Breast Cancer - Very young women
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001001908 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:miRNA expression from breast tumor tissue obtained from two groups of breast cancer (BC) patients: one group formed by women younger than 36 years and the other group by women older than 65 years. We selected breast tumor tissue samples from 21 women under 36 years old and 12 women above 65 years old, without BRCA mutation and without metastases. We selected a pool of samples in which all the subtypes were representated, in young patients as well as in older patients, to avoid expression biass. We add three samples from breast tissue of cancer-free women to minimize the age-related expression biass. Our aim was to compare miRNA expression between young women and older women, considering normal tissue as a reference.
2014-09-12 | E-GEOD-48088 | biostudies-arrayexpress
Project description:Breast cancer in young patients is known to exhibit more aggressive biological behavior and is associated with a less favorable prognosis than the same disease in older patients, owing in part to an increased incidence of brain metastases, the mechanistic explanations behind which remain poorly understood. We recently reported that young mice, compared to older mice, showed about a three-fold increase in the development of brain metastases in mouse models of triple-negative and luminal B breast cancer. Here we have performed a quantitative mass spectrometry-based proteomic analysis to identify proteins contributing to age-related disparities in the development of breast cancer brain metastases. Using a mouse model of brain-tropic (MDA-MB-231BR) triple-negative breast cancer, we harvested subpopulations of tumor metastases, the tumor-adjacent metastatic microenvironment, and uninvolved brain tissues via laser microdissection followed by quantitative proteomic analysis using high resolution mass spectrometry to characterize differentially abundant proteins contributing to age-dependent rates of brain metastasis.
2024-01-11 | PXD042346 | Pride
Project description:Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data show that from adolescence through middle age, cancer incidence increases with age. This effect is commonly attributed to a lifetime accumulation of cellular, particularly DNA, damage. However, during middle-age, the incidence begins to decelerate and, for many tumor sites, it actually decreases at sufficiently advanced ages. We investigated if the observed deceleration and potential decrease in incidence could be attributed to a decreased capacity of older hosts to support tumor progression, and whether HZE (high atomic number (Z), high energy (E)) radiation differentially modulates tumor progression in young versus middle-age hosts, issues relevant to estimating carcinogenesis risk for astronauts. Lewis lung carcinoma (LLC) cells were injected into syngeneic mice (143 and 551 days old), which were then subject to whole-body 56Fe irradiation (1GeV/amu). Three findings emerged: 1) among unirradiated animals, substantial inhibition of tumor progression and significantly decreased tumor growth rates were seen for middle-aged mice compared to young mice; 2) whole-body 56Fe irradiation (1GeV/amu) inhibited tumor progression in both young and in middle-aged mice (with greater suppression seen in case of young animals), with little effect on tumor growth rates; and 3) 56Fe irradiation (1GeV/amu) suppressed tumor progression in young mice, to a degree not significantly different than transiting from young to middle-aged. Thus, 56Fe irradiation (1GeV/amu) acted similar to aging with respect to tumor progression. We further investigated the molecular underpinnings driving the radiation modulation of tumor dynamics in young and middle-aged mice. Through global gene expression analysis, the key players, FASN, AKT1, and the CXCL12/CXCR4 complex, were determined to be contributory. In sum, these findings demonstrate a reduced capacity of middle-aged hosts to support the progression phase of carcinogenesis and identify molecular factors contributory to HZE radiation modulation of tumor progression as a function of age.
