Inserm, UMR 892, Nantes F-44007, France.
BMC Med Genomics. 2009 Nov 10;2:65. doi: 10.1186/1755-8794-2-65.
Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers.
To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors.
Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type.
Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.
鼻窦腺癌是一种罕见的肿瘤,发生在接触木尘后的筛窦。虽然这些肿瘤的病因已经明确,但对其分子基础知之甚少,也没有用于高危工人早期检测的诊断工具。
为了确定参与这种疾病的基因,我们使用专门针对癌症的微阵列对 9 个鼻窦腺癌和非肿瘤鼻窦组织的匹配样本进行了基因表达谱分析。微阵列结果通过另外两组肿瘤的定量 RT-PCR 和免疫组织化学进行了验证。
在具有显著差异表达的基因中,我们选择 LGALS4、ACS5、CLU、SRI 和 CCT5 进行进一步探索。LGALS4、ACS5、SRI、CCT5 的过表达和 CLU 的下调通过定量 RT-PCR 得到了证实。对 LGALS4(半乳糖凝集素 4)、ACS5(酰基辅酶 A 合成酶)和 CLU(聚集素)蛋白进行了免疫组织化学检测:LGALS4 高度上调,特别是在分化程度最高的肿瘤中,而 CLU 在所有肿瘤中均丢失。ACS5 的表达更为异质,与肿瘤类型无相关性。
在我们对鼻窦腺癌的微阵列研究中,我们鉴定了两种蛋白质,LGALS4 和 CLU,它们在肿瘤与正常组织之间的表达存在显著差异。在包括癌前阶段和低度肿瘤在内的新的组织样本中进行进一步评估,以评估将它们用作诊断标志物的可能性。