Carrer Alessandro, Zacchigna Serena, Balani Alessandro, Pistan Valentina, Adami Adelino, Porcelli Fabio, Scaramucci Monica, Roseano Mauro, Turoldo Angelo, Prati Maria Cristina, Dell'Omodarme Matteo, de Manzini Nicolo', Giacca Mauro
Molecular Medicine Laboratory, International Centre for Genetic Engineering and Biotechnology, Area Science Park, Trieste, Italy.
Eur J Cancer. 2008 Aug;44(12):1761-9. doi: 10.1016/j.ejca.2008.05.014. Epub 2008 Jul 23.
The development of new blood and lymphatic vessels is a crucial event for cancer growth, metastatic spread and relapse after therapy. In this work, the expression levels of chemokines, angiogenic and angiostatic factors and their receptors were determined in paired mucosal and tumour samples of patients with colorectal carcinoma and correlated with clinical and histological parameters by advanced multivariate analyses. The most important predictors to discriminate between tumour and paired normal mucosa turned out to be the levels of expression of plexin-A1 and stromal cell-derived factor 1 (SDF-1), the former overexpressed and the latter downregulated in tumours. The levels of osteopontin and Tie-2 transcripts discriminated between the presence and absence of lymph node infiltration, the former overexpressed in the presence of infiltration whilst the latter providing a protective role. These results add support to the notion that the expression levels of selected genes involved in new blood and lymphatic vessel formation represent trustable biomarkers of tumour development and invasion and contribute to the identification of novel molecular classifiers for colorectal carcinoma.
新血管和淋巴管的形成是癌症生长、转移扩散及治疗后复发的关键事件。在本研究中,我们测定了结直肠癌患者配对的黏膜和肿瘤样本中趋化因子、血管生成和血管生成抑制因子及其受体的表达水平,并通过先进的多变量分析将其与临床和组织学参数相关联。鉴别肿瘤和配对正常黏膜的最重要预测指标是丛蛋白-A1和基质细胞衍生因子1(SDF-1)的表达水平,前者在肿瘤中过度表达,后者在肿瘤中下调。骨桥蛋白和Tie-2转录本水平可鉴别有无淋巴结浸润,前者在有浸润时过度表达,而后者起到保护作用。这些结果支持了这样一种观点,即参与新血管和淋巴管形成的特定基因的表达水平是肿瘤发展和侵袭的可靠生物标志物,并有助于鉴定结直肠癌的新型分子分类器。