MiRNA profiling array results in serum RNA (healthy volunteers and breast tumor patients)
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jian Guo
PROVIDER: E-MTAB-6652 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
2022-05-01 | PXD027668 | Pride
Project description:Metastasis is responsible for the majority of deaths in a variety of cancer types, including breast cancer. Although several factors or biomarkers have been identified to predict the outcome of patients with breast cancer, few studies have been conducted to identify metastasis-associated biomarkers. Quantitative iTRAQ proteomics analysis was used to detect differentially expressed proteins between lymph node metastases and their paired primary tumor tissues from 23 patients with metastatic breast cancer. Immunohistochemistry was performed to validate the expression of two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins in 190 paraffin-embedded tissue samples. These four proteins were further analyzed for their correlation with clinicopathological features in 190 breast cancer patients. We identified 637 differentially regulated proteins (397 upregulated and 240 downregulated) in lymph node metastases compared with their paired primary tumor tissues. Furthermore, bioinformatics analysis using GEO profiling confirmed the difference in the expression of EpCAM between metastases and primary tumors tissues. Two upregulated (EpCAM, FADD) and two downregulated (NDRG1, αB-crystallin) proteins were associated with the progression of breast cancer. Obviously, EpCAM plays a role in the metastasis of breast cancer cells to the lymph node. We further identified αB-crystallin as an independent biomarker to predict lymph node metastasis and the outcome of breast cancer patients.
2019-08-29 | PXD013931 | Pride
Project description:Background: Gene expression profiling of breast carcinomas has increased our understanding of the heterogeneous biology of this disease and promises to impact clinical care. The aim of this study was to evaluate the prognostic value of gene expression-based classification along with established prognostic markers and mutation status of the TP53 gene, in a group of breast cancer patients with long-term (12-16 years) follow-up. Methods: The clinical and histopathological parameters of 200 breast cancer patients were studied for their effects on clinical outcome using univariate/multivariate Cox regression. The prognostic impact of mutations in the TP53 gene, identified using TTGE and sequencing, was also evaluated. Eighty of the samples were analyzed for gene expression using 42K cDNA microarrays and the patients were assigned to five previously defined molecular expression groups. The strength of the gene expression based classification versus standard markers was evaluated by adding this variable to the Cox regression model used to analyze all samples. Results: Both univariate and multivariate analysis showed that TP53 mutation status, tumor size and lymph node status were the strongest predictors of breast cancer survival for the whole group of patients. Analyses of the patients with gene expression data showed that TP53 mutation status, gene expression based classification, tumor size and lymph node status were significant predictors of survival. The TP53 mutation status showed strong association with the ?basal-like? and ?ERBB2+? gene expression subgroups, and tumors with mutation had a characteristic gene expression pattern. Conclusions: TP53 mutation status and gene-expression based groups are important survival markers of breast cancer, and these molecular markers may provide prognostic information that complements clinical variables. The study adds experience and knowledge to an ongoing characterization and classification of the disease. Experiment set consisting of 80 primary breast carcinomas collected at Ulleval University Hospital (ULL-samples), Oslo, Norway from 1990-94, and one normal sample from breast reduction surgery.
2012-09-18 | E-GEOD-40954 | biostudies-arrayexpress
Project description:Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder leading to debilitating symptoms and the therapeutic alternatives are limited. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification on patients based on their protein background. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique. We aimed to explore proteins that may be related with the putative etiology of POTS compared with healthy controls using a highly powerful targeted proteomic mass spectrometry technique.
2022-11-24 | PXD031458 | Pride
Project description:Background. Although gene expression arrays have been used to generate molecular predictors of relapse and drug sensitivity in breast cancer, no large study describes genes and exons differentially expressed between breast cancer and benign lesions.<br><br> Methods. One hundred and sixty-five tumour samples were obtained by fine needle aspiration (FNA). cDNA were hybridized on Splice ArrayTM. A nearest centroid prediction rule was developed to classify lesions as malignant or benign on a training set, and its performance evaluated on an independent validation set. A two-way ANOVA model was used to identify probesets that present a differential expression between cancer and benign lesions while adjusting for scan dates. P-values were adjusted for False Discovery Rate.<br><br>Findings. Overall 120 breast cancers and 45 benign lesions were included in the study. A 1228-probeset molecular classifier for breast cancer diagnosis was generated from the training set (n=94). This signature accurately classified all samples (100% accuracy, 95% exact CI: 96-100%). In the validation set (n=71), the molecular predictor accurately classified 68 out of 71 tumours (96%, 95% CI: 88-99%). When the 165 samples were taken into account, 37 858 exon-probesets (5.4%) and 3733 genes (20%) were found to be differentially expressed between malignant and benign conditions (adjusted p-value<0.05). Pathway analyses showed that genes involved in spliceosome assembly were significantly enriched in malignant condition (permutation p=0.002). In the same population of 165 samples, 956 exon-probesets presented both a higher intensity and higher splice index in breast cancer, although located on unchanged genes.<br><br> Interpretation. The present study provides a thorough description of differentially expressed exons between breast cancer and benign lesions, and emphasizes the contribution of spliceosome and alternative transcripts to the molecular portrait of breast malignancy. This allowed the development of a molecular classifier for breast cancer diagnosis using FNA.
