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A Gene Expression Signature for Chemoradiosensitivity of Colorectal Cancer Cells

ABSTRACT: In this study, we use cancer cell lines to investigate the molecular differences between resistant and responsive colorectal cancer cells. Since the treatment of patients with locally advanced rectal cancers involves chemoradiotherapy (CT/RT), we specifically implemented an in vitro protocol that mimics this clinical setting. We anticipate that this analysis will unveil relevant pathways underlying the resistance of rectal cancers to CT/RT, and enable the identification of novel therapeutic target genes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE20298 | GEO | 2011/02/10

SECONDARY ACCESSION(S): PRJNA125331

REPOSITORIES: GEO

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A Gene Expression Signature for Chemoradiosensitivity of Colorectal Cancer Cells

Project description:In this study, we use cancer cell lines to investigate the molecular differences between resistant and responsive colorectal cancer cells. Since the treatment of patients with locally advanced rectal cancers involves chemoradiotherapy (CT/RT), we specifically implemented an in vitro protocol that mimics this clinical setting. We anticipate that this analysis will unveil relevant pathways underlying the resistance of rectal cancers to CT/RT, and enable the identification of novel therapeutic target genes. 12 colorectal cancer (CRC) cell lines were obtained from the ATCC, and cultured in the respective tissue culture medium as recommended by the ATCC: Caco-2, HT-29, LS411N, LS513, LS1034, SW403, SW480, SW620, SW837, SW1116, SW1463, and WiDr. For each cell line, RNA was independently isolated at three different passages, and hybridized to a gene expression array. Accordingly, there are three biological triplicates per cell line. Additionally, SW480 (triplicate), SW837 (triplicate), and Caco-2 (duplicate) were cultured in RPMI.

2011-02-10 | E-GEOD-20298 | biostudies-arrayexpress

Hypermethylation and downregulation of UTP6 are associated with stemness properties, chemoradiotherapy resistance and prognosis in rectal cancer: A co-expression network analysis

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RNA-seq of human colorectal cancer cell line COLO320DM treated with the secretome of irradiated or control cancer-associated fibroblasts for 6 or 48 hours

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Project description:The treatment strategy of rectal cancer has substantially changed in recent decades. Historically postoperative chemoradiotherapy (CRT) was considered to be the first-line therapy for stage II and III rectal cancers. However, the preoperative CRT is now considered to be the optimal therapy regimen for locally advanced rectal ancer due to its improved local control, reduced toxicity, and increased rate of sphincter preservation. Our study established a clinically practical multi-class prediction model by adopting a novel strategy that applies two separate prediction models (MI and TO predictor) sequentially to a patient to predict the response. For promising clinical practice, we validated our model in a published dataset, which is completely independent dataset from ours. This study suggests a clinically plausible prediction model that correctly infers the preoperative CRT response of patients with high accuracy based on 163 gene signatures we identified. Total RNAs were isolated from primary rectal tumor tissues of 69 patients who underwent chemoradiation therapy (CRT). These patients are classified into four different CRT responses: minimal response (MI), moderate response (MO), near total response (NT) and total response (TO). All the RNAs were subjected to microarray analysis using Affymetrix GenChip arrays.

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Predicting multi-class responses to preoperative chemoradiotherapy in rectal patients

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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.

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Rectal cancer sub-clones respond differentially to neoadjuvant therapy

Project description:Unique sub-clones within rectal tumors may harbor mutations which contribute to inter-patient variation in response to neoadjuvant chemoradiotherapy (nCRT). Analysis of the influence of nCRT on the extent and nature of intra-tumoral genetic heterogeneity in rectal cancer may provide insights into mechanisms of resistance. Ten locally advanced rectal cancer patients underwent pre-treatment biopsies. At the time of surgery, tissue from the treated tumor was obtained and analyzed. Pre- and post-treatment specimens were subjected to whole exome and confirmatory deep sequencing for somatic mutations. Copy number variation was assessed using OncoScan SNP arrays. In total, data from 32 pre/post-treatment samples are provided. The provided data include the pre/post tumor samples and the Affymetrix OncoScan SNP arrays.

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