2013-06-13 | GSE45606 | GEO
Project description:To investigate the biological basis between aging and sporadic breast cancer incidence and prognosis, RNA samples from matched ER+ invasive breast cancers diagnosed in either young (â?¤45) or old (â?¥70) women were analyzed by expression microarrays Experiment Overall Design: ER+ breast cancers collected from either young or old women, well matched for other clinical parameters were analyzed using expression microarrays. Age associated tumor subtypes and enrichment of pre-defined gene signatures were identified. Age associated differential expression and an age signature (gene-based classifier) was assessed
2008-06-16 | E-GEOD-8193 | biostudies-arrayexpress
Project description:Breast cancer in very young women (< 35 years BCVY) presents more aggressive and complex biological features than in their older counterparts. In this study we aimed to identify the key pathways that may cause cancer in this younger age group. EPIC and 450k Illumina methylation arrays were used to identify differences in DNA methylation in 74 breast cancer tumours, including 37 from very young women. Additionally, we analysed copy number variation (CNV) and DNAm age using methylation intensities from Illumina Infinium MethylationEPIC BeadChip. Although we are able to identify aberrant CNV patterns in breast cancer samples, they were not highly specific to BCVY. However, we identified 2 219 CpG sites that were differently methylated in BCVY vs. older women (false discovery rate < 0.05 beta-value difference ± 0.1), with the general hypomethylation profile affecting genes involved in neuronal-system pathways, cell communication, and extracellular matrix organisation, as confirmed by our experimental data. Additionally, a specific hypermethylation profile comprising 502 CpG sites located mainly in open-sea regions distinguished BCVY from older patients. Pathway enrichment analysis showed that regions implicated in the hypermethylation profile were involved in regulating genes related to Notch signalling pathways, the immune system, DNA repair, and vesicular trafficking. Moreover, BCVY presented age acceleration comparing with older women. The expression of genes regulated by differentially-methylated CpG sites was validated using both Cancer Genome Atlas genomic data and by qRT-PCR, the latter in an independent sample (n = 40). This validation highlighted that 186 genes were consistently deregulated, including consistent hypomethylation and higher expression of HOXD9, PCDH10, and HDAC5 genes when considering BCVY vs. BC. Thus, we propose HDAC5 hypomethylation as a possible early detection biomarker in BCVY, and moreover, HDAC5 inhibitors, such as LMK-235, may be useful in treating breast cancer tumours in young women
2018-10-16 | GSE100850 | GEO
Project description:Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data show that from adolescence through middle age, cancer incidence increases with age. This effect is commonly attributed to a lifetime accumulation of cellular, particularly DNA, damage. However, during middle-age, the incidence begins to decelerate and, for many tumor sites, it actually decreases at sufficiently advanced ages. We investigated if the observed deceleration and potential decrease in incidence could be attributed to a decreased capacity of older hosts to support tumor progression, and whether HZE (high atomic number (Z), high energy (E)) radiation differentially modulates tumor progression in young versus middle-age hosts, issues relevant to estimating carcinogenesis risk for astronauts. Lewis lung carcinoma (LLC) cells were injected into syngeneic mice (143 and 551 days old), which were then subject to whole-body 56Fe irradiation (1GeV/amu). Three findings emerged: 1) among unirradiated animals, substantial inhibition of tumor progression and significantly decreased tumor growth rates were seen for middle-aged mice compared to young mice; 2) whole-body 56Fe irradiation (1GeV/amu) inhibited tumor progression in both young and in middle-aged mice (with greater suppression seen in case of young animals), with little effect on tumor growth rates; and 3) 56Fe irradiation (1GeV/amu) suppressed tumor progression in young mice, to a degree not significantly different than transiting from young to middle-aged. Thus, 56Fe irradiation (1GeV/amu) acted similar to aging with respect to tumor progression. We further investigated the molecular underpinnings driving the radiation modulation of tumor dynamics in young and middle-aged mice. Through global gene expression analysis, the key players, FASN, AKT1, and the CXCL12/CXCR4 complex, were determined to be contributory. In sum, these findings demonstrate a reduced capacity of middle-aged hosts to support the progression phase of carcinogenesis and identify molecular factors contributory to HZE radiation modulation of tumor progression as a function of age. For genome-wide expression profiling of tumor tissue, Mouse WG-6 BeadArray chips (Illumina, San Diego, CA) were used. Total RNA was amplified with the Ambion Illumina TotalPrep Amplification Kit (Ambion, Austin, TX) and labeled from all replicate biological samples for each condition. The number of tumor sample replicates used from each condition is as follows: 10 samples from young unirradiated mice, 8 samples from young irradiated mice, 7 samples from middle-aged unirradiated mice, 5 samples from middle-aged irradiated mice. Total RNA was isolated and purified using Trizol (Invitrogen) or RNeasy (Qiagen), quantified and qualified using Agilent Bioanalyzer (Agilent) and samples were deemed suitable for amplification and hybridization if they had O.D. 260/280 = 1.7 - 2.1, 28s/18s = 2:1, RIN (RNA integrity number) >7. Total RNA of 500ng per sample was amplified using Ambion TotalPrep (Ambion), and 1.5µg of the product was loaded onto the chips. Following hybridization at 55C, the chips were washed and then scanned using the Illumina iScan (Illumina), and the data were analyzed using GenomeStudio (Illumina). Data were first analyzed for gene expression and then culled for present genes (genes that meet the criteria of detection p-value < 0.05). Expression above background was included in an expressed genes working data set for further analyses. Rank variant normalization was applied to the data before extensive analysis. Differential gene expression analysis was used to compare to the reference group, young unirradiated mice, and genes were then evaluated and validated.
