Relapse Markers for Colorectal Cancer
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer,Colorectal Neoplasms
PROVIDER: 2380153 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
Similar Datasets
Project description:To explore the possibility that DNAm-derived biological age is associated with mortality independently of common risk factors in subjects with type 2 diabetes (T2D), we leveraged a well-characterized cohort of individuals with T2D and followed-up for 16.8 years to create two groups, one of deceased individuals and the other of survived patients, fully matched for common risk factors. We performed a genome wide DNAm analysis of peripheral blood leukocytes to explore differentially methylated genes related to death in T2D, test the ability of a chosen set of existing tools estimating biological aging from DNAm to predict mortality, and assess the differences between deceased and survived diabetic patients in DNAm-inferred levels of selected inflammatory proteins and in predicted blood cell counts with a known pathophysiological role in T2D.
2024-07-05 | E-MTAB-14228 | biostudies-arrayexpress
Project description:Purpose: The benefit of postoperative adjuvant chemotherapy in patients with Dukes´ B colorectal cancer is still uncertain and its routine use is not recommended. The five years survival rate is approximately 75% and identification of the patients at high risk of recurrence would represent an important strategy for the use of adjuvant chemotherapy. In this study we identify new prognostic markers for tumor relapse in Dukes´ B colon cancer patients. Patients and Methods: We retrospectively analyzed gene expression profiles in frozen tumor specimens from 16 patients with Dukes´ B colorectal cancer by using high density oligonucleotide microarrays. Data were normalized and subsequently analyzed with two different statistical procedures. The intensity value associated to each spot is the result of subtracting a gaussian function of the noise from the foreground values {Kooperberg, 2002}. After this background subtraction, base 2 logarithms of all data were calculated and genes with more than two missing values were excluded from the analysis. The remaining missing values were replaced by using the KNN imputation method {Troyanskaya, 2001}. The great number of genes present in the microarray allowed us to consider that the overall fluorescence intensity must be the same for all slides, as the vast majority of genes will not change their expression between the two conditions tested. So we used the quantile normalization method {Bolstad, 2003}, which equalizes not only the average intensity but also the range of intensity values between slides. We decided to use two different statistical procedures in the search of significant differences in gene expression between the relapsed and non-relapsed patients. Only the genes selected by both statistical procedures were considered as differentially expressed between relapsed and non-relapsed patients. The first test was a permutation t-test for comparison of two means {Dudoit, 2003} and the second one a variation of the Fisher test based on the work presented by Iizuka et al. {Iizuka, 2003} in which they searched for the optimal number of genes that could differentiate between two groups of samples. Briefly, we used the same algorithms for the calculation of the Fisher criterion, but instead of looking for the optimal subset of genes able to differentiate between groups, what requires a lot of computing capacity, we tried different numbers of candidate genes and selected a number which yielded very good classification results when evaluated by means of Fast ICA {Lee, 2003} and Hierarchical Clustering {Everitt, 1974}. The procedure consisted of selecting the 30 genes with the highest Fisher criterion value in 6 rounds of iteration, each round leaving one sample of the relapsed group and two of the non-relapsed group out of the calculations (a variant of the “leave one out” method). We selected the genes present in at least 3 of the iterations. The intersection of the groups of genes selected by the two statistical procedures was selected as a prognostic signature for relapse in Dukes´stage B colon cancer. Results: Our results show a group of 48 genes differentially expressed between the relapsed and non-relapsed groups with an associated probability below 0,001 in the t test. Another statistical procedure based on the Fisher criterion resulted in 11 genes able to separate both groups. In order to minimize false positives we only considered a good gene signature the 8 genes selected by both statistical procedures. These genes are ribosomal protein S5, chromodomain helicase DNA binding protein 2, lysosomal ATPase V0 subunit A isoform 1, zinc finger protein 148, brain protein I3 (BRI3), hypothetical protein MGC23401 and one unknown clone. In order to verify the obtained results, the differential expression of the first two genes was confirmed by real time PCR. Keywords: repeat sample
2005-05-07 | GSE2630 | GEO
Project description:Purpose: ME/CFS is a debilitating and complex disease. The majority of patients exist in a chronic state of health where they are affected by relapse events. Precision medicine following patients can capture changes in the DNA methylation indicative of biological dysfunction Methods: DNA was extracted from the PBMCs of 2 ME/CFS patients and a age/gender matched control at five different time points. After performing RRBS the sequence was aligned to hg19 genome using Bismark. The data was analyzed using a Chi squared test through DMAP in order to determine variation between the patient and control groups across 40-220bp fragments of the genome. Results: A total of 17 and 14 statistically significant variably methylated fragements were indentified in each patient that strongly associated with a relapse event. These fragements were found on regions of regulatory importance of the genome that associated with immune (primarily inflammatory) and metabolic function. Conclusions: Our study represents the first investigation of ME/CFS patients using reduced representation bisulfite sequencing along a longitudinal timeframe. We captured a number of major variably methylated fragments in each patient that associated with their relapse events. Our results identified a number of differentially methylated regulatory elements and gene bodies that highlight the disturbed pathophysiology in ME/CFS. DNA methylation that differentiates disease variability in ongoing ME/CFS may have practical applications for strategies to deacrease the frequency and severity of relapse events.
