Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Prognostic Values of Immune Landscape in Ras-Mutant Colorectal Cancer Peritoneal Metastases

ABSTRACT: The peritoneal metastasis (PM) in patients with colorectal cancer (CRC) associated with poor survival, especially in those with Ras mutations. However, knowledge on the mechanism of molecular biology in CRC peritoneal metastasis (CRCPM) is limited, and the impact of tumor immune microenvironment (TME) on PM pathogenesis and the prognosis of CRCPM remains unclear. Therefore, we characterized the TME of CRCPM and evaluated its potential diagnostic and prognostic values. This study involved 21 patients with metastatic CRC (mCRC), of whom 11 with CRCPM were classified into the experimental group and 10 with mCRC without PM (noCRCPM) were classified into the control group. Formalin-fixed and paraffin-embedded tissue of primary tumors from all patients was examined using the NanoString RNA sequencing system. The clinicopathological variables and TME biomarkers were compared using the chi-square test and Cox regression analysis. According to the results of multivariate analysis, a prognostic nomogram was generated, and its prediction ability was measured using the concordance index (C-index). Survival curves were generated using the Kaplan–Meier method, and survival comparison between groups was conducted using the log-rank test.

ORGANISM(S): Homo sapiens

PROVIDER: GSE198085 | GEO | 2022/10/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Gene chip (Clariom S) analysis of 12 corresponding pairs of TECs and NECs from human colorectal carcinoma patients from different prognostic TMEs (Th1-TME vs Control-TME)

Project description:Tumor endothelial cells (TECs) and corresponding normal endothelial cells (NECs) were isolated from 12 different human colocrectal carcinoma (CRC) patients with different prognostic tumor microenvironments (TME: Th1-TME vs Control-TME).

2023-05-01 | E-MTAB-10465 | biostudies-arrayexpress

Tailoring heated intra-peritoneal Mitomycin C for peritoneal metastases originating from colorectal carcinoma – A translational approach to improve survival

Project description:Patients with peritoneal metastases (PM) originating from colorectal carcinoma (CRC) are curatively treated by cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C (MMC). We aim to improve patient selection and personalize treatment for patients treated with HIPEC by predicting MMC sensitivity. MMC sensitivity was determined for 12 CRC cell lines using two separate assays. Thirty-seven genes related to the FA-BRCA pathway, ATM-ATR pathway and enzymatic activation of MMC were correlated on expression array platform to MMC sensitivity. Low sensitivity correlated with a decrease in BLM (p=0.01) and BRCA2 (p=0.02) on mRNA expression level. Both genes are part of the Fanconi Anaemia-BRCA (FA-BRCA) pathway and therefore, functionality of the FA-BRCA pathway in cell lines was determined using chromosomal breakage assay and Western Blot for key protein FANCD2. However, FA-BRCA pathway functionality showed no correlation to MMC sensitivity. BLM was further analysed by staining for the corresponding protein with immunohistochemistry (IHC) on both CRC cell lines and patient material. In cell lines, weak intensity staining by IHC correlated to high sensitivity (p=0.04) to MMC. High BLM protein expression was significantly correlated to a decreased survival in patients after CRS and HIPEC (p=0.04). We are the first to have found a possible predictive biomarker for PM with CRC.

2015-12-01 | GSE50494 | GEO

Peritoneal Metastases from Colorectal Cancer belong to Consensus Molecular Subtype 4 and are sensitized to oxaliplatin by inhibiting reducing capacity

Project description:Background: Peritoneal metastases (PM) in colorectal cancer (CRC) are associated with therapy resistance and poor survival. Oxaliplatin monotherapy is widely applied in the intraperitoneal treatment of PM, but fails to yield clinical benefit. We aimed to identify the mechanism(s) underlying PM resistance to oxaliplatin and to develop strategies overcoming such resistance. Experimental design: We generated a biobank consisting of 35 primary tumor regions and 59 paired PM from 12 patients. All samples were analyzed by RNA sequencing. We also generated a series of PM-derived organoid (PMDO) cultures and used these to design and test strategies to overcome resistance to oxaliplatin Results: PM displayed various hallmarks of aggressive CRC biology. The vast majority of PM and paired primary tumors belonged to the Consensus Molecular Subtype 4 (CMS4). PMDO cultures were resistant to oxaliplatin and expressed high levels of glutamate-cysteine ligase (GCLC) causing detoxification of oxaliplatin through glutathione synthesis. Genetic or pharmacological targeting of GCLC sensitized PMDOs to a 1-hour exposure to oxaliplatin, through increased platinum-DNA adduct formation Conclusions: These results link oxaliplatin resistance of colorectal PM to their CMS4 status and high reducing capacity. Inhibiting the reducing capacity of PM may be an effective strategy to overcome PM resistance to oxaliplatin

