Slaby O, Sobkova K, Svoboda M, Garajova I, Fabian P, Hrstka R, Nenutil R, Sachlova M, Kocakova I, Michalek J, Smerdova T, Knoflickova D, Vyzula R
Masaryk Memorial Cancer Institute, Department of Oncological and Experimental Pathology, 656 53 Brno, Czech Republic.
Oncol Rep. 2009 May;21(5):1235-41. doi: 10.3892/or_00000346.
Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management of the disease. We analysed gene expression profiles of CRC patiens by low-density cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC.
结直肠癌(CRC)是世界上最常见的恶性疾病之一。癌症转移至淋巴结是该疾病进展和治疗管理的关键因素。我们通过低密度癌症聚焦寡核苷酸微阵列分析了结直肠癌患者的基因表达谱,以识别疾病程度的新预测标志物,并更好地理解结直肠癌的进展。通过低密度寡核苷酸微阵列从20个肿瘤样本中获得了已知参与癌症生物学的440个基因的相对表达水平。基因表达数据的统计分析确定了3个基因(HSP110、HYOU1和TCTP)在发生淋巴结转移患者的原发性肿瘤中显著上调。我们首次表明,HSP110和HYOU1表达上调与结直肠癌的淋巴结受累有关。我们通过实时PCR在30名所有临床阶段的独立患者组中验证了HSP110表达的差异。我们发现与相邻非肿瘤组织相比,结直肠癌肿瘤中HSP110表达显著上调(p<0.0003)。我们观察到转移性疾病和局限性疾病之间HSP110基因表达存在显著差异(p=0.031),且HSP110基因表达与结直肠癌患者的总生存率呈负相关趋势。我们认为HSP110基因是结直肠癌中有前景的分子预测指标。