2021-02-11 | GSE166592 | GEO
Project description:We investigated the individual phenotypic predisposition to developing uncomplicated infection or sepsis in a large cohort of non-infected patients undergoing major elective surgery. We built machine learning classification models on preoperative transcriptomic signatures to predict postoperative outcomes including sepsis. To test the predictive capability of these models for ongoing infection, whole blood RNA sequencing analysis on 61 independent patients with COVID-19 (10 mild, 51 severe cases) was performed.
2024-08-30 | GSE208587 | GEO
Project description:Non-invasive detection of aberrant DNA methylation could provide invaluable biomarkers for earlier detection of triple negative breast cancer (TNBC) which could help clinicians for easier and more efficient treatment options. We evaluated genome-wide DNA methylation data derived from TNBC and normal breast tissues, peripheral blood of TNBC cases and controls, and reference samples of sorted blood and mammary cells. Differentially methylated regions (DMRs) between TNBC and normal breast tissues were stringently selected, verified, and externally validated. A machine learning algorithm was applied to select the top DMRs, which then were evaluated on plasma-derived circulating cell-free DNA (cfDNA) samples of TNBC patients and healthy controls. We identified 23 DMRs accounting for the methylation profile of blood cells and reference mammary cells and then selected six top DMRs for cfDNA analysis. We quantified un-/methylated copies of these DMRs by droplet digital PCR analysis in a plasma test set from TNBC patients and healthy controls and confirmed our findings obtained on tissues. Differential cfDNA methylation was confirmed in an independent validation set of plasma samples. A methylation score combining signatures of the top three DMRs overlapping with the SPAG6, LINC10606, and TBCD/ZNF750 genes had the best capability to discriminate TNBC patients from controls (AUC=0.74 in test set and AUC=0.77 in validation set). Our findings demonstrate the usefulness of cfDNA-based methylation signatures as non-invasive liquid biopsy markers for diagnosis of TNBC.
2022-11-23 | GSE207998 | GEO
Project description:Two matched groups of Heart Failure with reduced ejection fraction patients with no peripheral venous congestion were studied: with recent prior heart failure hospitalization vs. without recent heart failure hospitalization. Peripheral venous congestion was modeled by inflating a cuff around the dominant arm, targeting an ~30mmHg increase in venous pressure (venous stress test). Blood and endothelial cells were sampled before and after 90 minutes of venous stress test.
2023-08-28 | GSE237856 | GEO
Project description:Background Identification of patients at risk of tuberculosis relapse following treatment would revolutionize clinical trials of new drugs and regimens and facilitate clinical management. The study aim was to determine whether tuberculosis patients who subsequently suffer relapse have different immune responses to mycobacteria in vitro compared to patients who remain cured for two years post-treatment. Methods First episode pulmonary tuberculosis patients were recruited into a surrogate marker study in Cape Town, South Africa. Peripheral blood samples were collected at diagnosis and after two and four weeks of tuberculosis treatment. Diluted blood was cultured with live Mycobacterium tuberculosis for six days and cellular RNA was frozen. Gene expression in samples from ten patients who subsequently relapsed, confirmed by stain genotyping, was compared to those who remained cured using Affymetrix microarrays. Results At diagnosis, the expression of 668 genes was significantly different in samples from patients who subsequently relapsed compared to successfully cured patients, and these differences persisted for at least four weeks. Gene Ontology and biological pathways analyses revealed the most significant difference was up-regulation of genes involved in cytotoxic cell-mediated killing, such as perforin, granulysin and fas ligand. Results were confirmed by qRT-PCR in a wider patient cohort. Conclusions These data show that patients who will subsequently relapse exhibit altered immune responses at diagnosis, including excessively robust cytolytic responses to M. tuberculosis in vitro, compared to patients who will achieve durable cure. Together with microbiological and clinical indices, these differences could be exploited for patient stratification in drugs trials, or for host-directed therapy development.
2015-09-10 | GSE67589 | GEO
Project description:Traditional Chinese medicine emphasizes treatment based on syndrome differentiation. This study aimed to clarify the characteristics of DNA methylation expression profiles in peripheral blood mononuclear cells in patients with psoriasis and analyze the differences in these profiles among different traditional Chinese medicine syndromes of psoriasis in order to provide a material basis for the diversity of these syndromes. Blood samples were collected from 32 participants, including 13 patients with psoriatic blood heat syndrome, 13 patients with psoriatic blood stasis syndrome, and 6 healthy controls. Peripheral blood mononuclear cells were extracted and subjected to DNA quality inspection. An Illumina Human Methylation 850k chip was used to sequence each group of samples. After screening out differentially methylated sites, the distribution of the corresponding differentially methylated genes on the chromatin was determined. According to gene annotation classification and CpG island annotation classification, the differentially methylated regions between sample groups were screened, and Gene Ontology and KEGG pathway analyses were used to perform functional analysis of differentially methylated genes. Finally, the differentially methylated genes closely correlating with psoriasis severity were screened using Spearman’s correlation analysis.
2022-10-05 | GSE183608 | GEO
Project description:7 male OUD patients and 7 male health controls with demographic and clinical data matched were enrolled in this study. rRNA removed library and small RNA library were constructed using peripheral blood RNA. RNA-seq was used to investigate the peripheral transcriptomic changes between the two groups.
2022-05-31 | GSE198122 | GEO
Project description:7 male OUD patients and 7 male health controls with demographic and clinical data matched were enrolled in this study. rRNA removed library and small RNA library were constructed using peripheral blood RNA. RNA-seq was used to investigate the peripheral transcriptomic changes between the two groups.
2022-05-31 | GSE198121 | GEO