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Epigenetic clonality confers por prognosis in colorrectal cancer patients (FOLFIRI)

ABSTRACT: In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found. Cohort of CRC patients (N=17) who recieved quemotherapy (FOLFIRI)

ORGANISM(S): Homo sapiens

PROVIDER: GSE81472 | GEO | 2016/08/16

SECONDARY ACCESSION(S): PRJNA321734

REPOSITORIES: GEO

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Epigenetic clonality confers por prognosis in colorrectal cancer patients (first study)

Project description:In CRC, 1) to identify epigenetic changes at inter-tumor and intra-tumor level, and 2) to relate intra-tumor clonality to clinical, molecular and histopathologic parameters. From 79 FFPE tumors, 3 different regions were macrodissected: invasive front (IF), digestive tract surface (DTS) and central bulk (CB). Clinical, molecular, and histopathologic parameters were stablished. Epigenetic analysis was performed using Infinium 450K beadchip (Illumina) and R statistics. Intra-tumor regions clustered together by patient. The biggest epigenetic changes were in IF vs DTS/CB. By patient, the most often divergent region was IF (49.4%) comparing with DTS and CB (25.3% in both). It did not correlate with histopathologic, molecular and clinical parameters.Epigenetic clonality is higher at intra-tumor level. The highest changes are observed in IF vs DTS/CB. No association with histopathologic, molecular, and clinical characteristics was found.

2016-08-16 | GSE69550 | GEO

Epigenetic clonality confers por prognosis in colorrectal cancer patients (technical replicates)

2016-08-16 | GSE81359 | GEO

Epigenetic clonality confers por prognosis in colorrectal cancer patients (SNP)

2016-08-16 | GSE81362 | GEO

Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties

Project description:T cell responses within pediatric brain tumors (PBT) remain poorly understood. We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived brain tumor-infiltrating T cells to map T cell molecular profile with TCR repertoire and clonality. We demonstrate marked clonal expansion of intra-tumoral T cells and reveal their differential phenotype, transcriptional state and functional properties within brain tumors. To understand T cell responses within highly immunogenic tumors that respond to checkpoint blockers, we undertook analysis of human non-small cell lung cancer (NSCLC). We performed single-cell RNA-seq (scRNA-seq) and paired T cell receptor sequencing (TCR-Seq) of patient-derived lung tumor-infiltrating T cells to map T cell molecular profile with clonality.

2024-01-16 | GSE221776 | GEO

Proteomic analysis reveals the role of ARID1A in regulating the Wnt signaling pathway in colon cancer cells

Project description:The AT-rich interacting domain-containing protein 1A (ARID1A) is a tumor suppressor gene that has been implicated in various cancers, including colorectal cancer (CRC). The present study employed a proteomic approach to uncover the molecular mechanisms of ARID1A in CRC carcinogenesis.

2024-05-21 | PXD052413 | JPOST Repository

Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers

Project description:Purpose: Small bowel adenocarcinoma (SBA) is a rare cancer and consequently the number of clinical trials has been very limited due to the small numbers of patients. Chemotherapy regimens are currently rather arbitrarily chosen between either a colorectal (CRC) or a gastric cancer (GC) regimen. Chromosomal copy number aberrations are a hallmark of solid tumours and can be measured by array comparative genomic hybridization (aCGH). The aim of the present study is to investigate whether genome-wide copy number aberrations of SBA are more similar to CRC or GC in order to support treatment of SBA according to either regimen. Experimental Design: A total of 85 GCs, CRCs and SBAs were selected from existing in house aCGH datasets based on array quality and clinical parameters. Differences and similarities in gains and losses of the three tumor types were analyzed using supervised and unsupervised analysis. Results: Hierarchical clustering revealed substantial overlap of chromosomal copy number profiles between SBA and CRC and less overlap between SBA and GC. Chromosome 13q13.2-q31.3 is primarily gained in SBA and CRC and the strongest feature discriminating SBA from GC. Further strong discriminating copy number characteristics are aberrations at chromosomes 1p36.3-p34.3, 4p15.3-q35.2, 9p24.3-p11.1 and 17p13.3-p13.2. Conclusions: SBA is more similar to CRC than to GC, based on genome-wide copy number aberrations. These data provide molecular support for treatment of SBA according to a CRC regimen. 29 gastric adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control samples, 29 colorectal adenocarcinomas on 5K or 6K BAC arrays of which 2 samples are also done on 30K oligonucleotide arrays as control, 27 small bowel adenocarcinomas done on 30K oligonucleotide arrays of which 2 samples are also done on 5K BAC arrays as control.

2011-06-13 | E-GEOD-23418 | biostudies-arrayexpress

Transcription profiling by array of microsatellite stable stage III Colorectal Adenocarcinoma (MSS-CRC) with wild type or mutant p53 to study the prognostic significance of the mutation

Project description:Clinical Significance: Understanding the differences in colorectal cancer (CRC) aggressiveness and clinical outcomes in relation to tumor stage and different molecular subsets is at most important for designing treatment regimens. However, molecular signatures for specific phenotypic subsets that predict the aggressiveness and clinical outcomes of CRC, specifically in advanced disease stage are lacking. Therefore, for the first time, the current study has identified a set of molecular markers that are associated with aggressive Stage III CRCs that exhibited microsatellite stable and mutant p53 phenotypic features. These findings might aid in designing aggressive treatment regimens and help to provide insights into the development of novel therapeutic targets. Results: Increased incidence of p53 mutations in MSS CRCs (58%) was associated with higher CRC-specific mortality than MSS-p53 wild-type phenotypes (log-rank, P=0.025; and hazard ratio, 2.52; 95% confidence interval, 1.25-5.08). Of 49 down-regulated genes, LPAR6, PDLIM3 and PLAT and of 35 up-regulated genes, TRIM29, FUT3, IQGAP3, and SLC6A8, were confirmed by qNPA, qRT-PCR, and IHC platforms. Conclusions: p53 mutations are associated with poor prognosis of Stage III microsatellite stable CRCs. p53 wild type vs. mutant tumor samples

2012-01-26 | E-GEOD-27157 | biostudies-arrayexpress

Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

Project description:Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans

| PRJNA683217 | ENA

IFN gamma signaling in cytotoxic T cells restricts antitumor responses by inhibiting the maintenance and clonality of intra-tumoral stem-like T cells

Project description:IFN gamma signaling in cytotoxic T cells restricts antitumor responses by inhibiting the maintenance and clonality of intra-tumoral stem-like T cells

2022-12-16 | GSE221118 | GEO

Functional states in tumor-initiating cell differentiation in human colorectal cancer

Project description:Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell mRNA-sequencing (scRNA-seq) of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Targeting transcriptional states associated to cancer cell differentiation might unravel vulnerabilities in human CRC.

2021-05-07 | PXD018230 | Pride

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