MiRNA profiling: Colon Cancer FF tissue from different stages and no previous treatment.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Mateo Paz-Cabezas
PROVIDER: E-MTAB-9288 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Colorectal cancer is the third most common cancer worldwide, with 1.4 million people diagnosed in 2012 according to GLOBOCAN 2012. 95% of the colon cancer cases are that of adenocarcinomas. Removal of high-risk adenomas and tumors at early stage of colorectal cancer (CRC) can prevent its onset/progression into higher grades of cancer. The prognosis of colorectal cancer and the stage of diagnosis are closely correlated. 5-year survival rate is observed among 90% patients when diagnosed early and in less than 10% when the metastases develop. This makes the implementation of screening methods aimed at early detection paramount for reduced incidence and mortality rate. Adenocarcinomas are the cancers originating from the gland forming cells of the colon and rectal lining and are known to be the most common type of colorectal cancer. The current diagnosis options for colorectal cancers are limited to biopsy, stool tests and other laboratory tests, barium enema based imaging and other imaging techniques, colonoscopy and other endoscopic procedures which are time consuming. In this study, we used proteomics approach with an aim to identify protein biomarkers which can aid in early detection of colon adenocarcinomas to be precise. Proteins from tumor tissue of colon adenocarcinoma subjects (n=11) and their matched controls were subjected to 4-plex iTRAQ labelling followed by off-gel fractionation prior to LC-MS/MS run. The mass spectrometry data was analysed independently using two different analysis software - Spectrum Mill (SM) and Trans Proteome Pipeline (TPP). The proteins identified using either SM and/or TPP were subjected to pathway analysis using the Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 and the proteins common between the two analyses were compared with the data from CPTAC portal and Human Protein Atlas. The expression level of the shortlisted panel of proteins was studied in brain cancers as a non-colon adenocarcinoma control group and validated using MRM approach. A list of 285 unique proteins was identified to be significantly dysregulated in colon adenocarcinoma as compared to its matched controls. These proteins were found to be involved in glycolysis, pentose phosphate pathway, biosynthesis of amino acids, protein processing, spliceosome, proteosome, focal adhesion and proteoglycans in cancer. 94 of the 285 proteins were identified by both- SM and TPP. 34 of these 94 proteins were found to be dysregulated with same trend as that in data reported on CPTAC portal and 9 of these 34 proteins were validated using MRM approach. The proteins identified from this study could be validated further to investigate the role of these proteins as potential biomarkers for early detection of colon adenocarcinoma.
2018-03-28 | PXD006509 | Pride
Project description:In this array series, we have characterized the extent and the location of 5hmC loss in colon cancer. We performed genome-wide methylation oxBS and BS analyses with the Illumina Infinium HumanMethylation450 BeadChip platform in 11 normal colon and 11 matched tumor samples plus 2 colon cancer cell lines, and we measured the extent of 5mC and 5hmC in normal versus tumoral conditions.
2023-12-30 | E-MTAB-6183 | biostudies-arrayexpress
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets
2021-09-09 | PXD021318 | Pride
Project description:Background: Multi-omics analyses are profitable for discovering novel biomarkers and drug targets, but such integrated examinations on mitochondria of colorectal cancer (CRC) patients are lacking. Methods: We investigated global structural variants, DNA methylation, chromatin accessibility, proteome, and phosphoproteome on human CRC (n = 6-8). The alterations of mitochondria on these levels and potential upstream regulatory genes were described. Furthermore, combining with the mRNA datasets of 538 CRC and 91 colitis patients from the public databases, we identified independent prognostic factors (IPFs). Findings: Revealed by the proteogenomic analyses in our study, mitochondria altered the most among all organelles in CRC, which were also associated with patient prognosis the most. We found that the mRNA of one nuclear-coding mitochondrial gene (NCMG), HIGD1A, decreased in colitis, two subtypes of adenoma, and six subtypes of CRC, subsequently was identified as a favorable IPF for CRC. Besides, the comprehensive analyses of mitochondria by multi-omics uncovered unique proteogenomic alterations on six survival-related NCMGs. Key transcriptional factors potentially regulating the mitochondria were also unveiled, such as GLIS1, JUN, CREB1, and YAP1. Finally, p38 was highlighted as one possible central kinase involving in the modulation of mitochondrial activity in CRC patients. Interpretation: Our study presents a multilayer and molecular picture of mitochondria of CRC patients, recognizes HIGD1A as a potential prognostic biomarker, and provides new candidate genes as therapeutic targets.
2021-09-09 | PXD021314 | Pride
Project description:Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.
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Project description:In this project, a cohort of early stage NSCLC samples (141) were analyzed by MS-based proteomics in order to identify molecular subtypes at the phenotype level. In total, close to 14 000 proteins were identified and quantified across samples by HiRIEF-LC-MS and TMT based relative quantification. Further, six identified NSCLC proteome subtypes were investigated in relation to cancer driver pathways, immune phenotypes and neoantigen expression based on the generated MS-data.
