School of Medicine, The University of Queensland, QLD, Australia.
Genes Chromosomes Cancer. 2010 Aug;49(8):688-98. doi: 10.1002/gcc.20779.
Asbestos-related lung cancer accounts for 4-12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos-related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC-AC: asbestos-related lung cancer-adenocarcinoma) with 24 patients with no asbestos bodies (NARLC-AC: non-asbestos related lung cancer-adenocarcinoma). Genes differentially expressed between ARLC-AC and NARLC-AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT-PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons.
与石棉相关的肺癌占全球所有肺癌的 4-12%。由于石棉和烟草诱发的肺癌的致癌机制不同，因此这两种物质引起的肿瘤在基因上可能存在差异。为了确定与石棉相关的肺癌肿瘤发生相关的基因表达生物标志物，我们对 36 名患有原发性肺腺癌的患者的肿瘤进行了基因表达数组分析，将 12 名具有与城市居住相关的石棉体计数水平以上的患者（ARLC-AC：石棉相关肺癌-腺癌）与 24 名无石棉体的患者（NARLC-AC：非石棉相关肺癌-腺癌）进行了比较。根据 fold change 和 P 值确定了 ARLC-AC 和 NARLC-AC 之间差异表达的基因，并使用基因本体论对其进行了优先级排序。候选基因包括 ZNRF3、ADAM28、PPP1CA、IRF6、RAB3D 和 PRDX1。这些六个基因的表达在训练集中通过 qRT-PCR 进行了技术和生物学复制，并在三个独立的测试集中进行了生物学验证。ADAM28 编码一种具有整合素相互作用的解整合素和金属蛋白酶结构域蛋白，在所有四个数据集的 ARLC 中均一致上调。目前正在设计进一步的研究来探讨该基因在石棉肺肿瘤发生中的可能作用、作为石棉相关肺癌因果归因标志物的潜在用途以及作为暴露于石棉的人群中发生的肺癌的治疗靶点的潜在用途。