2013-06-13 | E-GEOD-45606 | biostudies-arrayexpress
Project description:Background: Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women’s breast cancer may be more aggressive. Though several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues. Methods: To identify age-related changes in normal breast tissue, 96 tissue specimens from reduction mammoplasty patients aged 14 to 70 were assayed by gene expression microarray. Results: Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included ‘aging of cells’, ‘shape change’, and ‘chemotaxis’, and enriched pathways included Wnt/beta-catenin signaling, Ephrin Receptor Signaling, and JAK/Stat Signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. Conclusion: The hazard rates of young-like tumors mirrored that of high grade tumors in the Surveillance, Epidemiology and End Results Program, providing a biological link between normal aging and age-related tumor aggressiveness. Impact: These data show that studies of normal tissue gene expression can yield important insights about the pathways and biological pressures that are relevant during tumor etiology and progression. reference x sample
2013-08-31 | E-GEOD-43973 | biostudies-arrayexpress
Project description:Background: Age is the strongest breast cancer risk factor, with overall breast cancer risk increasing steadily beginning at approximately 30 years of age. However, while breast cancer risk is lower among younger women, young women’s breast cancer may be more aggressive. Though several genomic and epidemiologic studies have shown higher prevalence of aggressive, estrogen-receptor negative breast cancer in younger women, the age-related gene expression that predisposes to these tumors is poorly understood. Characterizing age-related patterns of gene expression in normal breast tissues may provide insights on etiology of distinct breast cancer subtypes that arise from these tissues. Methods: To identify age-related changes in normal breast tissue, 96 tissue specimens from reduction mammoplasty patients aged 14 to 70 were assayed by gene expression microarray. Results: Significant associations between gene expression levels and age were identified for 802 probes (481 increased, 321 decreased with increasing age). Enriched functions included ‘aging of cells’, ‘shape change’, and ‘chemotaxis’, and enriched pathways included Wnt/beta-catenin signaling, Ephrin Receptor Signaling, and JAK/Stat Signaling. Applying the age-associated genes to publicly available tumor datasets, the age-associated pathways defined two groups of tumors with distinct survival. Conclusion: The hazard rates of young-like tumors mirrored that of high grade tumors in the Surveillance, Epidemiology and End Results Program, providing a biological link between normal aging and age-related tumor aggressiveness. Impact: These data show that studies of normal tissue gene expression can yield important insights about the pathways and biological pressures that are relevant during tumor etiology and progression.
2013-08-31 | GSE43973 | GEO
Project description:The incidence of prostate cancer is directly linked to age, but we still lack an adequate understanding of the prostatic aging-associated changes that facilitate carcinogenesis. In this study, we investigated possible associated factors in the aged prostate microenvironment, using an orthotopic mouse model of prostate cancer. We found that aged mice showed accelerated growth of TRAMP-C2 cells, compared with young mice. Metastatic lesions following intravenous injection were also more numerous in aged mice. TRAMP-C2 tumors from young and aged mice showed no significant differences concerning their proliferation index, apoptosis or angiogenesis. However, analysis of tumor-infiltrating immune cells by immunohistochemistry and RNA-seq gene expression revealed that aged mice present higher numbers of macrophages in normal prostatic tissue and that these are quickly polarized towards an M2 phenotype upon TRAMP-C2 cells engraftment.
2019-04-23 | GSE110643 | GEO
Project description:Breast cancer arising in young women has a poorer prognosis, is less likely to be hormone sensitive, and represents a particularly challenging clinical entity. The biology driving the aggressive nature of breast cancer arising in young women has yet to be defined. Among 784 patients with early stage breast cancer, using prospectively-defined, age-specific cohorts (young <= 45 years; older >= 65 years), 411 eligible patients (n = 200 < 45 years; n = 211 >= 65 years) with clinically-annotated Affymetrix microarray data were identified. Gene set enrichment analyses, signatures of oncogenic pathway deregulation and predictors of chemotherapy sensitivity were evaluated within the two age-defined cohorts. In comparing deregulation of oncogenic pathways between age groups, a statistically higher probability of PI3K (p = 0.006) and Myc (p = 0.03) pathway deregulation was observed in the tumors of younger women. When evaluating unique patterns of pathway deregulation, a low probability of Src and E2F deregulation in tumors of younger women, concurrent with activation of PI3K, Myc, and beta-catenin, conferred a worse prognosis (HR = 4.15; p = 0.008). In contrast, a higher probability of Src and E2F pathway activation in tumors of older women, concurrent low probability of PI3K, Myc and beta-catenin deregulation, was associated with a poorer outcome (HR = 2.7; p = 0.006). Similar pathway differences were identified using gene set enrichment analysis. Importantly, in multivariate analyses including clinico-pathologic variables, genomic clusters of pathway deregulation were identified to be independent predictors of disease-free survival. Finally, a significant relationship (p = 0.02) between anthracycline sensitivity and genomic clusters was observed among women aged >= 65 years. Submitters do not have approval to publish the .CEL files Experiment Overall Design: n=78
2008-06-15 | E-GEOD-7849 | biostudies-arrayexpress