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New specific molecular targets for radiochemotherapy in colorectal cancer

ABSTRACT: A promising treatment for patients with advanced colorectal cancer is preoperative radiochemotherapy. The early side effects of this treatment have been considered to be acceptable. The aim of this study was to identify the effects of preoperative radiochemotherapy (PRT) on gene expression in tumour and normal colon rectal tissue form the same patients, before and after PRT. For that purpose, tissue samples from ten patients with operable rectal adenocarcinomas were collected for use in whole genome–microarray based gene expression analysis. A factorial experimental design allowed us to look solely at the radiation effect on tumours. This resulted in 4496 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radiochemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration (TEM). We conclude that radiochemotherapy has a greater effect in tumour tissue gene expression than normal tissue. Not only is the effect on normal tissue limited compared to tumour, but significantly different gene sets are enriched. The profound change of cell adhesion molecule expression in tumour tissue could either increase the risk of metastasis, or decrease the tumours invasive potential. Further characterization of genes involved in cell adhesion and leukocyte TEM may give new insights into the molecular responses to radiochemotherapy in colorectal cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE15781 | GEO | 2009/04/23

SECONDARY ACCESSION(S): PRJNA116855

REPOSITORIES: GEO

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New specific molecular targets for radiochemotherapy in colorectal cancer

Project description:A promising treatment for patients with advanced colorectal cancer is preoperative radiochemotherapy. The early side effects of this treatment have been considered to be acceptable. The aim of this study was to identify the effects of preoperative radiochemotherapy (PRT) on gene expression in tumour and normal colon rectal tissue form the same patients, before and after PRT. For that purpose, tissue samples from ten patients with operable rectal adenocarcinomas were collected for use in whole genomeâmicroarray based gene expression analysis. A factorial experimental design allowed us to look solely at the radiation effect on tumours. This resulted in 4496 differentially expressed genes in tumour tissue with p<0.05. In addition to known markers for radiochemotherapy, a Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in gene sets associated with cell adhesion and leukocyte transendothelial migration (TEM). We conclude that radiochemotherapy has a greater effect in tumour tissue gene expression than normal tissue. Not only is the effect on normal tissue limited compared to tumour, but significantly different gene sets are enriched. The profound change of cell adhesion molecule expression in tumour tissue could either increase the risk of metastasis, or decrease the tumours invasive potential. Further characterization of genes involved in cell adhesion and leukocyte TEM may give new insights into the molecular responses to radiochemotherapy in colorectal cancer. Factorial experimental design

2010-04-09 | E-GEOD-15781 | biostudies-arrayexpress

Genotyping of human chromosomal instability patterns discriminates rectal adenomas from carcinomas

Project description:Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22â24, 13q and 20q, and loss of 17p and 18q12â22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such âmalignant aberrationsâ was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours. Experiment Overall Design: 78 tumor samples and 19 reference normal samples

2008-06-17 | E-GEOD-7946 | biostudies-arrayexpress

SNP array analysis of chromosomal instability patterns discriminates rectal adenomas from carcinomas

Project description:Total mesorectal excision (TME) is the standard treatment for rectal cancer, while transanal endoscopic microsurgery (TEM) is a recently introduced surgical approach for the treatment of rectal adenomas. Incorrect preoperative staging before TEM is a problem. To identify genetic changes that might correlate with tumour stage and could lead to optimized treatment selection we performed a genome-wide chromosomal instability search in a homogeneous, clinical cohort of rectal tumours. 78 rectal tumours during different clinical stages were analysed with 10K single nucleotide polymorphism (SNP) arrays. Logistic regression was performed to build a quantitative model of specific chromosomal aberrations. Overall, most cases (95%) had one or more chromosomal aberrations. We observed a clear correlation between the total number of aberrations and the different tumour stages. Specifically, the chromosomal events: gain of 8q22–24, 13q and 20q, and loss of 17p and 18q12–22, were far more abundant in carcinoma than in adenoma. In adenoma fractions from cases with a carcinoma (infiltrating at least in the submucosa), twice the amount of such ‘malignant aberrations’ was observed, compared to pure adenomas. Furthermore, combined aberrations such as gain of 13q and loss of 18q were only found in adenomatous fractions of carcinomas and not in benign lesions. Based on these five genomic events associated with carcinoma, a clear distinction between adenoma and carcinoma tissue could be made. These data should be validated further in order that they may be used in preoperative staging of rectal tumours. Keywords: SNP array copy number and LOH study

2007-05-30 | GSE7946 | GEO

Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

2013-09-01 | GSE40976 | GEO

Prediction of sensitivity of rectal cancer cells in response to preoperative chemoradiotherapy by DNA microarray analysis of gene expression profiles.

