NDLI: DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

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Cellular Oncology : Volume 39, Issue 5, October 2016

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Cellular Oncology : Volume 39, Issue 2, April 2016

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Cellular Oncology : Volume 34

DNA copy number alterations, gene expression changes and disease-free survival in patients with colorectal cancer: a 10 year follow-up

Content Provider	Springer Nature Link
Author	Bigagli, Elisabetta Filippo, Carlotta Castagnini, Cinzia Toti, Simona Acquadro, Francesco Giudici, Francesco Fazi, Marilena Dolara, Piero Messerini, Luca Tonelli, Francesco Luceri, Cristina
Copyright Year	2016
Abstract	DNA copy number alterations (CNAs) and gene expression changes have amply been encountered in colorectal cancers (CRCs), but the extent at which CNAs affect gene expression, as well as their relevance for tumor development, are still poorly defined. Here we aimed at assessing the clinical relevance of these parameters in a 10 year follow-up study.Tumors and normal adjacent colon mucosa, obtained at primary surgery from 21 CRC patients, were subjected to (i) high-resolution array CGH (a-CGH) for the detection of CNAs and (ii) microarray-based transcriptome profiling for the detection of gene expression (GE) changes. Correlations between these genomic and transcriptomic changes and their associations with clinical and histopathological parameters were assessed with the aim to identify molecular signatures associated with disease-free survival of the CRC patients during a 10 year follow-up.DNA copy number gains were frequently detected in chromosomes 7, 8q, 13, 19, 20q and X, whereas DNA copy number losses were frequently detected in chromosomes 1p, 4, 8p, 15, 17p, 18, 19 and 22q. None of these alterations were observed in all samples. In addition, we found that 2,498 genes were up- and that 1,094 genes were down-regulated in the tumor samples compared to their corresponding normal mucosa (p < 0.01). The expression of 65 genes was found to be significantly associated with prognosis (p < 0.01). Specifically, we found that up-regulation of the IL17RA, IGF2BP2 and ABCC2 genes, and of genes acting in the mTOR and cytokine receptor pathways, were strongly associated with a poor survival. Subsequent integrated analyses revealed that increased expression levels of the MMP9, BMP7, UBE2C, I-CAM, NOTCH3, NOTCH1, PTGES2, HMGB1 and ERBB3 genes were associated with copy number gains, whereas decreased expression levels of the MUC1, E2F2, HRAS and SIRT3 genes were associated with copy number losses. Pathways related to cell cycle progression, eicosanoid metabolism, and TGF-β and apoptosis signaling, were found to be most significantly affected.Our results suggest that CNAs in CRC tumor tissues are associated with concomitant changes in the expression of cancer-related genes. In other genes epigenetic mechanism may be at work. Up-regulation of the IL17RA, IGF2BP2 and ABCC2 genes, and of genes acting in the mTOR and cytokine receptor pathways, appear to be associated with a poor survival. These alterations may, in addition to Dukes' staging, be employed as new prognostic biomarkers for the prediction of clinical outcome in CRC patients.
Starting Page	545
Ending Page	558
Page Count	14
File Format	PDF
ISSN	22113428
Journal	Cellular Oncology
Volume Number	39
Issue Number	6
e-ISSN	22113436
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-10-05
Publisher Institution	International Society for Cellular Oncology
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Colorectal cancer DNA copy number alterations Comparative genomic hybridization (CGH) Gene expression alterations Disease-free survival Cancer Research Biomedicine Pathology Oncology
Content Type	Text
Resource Type	Article
Subject	Cancer Research Molecular Medicine Oncology

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