软骨粘连蛋白是一种新型的肺癌诊断生物标志物和治疗靶点。
Chondrolectin is a novel diagnostic biomarker and a therapeutic target for lung cancer.
机构信息
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
出版信息
Clin Cancer Res. 2011 Dec 15;17(24):7712-22. doi: 10.1158/1078-0432.CCR-11-0619. Epub 2011 Oct 20.
PURPOSE
This study aims to identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies for lung cancer.
EXPERIMENTAL DESIGN
We screened for genes that were highly transactivated in a large proportion of 120 lung cancers by means of a cDNA microarray representing 27,648 genes and found chondrolectin (CHODL) as a candidate. Tumor tissue microarray was applied to examine the expression of CHODL protein and its clinicopathologic significance in archival non-small cell lung cancer (NSCLC) tissues from 295 patients. A role of CHODL in cancer cell growth and/or survival was examined by siRNA experiments. Cellular invasive effect of CHODL on mammalian cells was examined by Matrigel assays.
RESULTS
Immunohistochemical staining revealed that strong positivity of CHODL protein was associated with shorter survival of patients with NSCLC (P = 0.0006), and multivariate analysis confirmed it to be an independent prognostic factor. Treatment of lung cancer cells with siRNAs against CHODL suppressed growth of the cancer cells. Furthermore, induction of exogenous expression of CHODL conferred growth and invasive activity of mammalian cells.
CONCLUSIONS
CHODL is likely to be a prognostic biomarker in the clinic and targeting CHODL might be a strategy for the development of anticancer drugs.
目的
本研究旨在鉴定可能作为诊断/预后生物标志物以及作为开发肺癌新分子疗法的靶点的分子。
实验设计
我们通过代表 27648 个基因的 cDNA 微阵列筛选了大量(120 个)肺癌中高度转录激活的基因,发现软骨凝集素(CHODL)为候选基因。应用肿瘤组织微阵列检测了 295 例非小细胞肺癌(NSCLC)组织中 CHODL 蛋白的表达及其临床病理意义。通过 siRNA 实验研究了 CHODL 在癌细胞生长和/或存活中的作用。通过 Matrigel 测定研究了 CHODL 对哺乳动物细胞的侵袭作用。
结果
免疫组织化学染色显示,CHODL 蛋白强阳性与 NSCLC 患者的生存时间较短相关(P=0.0006),多变量分析证实其为独立的预后因素。用针对 CHODL 的 siRNA 处理肺癌细胞可抑制癌细胞的生长。此外,诱导外源性表达 CHODL 赋予了哺乳动物细胞的生长和侵袭活性。
结论
CHODL 可能是临床中的预后生物标志物,靶向 CHODL 可能是开发抗癌药物的策略。