2022-06-15 | GSE190609 | GEO

Characterization of cell-type specific circular RNAs associated with colorectal cancer metastasis

Project description:Colorectal cancer (CRC) is the most common gastrointestinal malignancy in the U.S.A. and approximately 50% of CRC patients develop metastatic disease (mCRC) with an average 5-year survival rate of 13%. Despite our understanding of circular RNAs (circRNAs) in primary cancer, their role throughout mCRC remains poorly characterized. Further, despite the availability of bulk RNA-Seq data for monitoring circRNA expression little is known about their cell-type specific expression profiles to fully understand their functions between tumor cells and the microenvironment. To evaluate circRNAs in mCRC progression, total RNA-Seq was performed on 30 matched normal, primary, and distant metastatic samples from 14 mCRC patients. Additionally, the transcriptome of five CRC cell lines were sequenced to construct a circRNA catalog in CRC. Differential expression (DE) analysis identified circRNAs dysregulated between normal, primary, and metastatic tissues. Differential backsplicing (DS) analysis was used to highlight circRNAs with an altered tendency in backsplicing as compared to their linear counterparts. Cell-type deconvolution was performed using published CRC single-cell RNA-Seq datasets as signature matrices. The cell-type specific expression of circRNAs was then estimated through a non-negative least squares statistical model.

2023-05-04 | GSE221240 | GEO

Novel prognostic implications of complement activation in the tumor microenvironment for de novo metastatic BRAF V600E mutant colorectal cancer

Project description:Prognosis of metastatic BRAF V600E mutant colorectal cancer (CRC) is poor, and the prognostic implications of immune contextures in the tumor microenvironment (TME) for CRC remain elusive. Complement activation in the TME was significantly associated with poor OS and was correlated with TAM M2 in patients with de novo metastatic BRAF V600E mutant CRC.

2022-11-08 | GSE211576 | GEO

Methylation analysis of 12 corresponding pairs of TECs and NECs isolated from human CRC patients with different prognostic TMEs

Project description:Methylation analysis of 12 corresponding pairs of tumor endothelial cells (TECs) and normal endothelial cells (NECs) isolated from human colorectal carcinoma (CRC) patients with different prognostic tumor microenvironments (TMEs: Th1-TME vs Control-TME): High and low GBP-1 expression in the tumors detected by IHC was used to categorize the patient-derived cells into Th1-TME and Control-TME (compare Naschberger et al, J Clin Invest 2016 and Naschberger et al, Int J Cancer 2008). Isolation of the samples was done according to Naschberger et al, JoVE 2018. The analysis is paralleled by omics-analysis of the same cell cultures at the transcriptome (E-MTAB-10465) and genome level (E-MEXP-3993).

2023-05-01 | E-MTAB-10467 | biostudies-arrayexpress

Transcriptomics and proteomics reveal distinct biology for lymph node metastases and tumor deposits in colorectal cancer

Project description:Objective: Both lymph node metastases (LNMs) and tumor deposits (TDs) are included in colorectal cancer (CRC) staging, although knowledge regarding their biological background is lacking. This study aims to compare the biology of these prognostic features, which is essential for a better understanding of their role in CRC spread. Design: Spatially resolved transcriptomic analysis using Digital Spatial Profiling was performed on TDs and LNMs from 10 CRC patients using 1,388 RNA targets, for the tumor cells and tumor microenvironment (TME). Shotgun proteomics identified 5,578 proteins in 12 different patients. Differences in RNA and protein expression were analyzed, and spatial deconvolution was performed. Image-based CMS (imCMS) analysis was performed on all TDs and LNMs included in the study. Results: Transcriptome and proteome profiles identified distinct clusters for TDs and LNMs in both the tumor and TME segment, with upregulation of matrix remodeling, cell adhesion/motility and epithelial mesenchymal transition (EMT) in TDs (all p<0.05). Spatial deconvolution showed a significantly increased number of fibroblasts, macrophages, and regulatory T cells (p<0.05) in TDs. In consistency with a higher fibroblast and EMT component, imCMS classified 62% of TDs as poor prognosis subtype CMS4 compared to 36% of LNMs (p<0.05). Conclusion: Compared to LNMs, TDs have a more invasive state; involving a distinct TME and upregulation of EMT, which are reflected in a more frequent histological classification of TDs as CMS4. These results emphasize the heterogeneity of locoregional spread the fact that TDs should merit more attention both in future research and during staging.

