-MS/MS, respectively. Transcriptomic data were analyzed using GeneSpring (moderated-t-test with Westfall-Young correction, P < 0.05). Proteins were analyzed with Progenesis LC-MS software v4.1 (Nonlinear Dynamics). Production and energy balance did not differ prior to diet change. Negative energy balance was aggravated in RES (41 vs 97 ± 15 % of requirements, mean ± SD; P < 0.001). A total of 87 differentially expressed genes (DEG) were highlighted through the comparison of RES vs CON group. Among the 33 DEG identified in the transcriptomic analyses, 11 and 22 were down- and upregulated by restriction, respectively. Among the upregulated DEG, there were PDK4 and CPT1A which are involved in the regulation of fatty acid, ketone, and glucose metabolism. CPT1A is the key enzyme in the carnitine dependent fatty acid transport, promoting fatty acid oxidation. Genes involved in immune response such as PGLYRP3 and TRIB2 were upregulated, suggesting a higher inflammatory response in RES than CON. Proteomic analysis identified 54 proteins with 14 up- and 40 downregulated in RES cows. Upregulated proteins were mostly involved in gene expression mechanisms such as translation, RNA splicing and cellular protein modification. The downregulated proteins (e.g., EIF3H, RS27A, RS15) take part in protein metabolism. This is coherent with transcriptomic results, namely the downregulation of RPL 37A, a component of ribosomal complex, which catalyzes protein synthesis and may partially explain the lower milk protein yield in RES (834 vs 1163 g/d; P = 0.02). Proteins involved in antigen processing and presentation were downregulated in RES compared to CON, suggesting an impaired ability to counteract inflammation in RES MG. Preliminary transcriptomics and proteomics analyses show that undernutrition may influence the MG response to inflammation at each level of gene expression.
2019-03-27 | GSE114975 | GEO
Project description:Breast cancer occurring during pregnancy (PrBC) and postpartum (PPBC) is usually diagnosed at more advanced stages compared with other breast cancer, worsening its prognosis. PPBC is particularly aggressive, with increased metastatic risk and mortality. Thus, effective screening methods to detect early PrBC and PPBC are needed. We report for the first time that cell-free tumor DNA (ctDNA) is present in breast milk (BM) collected from patients with breast cancer. Analysis of ctDNA from BM detects tumor variants in 87% of the cases by droplet digital PCR, while variants remain undetected in 92% of matched plasma samples. Retrospective next-generation sequencing analysis in BM ctDNA recapitulates tumor variants, with an overall clinical sensitivity of 71.4% and specificity of 100%. In two cases, ctDNA was detectable in BM collected 18 and 6 months prior to standard diagnosis. Our results open up the potential use of BM as a new source for liquid biopsy for PPBC detection.SignificanceFor the first time, we show that BM obtained from patients with breast cancer carries ctDNA, surpassing plasma-based liquid biopsy for detection and molecular profiling of early-stage breast cancer, even prior to diagnosis by image. See related commentary by Cunningham and Turner, p. 2125. This article is featured in Selected Articles from This Issue, p. 2109.
| S-EPMC10551665 | biostudies-literature
Project description:Copy number alteration profiling of human early-stage (stage I and II) breast cancers. We aimed to describe the commonly occurred chromosome alterations in early-stage breast cancer (stage I and II) and to explore the implications of the recurrently altered regions (RAR) on the patient prognosis. For this purpose, we analyzed the DNA copy number alterations (CNAs) across the whole genome using oligoarray-comparative genomic hybridization (CGH) in the discovery set of EBC patients.
2012-05-09 | GSE37839 | GEO
Project description:Large scale study on human fibroblast, IMR90, by top-down proteomics on a benchtop Orbitrap QExactive HF instrument. RAW files were collected in three main modes: (i) data-dependent top-2 with high resolution for both MS1 and MS2, or hi/hi; (ii) in hi/hi using the in-house written instrument control software AUTOPILOT; (iii) in med/hi mode, where MS1 scans are acquired with short transients.
2016-07-15 | MSV000079913 | MassIVE
Project description:Copy number alteration profiling of human early-stage (stage I and II) breast cancers. We aimed to describe the commonly occurred chromosome alterations in early-stage breast cancer (stage I and II) and to explore the implications of the recurrently altered regions (RAR) on the patient prognosis. For this purpose, we analyzed the DNA copy number alterations (CNAs) across the whole genome using oligoarray-comparative genomic hybridization (CGH) in the discovery set of EBC patients. 48 cases of early-stage breast cancer were used in this study.
2012-05-08 | E-GEOD-37839 | biostudies-arrayexpress
Project description:MiRNA profiling from whole blood (EDTA) was used to identify a miRNA profile applicable for early stage breast cancer detection In the study presented here, a consecutively collected, well-defined cohort of 48 patients with early stage breast cancer (invasive ductal carcinoma) at diagnosis was compared with a cohort of 57 healthy individuals for known homo sapiens miRNAs (mirbase 15).
| S-ECPF-GEOD-31309 | biostudies-other
Project description:To identity the targets of miRNAs, we bundled 12 samples from different developing satages into four mixture samples. These samples were used to cosntruct degradome libraries and preform degradome sequencing on Illumina Hi-seq 2000 analyzer. More than 44.98 millions clean reads were obtained and 33.52 million reads were mapped to the soybean cDNA. The mapped reads were used to identity miRNA targets by CleaveLand4 pipeline. 4 degradome mixed samples, no replicates, but every degradome data consists of two parts data. Please note that every degradome sample has two processed and two raw data files. To have enough data, additional sequencing was performed from each sample library. And each sample raw data was processed separately (tissue_name*degradome.txt) and also combined (all_degradome*.txt).
2017-05-01 | E-GEOD-72903 | biostudies-arrayexpress
Project description:BackgroundMost women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.MethodsWe randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group). The primary outcome was overall survival. Secondary outcomes were disease-free survival, isolated locoregional disease-free survival, and distant disease-free survival.ResultsBetween March 2000 and February 2007, a total of 1832 women were assigned to the nodal-irradiation group or the control group (916 women in each group). The median follow-up was 9.5 years. At the 10-year follow-up, there was no significant between-group difference in survival, with a rate of 82.8% in the nodal-irradiation group and 81.8% in the control group (hazard ratio, 0.91; 95% confidence interval [CI], 0.72 to 1.13; P=0.38). The rates of disease-free survival were 82.0% in the nodal-irradiation group and 77.0% in the control group (hazard ratio, 0.76; 95% CI, 0.61 to 0.94; P=0.01). Patients in the nodal-irradiation group had higher rates of grade 2 or greater acute pneumonitis (1.2% vs. 0.2%, P=0.01) and lymphedema (8.4% vs. 4.5%, P=0.001).ConclusionsAmong women with node-positive or high-risk node-negative breast cancer, the addition of regional nodal irradiation to whole-breast irradiation did not improve overall survival but reduced the rate of breast-cancer recurrence. (Funded by the Canadian Cancer Society Research Institute and others; MA.20 ClinicalTrials.gov number, NCT00005957.).
| S-EPMC4556358 | biostudies-literature
Project description:To identity the targets of miRNAs, we bundled 12 samples from different developing satages into four mixture samples. These samples were used to cosntruct degradome libraries and preform degradome sequencing on Illumina Hi-seq 2000 analyzer. More than 44.98 millions clean reads were obtained and 33.52 million reads were mapped to the soybean cDNA. The mapped reads were used to identity miRNA targets by CleaveLand4 pipeline.
2017-05-01 | GSE72903 | GEO