Publication details

Molecular characterization of primary colorectal cancers with progressive metastatic phenotype by oligonucleotide microarrays


SLABÝ Ondřej GARAJOVÁ Ingrid SVOBODA Marek SVOBODA Miroslav VYZULA Rostislav

Year of publication 2006
Type Article in Proceedings
Conference sborník XX. BIOCHEMICKÝ ZJAZD
MU Faculty or unit

Faculty of Medicine

Field Oncology and hematology
Keywords colorectal cancer; DNA microarray technology; gene expression; pathogenesis; prognosis; prediction
Description PURPOSE: Colorectal cancer (CRC) is one of the most common malignancies. Unfortunately a significant proportion of surgically cured patiens in the early stage of the disease develop progression and die from the disease. This study aimed to find individual up/down-regulated genes associated with progression and metastatic potential of colorectal cancers using low-density oligonucleotide microarrays. Molecular characterization of patients at high risk of cancer progression may assist to oncologists in treatment decision by selecting those patients who will need adjuvant chemotherapy. PATIENTS AND METHODS: Patients who underwent surgical resection were divided into different prognostic groups by disease-free survival (DFS>36 month – good prognosis; DFS<36 month – bad prognosis). Total RNA was extracted from each frozen tumor specimen and gene expression profiles were obtained using a human oligonucleotide microrray (SuperArray) spotted with 128 genes known to be involved in metastasis. Genes with expression levels showing at least a 2-fold difference were identified as differentially expressed. RESULTS: Characteristic gene expression profiles were obtained from tumor specimens of prognostically different patients with CRC. Expression analysis identified 21 differentially expressed genes (19 up-regulated, 2 down-regulated) in primary tumors of patients who had progressive disease (DFS<36). The functional categories of up-regulated genes belonged to cell cycle (MYC, HRAS, TP53), adhesion molecules (cadherins CDH8, CDH11, CDH19; molecule CD44; catenins CTNNA1, CTNNB1; chemokine CXCR4), matrix metalloproteinases (MMP7, MMP9, MMP10, MMP11, MMP13) and prometastatic factors such as growth factor IGF1, metastasis associated protein MTA1, transcription factor ETV4 (e.g. COX-2 and MMP-7 promoters activation) and scaffolding protein CAV1. The lower expression levels showed genes encoding negative cell proliferation regulator NME1 and plasminogen activator PLAUR. All of these expression differences are consistent with previous reports and molecular and cellular aspects of cancer progression and metastasis. CONCLUSIONS: Our preliminary data suggest that oligonucleotide microarray technology should contribute to a better understanding of the progression of colorectal cancers, and facilitate prediction of their metastatic potential. Analyzing of gene expression data from larger group of CRC patients will enable us to identify distinct prognostic subsets of patients based on molecular characteristics in the near future. This work was supported by IGA MZ ČR NR/9076 - 4

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