OncoCyte Corporation, Alameda, CA 94502, USA.
Future Oncol. 2012 Aug;8(8):1031-40. doi: 10.2217/fon.12.79.
The identification of molecular markers that are upregulated in multiple tumor types could lead to novel diagnostic and therapeutic strategies. The authors screened a panel of RNAs prepared from diverse tumors and tumor cell lines, and compared them with normal tissues and cultured somatic cell types, in order to identify candidate genes expressed in a broad spectrum of tumor types.
MATERIALS & METHODS: Gene expression microarray analysis was carried out on 128 individual tumor samples representing over 20 tumor types, 85 samples representing 31 diverse normal tissue types, 68 tumor cell lines and 97 diverse normal primary cell cultures. Genes were ranked for elevated expression across a large number and variety of tumors relative to normal tissues.
RESULTS & CONCLUSION: COL10A1 was identified as a gene with restricted expression in most normal tissues and elevated expression in many diverse tumor types. By contrast, COL10A1 expression was undetectable in the 68 tumor cell lines surveyed in this study. Immunofluorescence studies localized collagen, type X, α-1 (collagen X) staining to tumor vasculature in breast tumors, whereas the vasculature of normal breast tissue was either collagen X-negative or had markedly lower levels. The tumor microenvironment-specific expression of collagen X, together with its localization in the vasculature, may facilitate its use as a novel target for the diagnosis and treatment of diverse solid tumor types.
鉴定在多种肿瘤类型中上调的分子标志物可能会带来新的诊断和治疗策略。作者筛选了一组来自不同肿瘤和肿瘤细胞系的 RNA 进行分析,并将其与正常组织和培养的体细胞类型进行比较,以鉴定在广泛的肿瘤类型中表达的候选基因。
对 128 个个体肿瘤样本(代表 20 多种肿瘤类型)、85 个代表 31 种不同正常组织类型的样本、68 个肿瘤细胞系和 97 个不同的正常原代细胞培养物进行了基因表达微阵列分析。根据基因在大量和多种肿瘤中的相对正常组织的高表达情况对其进行排序。
COL10A1 被鉴定为一种在大多数正常组织中表达受限但在许多不同肿瘤类型中表达上调的基因。相比之下,在本研究中调查的 68 个肿瘤细胞系中未检测到 COL10A1 的表达。免疫荧光研究将胶原蛋白 X 的染色定位于乳腺肿瘤的肿瘤血管中,而正常乳腺组织的血管要么缺乏胶原蛋白 X,要么水平明显较低。胶原蛋白 X 在肿瘤微环境中的特异性表达及其在血管中的定位,可能使其成为诊断和治疗多种实体肿瘤类型的新靶点。