2021-12-15 | PXD020191 | Pride
Project description:Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health concern worldwide. Vitamin D deficiency is associated with high CRC incidence and mortality, suggesting a protective effect of vitamin D against this neoplasia. Although the antiproliferative and prodifferentiation action of active vitamin D (1alpha,25-dihydroxyvitamin D3, 1,25(OH)2D3) on colon carcinoma cells is well documented, its potential effects on CRC stroma are unknown. Here, we show that high vitamin D receptor (VDR) expression in tumor stromal fibroblasts is associated with better overall and progression-free survival in a large cohort of CRC patients, irrespective of its expression in carcinoma cells. Consistently, 1,25(OH)2D3 inhibits the activation of patient-derived normal and cancer-associated fibroblasts, and their pro-migratory effect on carcinoma cells. Importantly, we show by global transcriptomic analyses that 1,25(OH)2D3 regulates cancer-associated fibroblast gene expression and imposes a gene signature that is associated with longer overall and disease-free survival of CRC patients. Moreover, expression of two genes from the signature, CD82 and S100A4, correlates with stromal VDR expression and clinical outcome in CRC. This study provides the first evidence that vitamin D has protective effects against CRC through the regulation of stromal fibroblasts. Characterization of 1,25(OH)2D3 action on gene expression in primary cultures of colon normal and tumor fibroblasts established from samples from colorectal cancer patients. RNA from seven paired normal and tumor fibroblast primary cultures treated with 1,25(OH)2D3 or vehicle for 48 h were analyzed.
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Project description:The CMS4 sarcoma, kindly provided by A. DeLeo (University of Pittsburgh, Pittsburgh, PA), is a solid tumor of BALB/c (H-2d) origin, which grows aggressively in naive, syngeneic hosts following a s.c. transplant. Although the parental tumor cell line forms few metastatic foci in the lungs following i.v. administration, a highly metastatic subline, termed CMS4-met, was established from lung digests of those mice as described (Ryan MH, Bristol JA, McDuffie E, Abrams SI. Regression of extensive pulmonary metastases in mice by adoptive transfer of antigen-specific CD8(+) CTL reactive against tumor cells expressing a naturally occurring rejection epitope. J Immunol 2001;167:4286-92).<br>In this experiment we compare gene expression kinetics in the CMS4 and CMS4-met cell lines after IFNgamma treatment. Both cells were treated with IFNgamma for 4 and 24 hours respectively. The untreated and treated cells were then used for total RNA isolation, and microarray experiments.
2005-05-08 | E-MEXP-288 | biostudies-arrayexpress
Project description:The CMS4 sarcoma, kindly provided by A. DeLeo (University of Pittsburgh, Pittsburgh, PA), is a solid tumor of BALB/c (H-2d) origin, which grows aggressively in naive, syngeneic hosts following a s.c. transplant. Although the parental tumor cell line forms few metastatic foci in the lungs following i.v. administration, a highly metastatic subline, termed CMS4-met, was established from lung digests of those mice as described (Ryan MH, Bristol JA, McDuffie E, Abrams SI. Regression of extensive pulmonary metastases in mice by adoptive transfer of antigen-specific CD8(+) CTL reactive against tumor cells expressing a naturally occurring rejection epitope. J Immunol 2001;167:4286-92). The CMS4.sel subline was selected from the parental line in vitro following six successive passages in the presence of anti-Fas stimuli as described (Liu K, Abrams SI. Alterations in Fas expression are characteristic of, but not solely responsible for, enhanced metastatic competence. J Immunol 2003;170:5973-80).<br>In this experiment we compare the gene expression patterns of the in vivo-derived CMS4-met cells and the in vitro-derived CMS4.sel cells using CMS4 cells as a reference sample.
2005-05-08 | E-MEXP-286 | biostudies-arrayexpress
Project description:Purpose: Celiac disease (CD) is a risk factor for developing Small Bowel Carcinoma (SBC) with a 14 folds higher risk than that of the general population. As SBCs associated with CD (CD-SBCs) are extremely rare, very few molecular data are currently available about their pathogenesis and information about CD-SBC transcriptomic profiling is completely lacking. Patients and Methods: We generated RNA-seq data on 13 CD-SBCs selected from the largest and well-characterized series of CD-SBCs published so far that was collected by the Small Bowel Cancer Italian Consortium. In all cases we compared the CD-SBC transcriptional signatures with the four consensus molecular subtypes (CMS) of colorectal carcinoma (CRC) applying the ‘CMS classifier’. CpG Island Methylator Phenotype (CIMP+) was evaluated in all cases using methylation-sensitive multiple ligation-dependent probe amplification. Results: RNA-based signatures of CD-SBCs exhibited strong similarities with CRCs. Twelve of 13 CD-SBCs (92%) fell within the two main subtypes exhibiting high immune and inflammatory signatures, i.e. CMS1 and CMS4. CMS1 CD-SBCs (62% of cases) were commonly MSI/CIMP+ tumors and showed increased expression of genes associated with a diffuse TH1 and cytotoxic T immune infiltrate, up-regulation of apoptosis, cell cycle progression and proteasome pathways. CMS4 CD-SBCs (31% of cases) showed prominent TGF-β activation and were characterized by complement-associated inflammation, matrix remodeling, stromal invasion and angiogenesis Conclusions: RNA-based signatures of CD-SBCs strongly recapitulate CMS classification of CRC, give a promising tool to improve our knowledge of this rare entity and provide clinically useful information using the wealth of data available for CRC.
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