Systematic screening of prognostic and recurrence markers of colorectal cancer and construction of survival prediction model
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2703941 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Albeit responding well to therapy, estrogen receptor positive breast cancers frequently become subsequently resistant. This leads to distant metastasis and release of circulating tumor cells (CTCs) into the blood stream and ends with the death of the patient. Here we analyzed the proteome of CTC-ITB-01 by mass spectrometry and quantified 7954 different proteins using MCF-7 as a reference proteome. The data were deposited in a database for public access. CTC-ITB-01 is a CTC cell line derived from a patient with metastatic and estrogen receptor alpha (ER-alpha) positive breast cancer. We found remarkable high levels of the protein sushi domain-containing protein 2 (SUSD2) in CTC-ITB-01. Presence of SUSD2 in CTC of patients with breast cancer was confirmed by CellSearch (9/23 CTC positive cases). Ectonucleotide pyrophosphatase /phosphodiesterase family member 1 (ENPP1) was detected in CTC-ITB-01 and confirmed in CTC of breast cancer patients (n=3). ENPP1 can mediate immune evasion of tumor cells. Overexpression of SUSD2 in MCF-7 revealed upregulation of ER-alpha, 78 kDa glucose-regulated protein (GRP78) downregulation of programmed cell death protein 4 (PDCD4). GRP78 mediates resistance to chemotherapy, whereas loss of PDCD4 is involved in drug resistance and malignant transformation. Database search revealed significantly reduced overall survival in luminal breast cancer for low PDCD4 levels (n=348; p=0.0323). In conclusion, high levels of SUSD2 may confer improved cytoprotection of metastatic breast cancer cells and their CTC travelers to distant organs in the blood.
2025-02-04 | PXD047444 | Pride
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways. Case-control study. Samples were selected according to immunological criteria: those with total loss of HLA antigens and those without alterations in the expression of HLA molecules. In addition, the microsatellite instability genotype of all the samples was also analyzed, resulting in microsatellite stability (MSS) and microsatellite instability (MSI) samples. Therefore, three groups of samples were selected: MSS/HLA+, MSS/HLA-, and MSI. The MSS/HLA+ group was used as the control.
2011-02-28 | E-GEOD-27544 | biostudies-arrayexpress
Project description:Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Recent studies suggest the promising potential of microRNAs (miRNA) in predicting the status of circulating tumor cells (CTC), and their combined analyses could pave the way for significant advancements in assessing the risk of metastatic cancer. Here, we investigate the circulating miRNA signatures associated with CTC status in metastatic CRC (mCRC). The CTC status was assessed using AdnaTest ColonCancer technology, which detects tumor cells using an immunomagnetic approach and characterizes them based on colon-specific surface markers. The miRNA profiles were then analyzed using the Agilent miRNA microarray platform in 8 CTC-positive, 8 CTC-negative, and eight healthy individuals. The functional implications of dysregulated miRNAs and their interactions with target mRNAs, TFs, and lncRNAs were determined through a comprehensive in silico analysis. We identified two groups of downregulated miRNAs associated with CTC status/metastasis and multiple candidate biomarkers in suggested miRNA regulatory networks. Four miRNAs (miR-181c-5p, miR-199a-5p, miR-500b-5p, miR-769-5p) were prioritized as findings were consistent with their tissue expressions in TCGA datasets. Our findings reveal candidate biomarkers with potential for CTC status and mCRC-associated CTC detection, providing insights for new translational medicine applications in mCRC management.
2025-04-16 | GSE285322 | GEO
Project description:Most cancer deaths are caused by metastases, which are the end-results of circulating tumor cells (CTC) that detach from the cancer primary and succeed to survive in distant organs. The aim of the present study was to develop a gene signature of CTC and to assess its prognostic relevance after surgery for pancreatic ductaladenocarcinoma (PDAC). A negative depletion fluorescence activated cell sorting (FACS) procedure was developed and validated with spiking experiments using cancer cell lines in whole human blood samples. This FACS-based method was used to enrich for CTC from the blood of 10 patients who underwent surgery for PDAC. Total RNA was isolated from 4 subgroup samples, i.e. CTC, haematological cells (G), original tumor (T), and non-tumoral pancreatic control tissue (P). After RNA quality control, samples of 6 patients were eligible for further analysis. Whole genome microarray analysis was performed after double linear amplification of RNA. The ‘Ingenuity Pathway Analysis’ software and AmiGO were used for functional data analyses. A CTC gene signature was developed and validated with the nCounter system on expression data of 78 primary PDAC using Cox regression analysis for disease-free (DFS) and overall survival (OS). Using stringent statistical analysis, we finally retained 8,152 genes to compare expression profiles of CTC vs. other subgroups, and found 1,059 genes to be differentially expressed. The pathway with the highest expression ratio in CTC was p38 mitogen-activated protein kinase (p38 MAPK) signaling, known to be involved in cancer cell migration. In the p38 MAPK pathway TGF-β1, cPLA2, and MAX were significantly upregulated. In addition, 9 other genes associated with both p38 MAPK signaling and cell motility were over-expressed in CTC. High co-expression of TGF-1 and our cell motility panel (≥ 4 out of 9 genes for DFS and ≥ 4 out of 9 genes for OS) in primary PDAC was identified as an independent predictor of DFS (p=0.041, HR (95% CI) = 1.885 (1.025 – 3.559)) and OS (p=0.047, HR (95% CI) = 1.366 (1.004 – 1.861)). Pancreatic CTC isolated from blood samples using a FACS-based negative depletion method,express a cell motility gene signature. The expression of this newly defined cell motility gene signature in the primary tumor is able to predict survival of patients who undergo surgical resection for pancreatic cancer. Total RNA was isolated from circulation tumor samples (CTC), haematological cells (G), original tumor (T), and non-tumor pancreatic control tissue (P) of patients with pancreatic ductal adenocarcinoma (PDAC). Gene expression profiles of CTC were compared to G, T, and P. The aim of the current study was to develop a ‘negative depletion strategy’ to isolate CTC without the exclusion of any particular subset of CTC, and to study their gene-expression profiles in order to find novel therapeutic targets and prognostic markers in patients with pancreatic cancer.
