Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression data from healthy, adjacent normal and tumor colon cells

ABSTRACT: Gene expression profiles of paired normal adjacent mucosa and tumor samples from 98 individuals and 50 healthy colon mucosae, were obtained through Affymetrix Human Genome U219 Arrays. This dataset is in the context of the COLONOMICS project and to query additional information you can visit the project website www.colonomics.org. Colon tumor and adjacent paired normal mucosa tissues samples used in this study were selected from a series of cases with a new diagnosis of colorectal adenocarcinoma histologically confirmed. Included cases were from a homogenous series of patients with more than three years of follow up, early stage (II), without neoadjuvant chemotherapy and microsatellite stable colon cancer. Additionally, samples of colon mucosa from 50 healthy donors without colonic lesions were obtained during colonoscopy.

ORGANISM(S): Homo sapiens

SUBMITTER: David Romera

PROVIDER: E-GEOD-44076 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer.

Sanz-Pamplona Rebeca R Berenguer Antoni A Cordero David D Molleví David G DG Crous-Bou Marta M Sole Xavier X Paré-Brunet Laia L Guino Elisabet E Salazar Ramón R Santos Cristina C de Oca Javier J Sanjuan Xavier X Rodriguez-Moranta Francisco F Moreno Victor V

Molecular cancer 20140305

<h4>Background</h4>A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient's gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response.<h4>Methods</h4>A set of 98 paired adj ...[more]

PMID: 24597571

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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.

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.

Dataset Information

Gene expression data from healthy, adjacent normal and tumor colon cells

Publications

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer.

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