Project description:Samples were prospectively collected during colonoscopic examination from 46 rectal cancer patients before starting preoperative chemoradiotherapy. The expression profiles were determined using Affymetrix Human Genome U133 Plus 2.0 arrays. Comparison between the sample groups allow to identify a set of discriminating genes that can be used for prediction of the response to radiotherapy in rectal cancer. Specimens from 46 rectal cancer patients who approved to receive preoperative chemoradiotherapy were studied. We prospectively collected biopsy specimens during colonoscopic examination from rectal cancer before starting preoperative chemoradiotherapy. Specimens from tumors were snap-frozen in liquid nitrogen and stored at -80 C until use. Paralleled tumor specimens were formalin fixed and paraffin embedded for histologic examination and other specimens were used for RNA extraction. RNA was extracted from tumor tissue using frozen samples. The patients provided written, informed consent to the collection of specimens, and the local Ethics Committee approved the study protocol. All patients received a total dose of 50.4 Gy of radiation, UFT(300-500mg/day) and LV (75mg/day) and underwent standardized curative resection, following an interval of 4 weeks after chemoradiotherapy.

2013-01-29 | E-GEOD-35452 | biostudies-arrayexpress

Identification of a microRNA expression signature for radiochemosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g

Project description:Purpose: Preoperative 5-fluorouracil (5-FU) based radiochemotherapy (RCT) represents the standard treatment for locally advanced rectal cancer. Both, tumor response and progression vary considerably. MicroRNAs represent master regulators of gene expression, and may therefore contribute to this heterogeneity. Results: Thirty-six miRNAs were identified to significantly correlate with sensitivity of CRC cell lines to RCT (q < 0.05). This list included miR320a as most significantly correlated as well as other miRNAs involved in the MAPK-, TGF- and Wnt-pathway. Importantly, transfection of selected miRNAs (let7g, miR-132, miR-224, miR-320a and miR-429) each induced a shift of sensitivity (p<0.00001). Moreover, high expression of miR-224 was associated with a poor prognosis in rectal cancer patients (p=0.043). Experimental design: Genome-wide microRNA (miRNA) profiling was performed from 12 colorectal cancer (CRC) cell lines. To establish an in vitro signature of radiochemosensitivity, these profiles were correlated to the individual sensitivities of each cell line to 5-FU and radiation. The functional relevance of selected miRNAs was validated by transfecting miRNA-mimics into SW480 cells, followed by treatment with 5-FU and radiation. 12 Samples with 3 replicates each.

2013-09-01 | E-GEOD-40976 | biostudies-arrayexpress

Rectal Cancer Cells and Radiation-sensitivity

Project description:Biopsy specimens were collected from rectal cancer before starting preoperative radiotherapy.The expression profiles were determined using Affymetrix Human Genome U95 version 2 arrays.Comparison between the sample groups allow to identify a set of discriminating genes that can be used for characterization of responders and nonresponders to preoperative radiotherapy in rectal cancer. Keywords: repeat

2006-03-29 | GSE3493 | GEO

Transcription profiling of human colorectal cancer biopsies in patients identified as responders/non-responders to preoperative radiotherapy to develop a signature for response to radiotherapy

2007-10-27 | E-GEOD-3493 | biostudies-arrayexpress

Analysis of lncRNAs for the characterization of the response to neoadjuvant chemoradiotherapy

Project description:We investigated the role of lncRNAs to predict the response to preoperative tretament in locally advanced rectal adenocarcinoma

2018-09-01 | GSE116742 | GEO

Transcriptomic effects of medical treatment on gene expression of growth hormone secreting pituitary neruoendocrine tumour biology

Project description:Pituitary neuroendocrine tumours (PitNET) are rare neoplasms of the pituitary gland that can overproduce pituitary hormones or cause headaches and visual impairment due to mass effect. Growth hormone overproducing somatotroph PitNETs cause acromegaly leading to wide range of connective tissue, metabolic and oncologic disorders. The medical treamment of acromegaly is somatostin analogues (SSA) in specific cases combined with dopamine agnoists (DA), but almost half of patients excert SSA resistence and potential causes of this is unknown. The aim of this study was to characterize transcriptomic patterns of somatotroph PitNETs specifically assessing impact of SSA treatment effects. We investigated gene expession on several levels and functional models of GH PitNETs - tumour tissue of patients with and without SSA preoperative treamtment, tumour derived pituisphere model and classically used GH3 cell line treated with SSA.

2022-04-08 | GSE200175 | GEO

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