Gene expression profiling of human breast cancer during pregnancy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Azim HA Jr
PROVIDER: S-ECPF-GEOD-53031 | biostudies-other | 2014 Aug
REPOSITORIES: biostudies-other
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Project description:Using a dataset of 54 pregnant and 113 age/stage-matched non-pregnant breast cancer patients with complete clinical and survival data; we evaluated the pattern of hot spot somatic mutations and performed transcriptomic profiling using Sequenom® and Affymetrix®, respectively. Breast cancer molecular subtypes were defined using PAM50 and 3-Gene classifiers. We performed Gene set enrichment analysis (GSEA) to evaluate pathways associated with diagnosis during pregnancy. We investigated the differential expression of cancer-related genes and published gene sets according to pregnancy. We finally investigated genes associated with disease-free survival.
2014-09-09 | GSE53031 | GEO
Project description:Using a dataset of 54 pregnant and 113 age/stage-matched non-pregnant breast cancer patients with complete clinical and survival data; we evaluated the pattern of hot spot somatic mutations and performed transcriptomic profiling using Sequenom® and Affymetrix®, respectively. Breast cancer molecular subtypes were defined using PAM50 and 3-Gene classifiers. We performed Gene set enrichment analysis (GSEA) to evaluate pathways associated with diagnosis during pregnancy. We investigated the differential expression of cancer-related genes and published gene sets according to pregnancy. We finally investigated genes associated with disease-free survival. We identified 65 patients who were diagnosed with breast cancer during pregnancy. Moreover, for each case, two breast cancer patients who were not diagnosed during pregnancy or lactation, but who were matched according to age (±2 years), tumors size, nodal status, year of surgery (±2 years) and whether neoadjuvant chemotherapy was received were selected. Messenger RNA from tumor tissue has been extracted and hybridized on Affymetrix microarrays. However, due to experimental issues, 54 pregnant and 113 non-pregnant patients were remaining and used in our study.
2014-09-09 | E-GEOD-53031 | biostudies-arrayexpress
Project description:IntroductionThe importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma.MethodsWe combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed.ResultsTumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response.ConclusionsOur results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.
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Project description:The neurophysiological changes that occur during pregnancy in the female mammal have led to the coining of the phrases "expectant brain" and "maternal brain". Although much is known of the hormonal changes during pregnancy, alterations in neurotransmitter gene expression have not been well-studied. We examined gene expression in the ventromedial nucleus of the hypothalamus (VMH) during pregnancy based on the fact that this nucleus not only modulates the physiological changes that occur during pregnancy but is also involved in the development of maternal behavior. This study was designed to identify genes that are differentially expressed between mid- and late-pregnancy in order to determine which genes may be associated with the onset and display of maternal behavior and the development of the maternal brain. A commercially available PCR array containing 84 neurotransmitter receptor and regulator genes (RT2 Profiler PCR array) was used. Brains were harvested from rats on days 12 and 21 of gestation, frozen, and micropunched to obtain the VMH. Total RNA was extracted, cDNA prepared, and SYBR Green qPCR was performed. In the VMH, expression of five genes were reduced on day 21 of gestation compared to day 12 (Chrna6, Drd5, Gabrr2, Prokr2, and Ppyr1) whereas Chat, Chrm5, Drd4, Gabra5, Gabrg2, LOC289606, Nmu5r2, and Npy5r expression was elevated. Five genes were chosen to be validated in an additional experiment based on their known involvement in maternal behavior onset. This experiment confirmed that gene expression for both the CCK-A receptor and the GABAAR γ2 receptor increases at the end of pregnancy. In general, these results identify genes possibly involved in the establishment of the maternal brain in rats and indicate possible new genes to be investigated.
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Project description:UnlabelledPreeclampsia is a major obstetrical complication affecting maternal and fetal health. While it is clear that there is a substantial placental contribution to preeclampsia pathogenesis, the maternal contribution is less well characterized. We therefore performed a genome-wide transcriptome analysis to explore disease-associated changes in maternal gene expression patterns in peripheral blood mononuclear cells (PBMCs).MethodsPreeclampsia was defined as gestational hypertension, proteinuria and hyperurecimia. Total RNA was isolated from PBMCs obtained from women with uncomplicated pregnancies (n = 5) and women with preeclamptic pregnancies (n = 5). Gene expression analysis was carried out using Agilent oligonucleotide microarrays. Biological pathway analysis was undertaken using Ingenuity Pathway Analysis software. Quantitative real-time PCR (QRTPCR) was performed to validate the gene expression changes of selected genes in normotensive and preeclamptic patients (n = 12 each).ResultsWe identified a total of 368 genes that were differentially expressed in women with preeclampsia compared to normal controls with false discovery rate (FDR) controlled at 10%. In follow up experiments we further analyzed the expression levels of a number of genes that were identified as altered by the microarray data including survivin (BIRC5), caveolin (CAV1), GATA binding protein-1 (GATA1), signal tranducer and activator of transcription 1 (STAT1), E2F transcription factor-1 (E2F1), fibronectin-1 (FN1), interleukin-4 (IL-4), matrix metalloprotease-9 (MMP-9) and WAP four disulfide domain protein (WFDC-1) by QRTPCR. Additionally we performed immuno blot analysis and zymography to verify some of these candidate genes at the protein level. Computational analysis of gene function identified an anti-proliferative and altered immune function cellular phenotype in severe preeclamptic samples.ConclusionsWe have characterized the genome-wide mRNA expression changes associated with preeclampsia-specific genes in circulating maternal blood cells at the time of delivery. In addition to providing information relating to the biological basis of the preeclampsia phenotype, our data provide a number of potential biomarkers for use in the further characterization of this disease.
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