2023-09-19 | PXD041625 | Pride

Mucosal biopsies from groups Normal (NOR) and patients who underwent curative large bowel resection for colorectal cancer (M-CRC)

Project description:The challenge of preventing colorectal cancer (CRC) is the early identification of individuals whose apparently normal colorectal mucosa will develop cancer, because of inherited trait or environmental exposure. We sought to use genome-wide expression profiling of endoscopic biopsies to detect a signature of propensity for cancer. We performed oligonucleotide microarray analysis of normal appearing mucosa of the following cases: healthy individuals (NOR), disease-free carriers predisposed to HNPCC (hereditary non-polyposis CRC), disease-free patients who underwent curative large bowel resection for CRC 1 to 15 years earlier and patients with CRC (MCRC) (GSE23011). As test set we run on affymetrix arrays an independent set of mucosal biopsies of MCRC and NOR samples. This profiling is based on the analysis of 5 patients who underwent curative large bowel resection for CRC from 1 to 15 years before (MCRC samples), and 12 endoscopy-negative, asymptomatic individuals (NOR samples)

2013-11-30 | E-GEOD-23194 | biostudies-arrayexpress

Inactivation of interferon signaling promotes the establishment of an immunosuppressive microenvironment in colorectal cancers

Project description:Tumors arise and grow despite anti-cancer immune responses. These responses can be stimulated by immunotherapies such as immune checkpoint inhibitors (e.g. anti-PD1 antibodies) and chimeric antigen receptors (CAR). Efficacy of these agents in solid tumors including colorectal cancers (CRC) is limited by immunosuppressive tumor microenvironment (TME) that prevents killing of malignant cells by cytotoxic T lymphocytes (CTL). Understanding the nature of TME-generated immunosuppression is of paramount importance. Here we report that TME elicited immunosuppression via eliminating activated CTL; this elimination required TME stress-induced downregulation of the IFNAR1 chain of type I interferon (IFN) receptor and attenuation of its signaling. Downregulation of IFNAR1 was observed in human colorectal cancers (CRC) and in mouse CRC models where it was required for efficient tumor development and progression. Stabilization of IFNAR1 on CTL improved their survival and increased anti- tumor activities of CAR T cells and PD1 inhibitors thereby providing a rationale for targeting IFNAR1 degradation for immunotherapies optimization. Two genotypes of mice were examined either 9 or 21 days post injection of MC38 colon cancer cells or MC38mRFP cells, respectively. 2-3 replicate mice were analyzed on separate arrays for each condition. 6 conditions in total were analyzed.

2016-01-15 | E-GEOD-76889 | biostudies-arrayexpress

Exploiting a subtype-specific mitochondrial vulnerability for successful treatment of colorectal peritoneal metastases

Project description:Peritoneal metastases (PM) in colorectal cancer (CRC) present a significant challenge due to limited treatment options and poor patient prognosis. While cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) offers curative potential for selected patients, its overall benefit remains limited compared to surgery alone. In this study we show that the majority of CRC-PM represent the CMS4-subtype. Despite CRS-HIPEC treatment, CMS4 patients had high rates of recurrent disease and mortality, indicating limited effectiveness of the treatment. To explore alternative treatment approaches, we queried large-scale compound screens and discovered the copper (Cu)-ionophore elesclomol (ES) as a highly effective agent against CMS4-specific disease models. ES exhibited rapid and selective cytotoxicity against CMS4 cells by targeting the oxidative phosphorylation machinery. CMS4 cells had reduced absolute mitochondrial content and lower expression of genes involved in oxidative phosphorylation, making them vulnerable to ES-induced cytotoxicity. Short exposures to ES combined with Cu (ES-Cu) resulted in near-complete growth inhibition of cancer cells, suggesting its potential for HIPEC-like intra-abdominal treatment procedures. Furthermore, ES-Cu demonstrated efficacy in preclinical models of PM, including CRC-PM and ovarian cancer organoids, and a HIPEC rat model of PM. These findings highlight ES-Cu as promising candidate for the local treatment of CRC-PM, with broader implications for other cancer types characterized by high incidence of PM.

2024-05-01 | GSE242676 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data