Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA296844 | ENA |
REPOSITORIES: ENA
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Project description:Breast carcinoma (BC) is the leading cause of death in women worldwide, making up 23% of all cancers in women, with 1.38 million new cases worldwide annually and responsible for 460,000 deaths. Despite the significant advances in the identification of molecular markers and different modalities of treatment in primary BC, the ability to predict the metastatic behavior in breast cancer is still limited. The purpose of this study was to help identify novel molecular markers associated with clinical outcome in a cohort of Brazilian BC patients. We generated global gene expression profiles from 24 patients with invasive ductal BC followed for ⥠5-years, including 15 samples from patients classified as presenting good prognosis based on traditional markers and clinical criteria and 9 patients that developed metastasis. We identified a set of 58 differentially expressed genes (p â¤0.01) between groups of patients with good and poor prognosis. Up-regulation of B3GNT7, PPM1D, TNKS2, PHB and GTSE1 in patients with poor prognosis was confirmed by quantitative RT-PCR in an independent sample set from patients with BC (47 with good prognosis and 8 that presented metastasis). Expression of BAD protein was investigated by immunohistochemistry in 1276 BC samples and confirmed the reduced expression levels in metastatic cases observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinoma samples according to clinical course and progression of the disease. Global expression profiles from 38 ductal breast tumor patient samples were used to search for molecular signatures correlated with current prognostic markers. A subset of 24 cases comprising 15 patients that remained free of disease after surgery and 9 patients that developed metastasis was used to identify candidate biomarkers associated with metastatic progression. Candidates were subsequently validated in additional independent samples by RT-qPCR or immunohistochemistry.
2016-06-30 | E-GEOD-73383 | biostudies-arrayexpress
Project description:Dysregulation of the PI3K/AKT pathway is a common occurrence in ovarian carcinomas. Loss of the tumour suppressor PTEN in high-grade serous ovarian carcinoma (HGSOC) is associated with a patient subgroup with poor prognosis. The cellular mechanisms of how PTEN loss contributes to HGSOC are largely unknown. We utilise long-term time-lapse imaging of HGSOC spheroids coupled to a machine learning approach to classify the phenotype of PTEN loss. PTEN deficiency does not affect proliferation but rather induces PI(3,4,5)P3-rich and -dependent membrane protrusions into the extracellular matrix (ECM), resulting in a collective invasion phenotype. We identify the small GTPase ARF6 as a crucial vulnerability upon PTEN loss. Through a functional proteomic CRISPR screen of ARF6 interactors, we identify the ARF GTPase-activating protein (GAP) AGAP1 and the ECM receptor β1-integrin as key ARF6 interactors regulating the PTEN loss-associated invasion phenotype. ARF6 functions to promote invasion by controlling the recycling of internalised, active β1-integrin complexes to maintain invasive activity into the ECM. The expression of the ARF6-centred complex in HGSOC patients is inversely associated with outcome, allowing identification of patient groups with improved versus poor outcome. ARF6 may represent a new therapeutic vulnerability in PTEN-depleted HGSOC tumours.
2023-07-11 | PXD038305 | Pride
Project description:We performed Chip-Seq analyses of several DNA binding transcription factors predicted to function as "master transcriptional regulators" (MTRs) of breast cancer prognostic gene signatures in primary human mammary epithelial cells (HMECs). These analyses demonstrated that these factors frequently co–bind the promoters of genes, the expression of which is associated with a proliferative phenotype and poor patient outcome. These data suggest that these predicted MTRs do indeed drive the expression of gene signatures associated with poor patient outcome in breast cancer.
