Dataset Information


Chronic hypoxia in patients with colon carcinoma

ABSTRACT: In Western countries, colorectal cancer (CRC) is the third most common cancer in both men and women and the second leading cause of cancer-related deaths (approximately 500,000 deaths annually). For CRC, the tumor stage is the main prognostic factor for survival or relapse after surgery. Current staging is based on the AJCC classification which takes into account tumor size/depth, lymph node involvement and distant metastases. Surgical intervention can cure a significant portion of the patients, especially those that are presented in stages I, II or III (around 75% of patients). Patients in stage II undergo surgery only, whereas stage III patients receive adjuvant chemotherapy. However, a major fraction of these patients either have no need for adjuvant treatment (40% stage III) or would benefit when they were given adjuvant therapy in stage II. Therefore, in the current practice, the majority of patients receive not the optimal treatment. An accurate and reliable method that identifies patients with low and high risk for recurrence could improve the selection for adjuvant therapies in these groups, reducing over- or under-treatment. Molecular profiling of mRNA expression by microarray is an approach to identify relevant genes and gene signatures and has been used already for different types of cancer, like breast and HCC. Most studies, however, resulted in their own classification with a specific separation into groups. Most of these microarray studies show remarkably little overlap and it is difficult to find a clear correlation between the molecular classes and prognosis. The results of the studies seem to be center-dependent because of the different microarray techniques used, the small heterogeneous cohorts that are studied and the different clinical parameters used for the evaluation. Recently, we used a mechanism-driven approach to find a correlation between gene expression in HCC and prognosis in which we tried to overcome most shortcomings (van Malenstein et al. CCR 2010). In this study, we want to apply the approach which we used for HCC now in CRC with the aim to improve the prognosis prediction for patients in AJCC stage II and III. We determined the gene expression by microarray in the colon cancer cell line Caco2 and identified the genes that are differentially expressed under hypoxia (72 hours, 2% O2). Using a bioinformatic approach, we used 5 sets of expression data with corresponding clinical information (training: 3 sets, 234 patients and validation: 2 sets, 322 patients). This resulted in a unique 21 gene set with good performance in retrospective analysis. A second improvement we wanted to achieve is the development of a method that can be applied on FFPE material, which would expand the use of the technique to samples outside the university or research setting. We used the nCounter technique that uses hybridization of labeled probes and quantification without an amplification step. We tested our 21 genes on a cohort of 384 well-characterized patients that were collected between 2004 and 2006 at the University Hospitals of Leuven. We compared cells under hypoxia 2% O2 versus 20% O2 conditions. This was done for two cell lines (Caco2 human colorectal adenocarcinoma cell line and HPAC pancreas adenocarcinoma cell line). Each sample has a biological replicate. Samples are hybridized in dye-swap, resulting in 4 hybridizations per cell line.

ORGANISM(S): Homo sapiens  

SUBMITTER: H van Malenstein   B De Moor  X Sagaert  D Hompes  E Van Cutsem  D Popovic  L Libbrecht  Wouter Van Delm  A D'Hoore  J van Pelt  A Daemen  C Verslype 

PROVIDER: E-GEOD-31079 | ArrayExpress | 2014-05-22



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Hypoxia-driven gene expression is an independent prognostic factor in stage II and III colon cancer patients.

Dekervel Jeroen J   Hompes Daphne D   van Malenstein Hannah H   Popovic Dusan D   Sagaert Xavier X   De Moor Bart B   Van Cutsem Eric E   D'Hoore André A   Verslype Chris C   van Pelt Jos J  

Clinical cancer research : an official journal of the American Association for Cancer Research 20140131 8

Hypoxia is considered a major microenvironmental factor influencing cancer behavior. Our aim was to develop a hypoxia-based gene score that could identify high and low risk within stage II and III colon cancer patients.Differential gene expression of CaCo-2 colon cancer cells cultured in chronic hypoxia versus normoxia was tested for correlation with prognostic variables in published microarray datasets. These datasets were further used to downsize and optimize a gene score, which was subsequent  ...[more]

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