A cause-and-effect relationship between biomarkers and risk of colorectal cancer progression: a Mendelian randomised and retrospective nested case-control study
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 113689 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Introduction: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.<br><br>Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n=29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n=35) consisted of a random sample of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. miRNA profiling was performed using formalin-fixed, paraffin-embedded tumors. Biomarkers related to metastatic potential were identified independent of clinical stage, and a cutoff point was selected based on the optimal sensitivity and specificity (ROC curve). Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential. <br><br>Results: miRNA expression profiling identified several miRNAs that were either specific and shared across all clinical stages (p?0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family), cell proliferation and invasion (hsa-miR-16 and has-miR-205) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were up-regulated in metastatic cases of CSI and II. Furthermore, the combination of the 3 miRNAs identified for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs. <br><br>Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.
2013-08-07 | E-MEXP-3947 | biostudies-arrayexpress
Project description:The purpose of this study was to improve prediction of patients at high-risk for metastatic disease utilizing a nested case-control design that uniquely enables enrichment for relevant phenotypes. We identified all women diagnosed with primary breast cancer from January 1, 1997, to December 31, 2005, in the Stockholm health care region. Patients developing distant metastatic disease (cases) were selected and controls (free from distant disease) were randomly matched by adjuvant therapy, age and calendar period at diagnosis. The nested case-control study included 768 study subjects with clinical information and gene expression arrays (Human Cancer G110). Study subjects were randomly and equally divided into training set (discovery) or testing (validation) set. Metastatic onset prediction was then compared including either clinical variables only or combining clinical and genetic information. Differentially expressed genes and pathways between cases and controls included a wide-spectrum of well known as well as candidate regulators of the metastatic cascade. The nested case-control study included 768 study subjects corresponding to 623 primary tumor samples. Details concerning case-control status are given in the samples section. Each case and its' matching controls form risk sets, indicated by the setnr variable.
2014-11-03 | E-GEOD-48091 | biostudies-arrayexpress
Project description:The purpose of this study was to improve prediction of patients at high-risk for metastatic disease utilizing a nested case-control design that uniquely enables enrichment for relevant phenotypes. We identified all women diagnosed with primary breast cancer from January 1, 1997, to December 31, 2005, in the Stockholm health care region. Patients developing distant metastatic disease (cases) were selected and controls (free from distant disease) were randomly matched by adjuvant therapy, age and calendar period at diagnosis. The nested case-control study included 768 study subjects with clinical information and gene expression arrays (Human Cancer G110). Study subjects were randomly and equally divided into training set (discovery) or testing (validation) set. Metastatic onset prediction was then compared including either clinical variables only or combining clinical and genetic information. Differentially expressed genes and pathways between cases and controls included a wide-spectrum of well known as well as candidate regulators of the metastatic cascade.
2015-07-08 | GSE48091 | GEO
Project description:This is a quality control (QC) substudy of GSE48091. The QC substudy comprises gene-expression profiling of re-extracted tumor RNA for a subset of the tumours in the full study. As background, a population-based cohort study of metastatic breast cancer patients was first designed. Thereafter, a case-control study nested in the corresponding population-based cohort of primary breast cancer patients was designed by selecting distant metastasis-free controls to each case. Tumor RNA was extracted in the same order. All RNA was profiled on microarrays in randomized order. For quality control, RNA was also re-extracted (new tumor piece) in a randomized order for randomly selected cases-controls sets and profiled with the rest. Keywords: Expression profiling by array The nested case-control study included 768 study subjects corresponding to 623 primary tumor samples. This QC substudy comprises 97 of the study subjects (all different primary tumor samples). Details concerning case-control status are given in the samples section. This Series includes a re-analysis of 97 samples from GSE48091. The file "full_data_matrix.txt" includes the re-normalized values for the 97 samples from GSE48091 and the normalized values for the 97 new samples from the same patients that were analyzed together.
2016-05-28 | E-GEOD-81954 | biostudies-arrayexpress
Project description:The microbial communities residing in the child gut are thought to play an important role in child growth, although the relationship is not well understood. We examined a cohort of young children from Mirzapur, Bangladesh, prospectively over 18 months. Four fecal markers of environmental enteropathy (EE) (high levels of alpha-1-antitrypsin, calprotectin, myeloperoxidase, and neopterin) were examined and anthropometric measures obtained from a cohort of 68 children. The 16S rRNA gene of bacterial DNA was sequenced from stool samples and used to estimate amplicon sequence variants (ASVs). We age-matched children with poor growth to children with normal growth within 1 month and compared the change in abundance and diversity of ASVs over time. Elevated EE markers and poor linear growth in children were associated with changes in microbial communities in the gut. There were increased amounts of Escherichia/Shigella and Proteobacteria and decreased amounts of Prevotella associated with poorly growing children consistent with the mounting evidence supporting the relationship between intestinal inflammation, child growth, and changes in gut microbiota composition. Future research is needed to investigate this association among young children in low- and middle-income countries.