2009-12-30 | E-TABM-609 | biostudies-arrayexpress
Project description:The human breast cancer (BR) data set (endpoints D and E) was contributed by the University of Texas M. D. Anderson Cancer Center (MDACC, Houston, TX, USA). Gene expression data from 230 stage I-III breast cancers were generated from fine needle aspiration specimens of newly diagnosed breast cancers before any therapy. The biopsy specimens were collected sequentially during a prospective pharmacogenomic marker discovery study between 2000 and 2008. These specimens represent 70-90% pure neoplastic cells with minimal stromal contamination. Patients received 6 months of preoperative (neoadjuvant) chemotherapy including paclitaxel, 5-fluorouracil, cyclophosphamide and doxorubicin followed by surgical resection of the cancer. Response to preoperative chemotherapy was categorized as a pathological complete response (pCR = no residual invasive cancer in the breast or lymph nodes) or residual invasive cancer (RD), and used as endpoint D for prediction. Endpoint E is the clinical estrogen-receptor status as established by immunohistochemistry. RNA extraction and gene expression profiling were performed in multiple batches over time using Affymetrix U133A microarrays. Genomic analysis of a subset of this sequentially accrued patient population were reported previously. For each endpoint, the first 130 cases were used as a training set and the next 100 cases were used as an independent validation set. Gene expression data from 230 stage I-III breast cancers
2010-02-04 | E-GEOD-20194 | biostudies-arrayexpress
Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.
2004-09-23 | E-GEOD-1743 | biostudies-arrayexpress
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Project description:Articular cartilage is deprived of blood vessels and nerves, and the only cells residing in this tissue are chondrocytes. The molecular properties of the articular cartilage and the architecture of the extracellular matrix demonstrate a complex structure that differentiates on the depth of tissue. Osteoarthritis (OA) is a degenerative joint disease, the most common form of arthritis, affecting the whole joint. It is associated with ageing and affects the joints that have been continually stressed throughout life including the knees, hips, fingers, and lower spine region. OA is a multifactorial condition of joint characterised by articular cartilage loss, subchondral bone sclerosis, and inflammation leading to progressive joint degradation, structural alterations, loss of mobility and pain. Articular cartilage biology is well studied with a focus on musculoskeletal diseases and cartilage development. However, there are relatively few studies focusing on zonal changes in the cartilage during osteoarthritis.
2022-05-19 | PXD029116 | Pride
Project description:Intra-tumor heterogeneity (ITH) results from coexistence of genetically distinct cancer cell (sub)populations, their phenotypic plasticity, and the presence of heterotypic components of the tumor microenvironment (TME). Here we addressed potential association between phenotypic ITH revealed by mass spectrometry imaging (MSI) and the prognosis of breast cancer. Tissue specimens resected from 59 patients treated radically due to the locally advanced HER2-positive invasive ductal carcinoma were included in the study. After on-tissue trypsin digestion of cellu-lar proteins, peptide maps of all cancer regions (about 380,000 spectra in total) were segmented by an unsupervised approach to reveal their intrinsic heterogeneity. A high degree of similarity between spectra was observed, which indicated relative homogeneity of cancer regions. How-ever, when the number and diversity of the detected clusters of spectra were analyzed, differ-ences between patient groups were observed. It is noteworthy that a higher degree of heteroge-neity was found in tumors from patients who remained disease-free during a 5-year follow-up (n=38) compared to tumors from patients with progressive disease (distant metastases detected during follow-up, n=21). Interestingly, such differences were not observed between patients with different status of regional lymph nodes, cancer grade, or expression of estrogen receptor at the time of the primary treatment. Subsequently, spectral components with different abundance in cancer regions were detected in patients with different outcomes, and their hypothetical identity was established by assignment to measured masses of tryptic peptides identified in correspond-ing tissue lysates. Such differentiating components were associated with proteins involved in immune regulation and hemostasis. We postulate that a higher heterogeneity of tumors with a better prognosis could reflect the presence of heterotypic components including the microvas-culature and infiltrating immune cells, that facilitated response to treatment.
2022-02-17 | PXD027878 | Pride