2012-12-18 | E-GEOD-18670 | biostudies-arrayexpress
Project description:This study will be looking at whether MK-3475 (an antibody that blocks negative signals to T cells) is effective (anti-tumor activity) and safe in three different patient populations. These include: 1. patients with MSI positive colon cancer, 2. patients with MSI negative colon cancer and 3. patients with other MSI positive cancers.
| 2146558 | ecrin-mdr-crc
Project description:We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7), leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation were used to confirm some microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs. In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways.
2011-02-28 | GSE27544 | GEO
Project description:Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Here, we first use mouse models to demonstrate that breast cancer cells injected intravascularly as clusters are more prone to survive and colonize the lungs than single cells. Primary mammary tumors comprised of tagged cells give rise to oligoclonal CTC-clusters, with 50-fold increased metastatic potential, compared with single CTCs. Using intravital imaging and in vivo flow cytometry, CTC-clusters are visualized in the tumor circulation, and they demonstrate rapid clearance in peripheral vessels. In patients with breast cancer, presence of CTC-clusters is correlated with decreased progression-free survival. RNA sequencing identifies the cell junction protein plakoglobin as most differentially expressed between clusters and single human breast CTCs. Expression of plakoglobin is required for efficient CTC-cluster formation and breast cancer metastasis in mice, while its expression is associated with diminished metastasis-free survival in breast cancer patients. Together, these observations suggest that plakoglobin-enriched primary tumor cells break off into the vasculature as CTC-clusters, with greatly enhanced metastasis propensity. RNA-seq from 29 samples (15 pools of single CTCs and 14 CTC-clusters) isolated from 10 breast cancer patients
2014-07-11 | E-GEOD-51827 | biostudies-arrayexpress
Project description:Transcription profiling by array of human CD4 positive and CD8 positive T cells selected by positive or negative immunomagnetic cell selection
2025-01-24 | E-GEOD-14926 | ExpressionAtlas
Project description:The immune ecosystem, particularly T cells, is central to maintaining effective anti-tumor responses. However, how immune cells in the periphery blood interact with circulating tumor cells (CTCs) - critical mediators of metastatic spread 1-8 – remains largely unexplored. Here, our analysis of the blood specimens from patients with advanced breast cancer (N=1,529) revealed that over 75% of the CTC-positive blood specimens contained heterotypic CTC clusters with CD45+ white blood cells (WBCs). These CTC-WBC clusters correlate with breast cancer subtypes (triple negative and luminal B), racial groups (Black), and unfavorable clinical outcomes. Using flow cytometry and ImageStream, we characterized the diverse WBC composition in these heterotypic clusters, such as overrepresented T cells and underrepresented neutrophils. Most strikingly, a rare subset of CD4 and CD8 double positive T (DPT) cells showed an up to 140-fold enrichment in the CTC clusters (~14.2%) versus its frequency in WBCs (0.1%). DPT cells shared part of profiles with CD4+ T cells and others with CD8+ T cells but exhibited unique features of T cell exhaustion and immune suppression (TIM-3 and PD-1). Single-cell RNA sequencing further identified distinct cell adhesion profiles of DPT cells and CTCs. CRISPR/Cas9-mediated gene depletion pinpointed the integrin VLA4 (β1/α4) in DPT and its ligand VCAM1 in tumor cells as essential mediators of heterotypic CTC clusters. Anti-α4 (VLA4) neutralizing antibodies markedly reduced CTC–DPT cell clustering and blocked metastatic lesion formation in murine models in vivo. These findings uncover a pivotal role for a rare T cell subset in fostering cancer dissemination through heterotypic CTC cluster interactions. It lays a foundation for innovative therapeutic strategies aimed at preventing and targeting metastasis of breast cancer, thus benefiting Black and non-Black patients.
2025-04-18 | GSE294399 | GEO
Project description:Transcriptomic survey of lymph node-positive vs. - negative ductal breast cancer
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