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Project description:BACKGROUND:Differentiating cerebral malaria (CM) from other causes of serious illness in African children is problematic, owing to the non-specific nature of the clinical presentation and the high prevalence of incidental parasitaemia. CM is associated with endothelial activation. In this study we tested the hypothesis that endothelium-derived biomarkers are associated with the pathophysiology of severe malaria and may help identify children with CM. METHODS AND FINDINGS:Plasma samples were tested from children recruited with uncomplicated malaria (UM; n?=?32), cerebral malaria with retinopathy (CM-R; n?=?38), clinically defined CM without retinopathy (CM-N; n?=?29), or non-malaria febrile illness with decreased consciousness (CNS; n?=?24). Admission levels of angiopoietin-2 (Ang-2), Ang-1, soluble Tie-2 (sTie-2), von Willebrand factor (VWF), its propeptide (VWFpp), vascular endothelial growth factor (VEGF), soluble ICAM-1 (sICAM-1) and interferon-inducible protein 10 (IP-10) were measured by ELISA. Children with CM-R had significantly higher median levels of Ang-2, Ang-2:Ang-1, sTie-2, VWFpp and sICAM-1 compared to children with CM-N. Children with CM-R had significantly lower median levels of Ang-1 and higher median concentrations of Ang-2:Ang-1, sTie-2, VWF, VWFpp, VEGF and sICAM-1 compared to UM, and significantly lower median levels of Ang-1 and higher median levels of Ang-2, Ang-2:Ang-1, VWF and VWFpp compared to children with fever and altered consciousness due to other causes. Ang-1 was the best discriminator between UM and CM-R and between CNS and CM-R (areas under the ROC curve of 0.96 and 0.93, respectively). A comparison of biomarker levels in CM-R between admission and recovery showed uniform increases in Ang-1 levels, suggesting this biomarker may have utility in monitoring clinical response. CONCLUSIONS:These results suggest that endothelial proteins are informative biomarkers of malarial disease severity. These results require validation in prospective studies to confirm that this group of biomarkers improves the diagnostic accuracy of CM from similar conditions causing fever and altered consciousness.
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Project description:The association between vaginal microbiota composition and miscarriage: a nested case-control study
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Project description:Expression profiles of colorectal liver metastasis samples collected from Paul Brousse Hospital (France) and University Hospital Utrecht (The Netherlands). Patients are divided into a high-risk (DFS < 1 year) and a low-risk group (DFS < 1 year).
2012-11-29 | E-TABM-1112 | biostudies-arrayexpress
Project description:Clinically isolated syndrome (CIS) refers to the earliest clinical manifestation of multiple sclerosis (MS). Currently there are no prognostic biological markers that accurately predict conversion of CIS to clinically definite MS (CDMS). Furthermore, the earliest molecular events in MS are still unknown. We used microarrays to study gene expression in naïve CD4+ T cells from 37 CIS patients at time of diagnosis and after one year. Supervised machine-learning methods were used to build predictive models of disease conversion. We identified 975 genes whose expression segregated CIS patients into 4 distinct subgroups. A subset of 108 genes further discriminated patients from one of these (group#1) from other CIS patients. Remarkably, 92% of patients from group #1 converted to CDMS within 9 months. Consistent downregulation of TOB1, a critical regulator of cell proliferation, was characteristic of group #1 patients. Decreased TOB1 expression at the RNA and protein levels was also confirmed in experimental autoimmune encephalomyelitis (EAE). Finally, a genetic association was observed between TOB1 variation and MS progression in an independent cohort. These results indicate that CIS patients at high risk of conversion have impaired regulation of T cell quiescence resulting in earlier activation of pathogenic CD4+ cells. Keywords: Disease state: CIS (Clinically Isolated Syndrome - Multiple Sclerosis) versus control. Time series: some patients and controls were resampled approximately one year later
2008-11-26 | GSE13732 | GEO