2015-09-30 | GSE62425 | GEO
Project description:Breast carcinoma (BC) is the leading cause of death in women worldwide, making up 23% of all cancers in women, with 1.38 million new cases worldwide annually and responsible for 460,000 deaths. Despite the significant advances in the identification of molecular markers and different modalities of treatment in primary BC, the ability to predict the metastatic behavior in breast cancer is still limited. The purpose of this study was to help identify novel molecular markers associated with clinical outcome in a cohort of Brazilian BC patients. We generated global gene expression profiles from 24 patients with invasive ductal BC followed for ≥ 5-years, including 15 samples from patients classified as presenting good prognosis based on traditional markers and clinical criteria and 9 patients that developed metastasis. We identified a set of 58 differentially expressed genes (p ≤0.01) between groups of patients with good and poor prognosis. Up-regulation of B3GNT7, PPM1D, TNKS2, PHB and GTSE1 in patients with poor prognosis was confirmed by quantitative RT-PCR in an independent sample set from patients with BC (47 with good prognosis and 8 that presented metastasis). Expression of BAD protein was investigated by immunohistochemistry in 1276 BC samples and confirmed the reduced expression levels in metastatic cases observed in the oligoarray data. These findings point to novel prognostic markers that can distinguish breast carcinoma samples according to clinical course and progression of the disease.
2016-06-30 | GSE73383 | GEO
Project description:Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value. 6 samples of stroma surrounding invasive breast primary tumors; 6 matched samples of normal stroma. 6 samples of stroma surrounding invasive prostate primary tumors; 6 matched samples of normal stroma.
2011-03-31 | E-GEOD-26910 | biostudies-arrayexpress
Project description:As the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25 % of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.We sought to determine whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, fibroblasts underwent transcriptome profilingthrough bulk RNA seq and pathway analysis. DCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.
2023-03-31 | GSE228582 | GEO
Project description:GATA2 expression in endometrial serous carcinoma cells correlates with patient outcome. Depletion of GATA2 in patient-derived endometrial serous carcinoma cell lines correlates with invasive potential. As GATA2 is a transcription factor, we hypothesize that GATA2-dependent target genes normally suppress invasion in endometrial serous carcinoma.
2025-03-06 | GSE264610 | GEO
Project description:ChIP-seq on primary breast cancer tumor samples for Era, H3K4me3, H3K27me3. Patients had a poor or good outcome after aromatase inhibitor treatment. Differential binding patterns between good and poor outcome patients were identified for each marker, predicting response to treatment comparing ER, H3K4me3 and H3K27me3 patterns between two breast cancer patient populations
2013-12-05 | E-GEOD-40867 | biostudies-arrayexpress
Project description:Ductal carcinoma in situ (DCIS) is the most common type (80%) of non-invasive breast lesions in women. The lack of validated prognostic markers, limited patient numbers, and variable tissue quality have a significant impact on diagnosis, risk stratification, patient enrolment, and the results of clinical studies. Here, we performed label-free quantitative proteomics on 50 clinical formalin-fixed, paraffin embedded biopsies, validating 22 putative biomarkers from independent genetic studies. Our comprehensive proteomic phenotyping reveals more than 380 differentially expressed proteins and metabolic vulnerabilities, that can inform new therapeutic strategies for DCIS and invasive ductal carcinoma (IDC). Due to the readily druggable nature of proteins and metabolic enzymes or metabolism inhibitors, this study is of high interest for clinical research and pharmaceutical industry. To further evaluate our findings, and to promote the clinical translation of our study, we developed a highly multiplexed targeted proteomics assay for 90 proteins associated with cancer metabolism, RNA regulation and signature cancer pathways, such as PI3K/AKT/mTOR and EGFR/RAS/RAF.
2024-12-31 | PXD040782 | Pride
Project description:Tumor-associated macrophages (TAMs) are regulators of extracellular matrix (ECM) remodeling and metastatic progression, the main cause of cancer-associated death. We found that disabled 2 mitogen-responsive phosphoprotein (DAB2) is highly expressed in tumor-infiltrating TAMs and its genetic ablation significantly impairs lung metastasis formation. DAB2-expressing TAMs, mainly localized along the tumor invasive front, participate in integrin recycling, ECM remodeling and directional migration in a tridimensional matrix. DAB2+ macrophages escort the invasive dissemination of cancer cells by a mechanosensing pathway requiring the transcription factor Yes-Associated Protein. In human lobular breast and gastric carcinomas, DAB2+ TAMs correlated with a poor clinical outcome, identifying DAB2 as potential prognostic biomarker for cancer patient stratification. DAB2 is therefore central for the pro-metastatic activity of TAMs.
2020-07-13 | GSE152674 | GEO