Association of extracellular matrix gene expression with fraction volumes of particular cell populations in bioptic sample and lymph node metastasis in colorectal cancer.
|Year of publication||2007|
|Type||Article in Proceedings|
|Conference||XI. Pracovní setkání biochemiků a molekulárních biologů. Sborník příspěvků.|
|MU Faculty or unit|
|Field||Oncology and hematology|
|Keywords||extracellular matrix; gene expression; colorectal cancer; cell populations; expression profiling|
|Description||Colorectal cancer (CRC) is one of the most common malignancies. Unfortunately a significant proportion of surgically cured patients in the early stage of the disease develop progression and die from the disease. Lymphatic metastasis strongly determines treatment algorithms in CRC. Currently, postoperative histology results are needed to determine lymph node status. Reliable preoperative information would be useful to advance treatment strategies. Twelve patients (7 with clinical stage II and 5 with clinical stage III with detectable lymph node metastasis) aged 52-76 years, with no neoadjuvant chemotherapy or radiotherapy and histologically confirmed colon adenocarcinoma were included in the study. Relative gene expression levels of 96 genes encoding extracellular matrix and cell adhesion proteins were obtained by commercial low-density cDNA microarrays from 12 primary colon cancer samples. Gene expression data analysis based on the SAM (Significance Analysis of Microarrays) and t-test (alfa = 0,01) methods identified 6 genes with significantly different expression in association with lymph node status. In subsequent cluster analysis this group of genes was able to discriminate lymph node positive from lymph node negative patients. Thrombospondin 1, fibronectin 1, osteonectin and TIMP1 genes were down-regulated and laminin B2 and integrin alfa6 genes were up-regulated in the group of tumors developing lymph node metastasis. All bioptic samples were assessed by pathologist and fraction volumes of particular cell populations were determined (malignant cells, lymphocytes, fibroblasts, granulocytes) in percentual values. Interestingly, remarkable fraction volumes of neutrophil granulocytes and related tumor inflammation rates were identified exclusively in the group of patients with good prognosis (disease free survival longer than 36 month). Extracellular matrix gene expressions were analyzed also in relation to fraction volumes of particular cells populations and significant changes were identified. Our preliminary data confirm pivotal influence of others than malignant cell populations on gene expression profiles and also on tumor phenotype. Analyzing of gene expression data from larger group of CRC patients and validation of results by other more accurate technology (RT-qPCR, imunohistochemistry) will provide preoperative determination of lymph node status of colorectal cancer patients and more individualized therapy in the future. This work was supported by IGA MZ CR NR/9076 - 4|