打开APP

Oncogene:科学家发现吸烟者患肺癌的生物标记物

  1. 吸烟者
  2. 肺癌

来源:生物谷 2013-09-22 16:03

2013年9月22日讯 /生物谷BIOON/--科学家发现两个蛋白能够很好的作为预测吸烟者患肺癌的生物标记物。这两个蛋白分别是ASCL1和RET。RET是已知的原癌基因,而ASCL1能够增加RET的表达。该发现发表在近期的Oncogene杂志上。

2013年9月22日讯 /生物谷BIOON/--科学家发现两个蛋白能够很好的作为预测吸烟者患肺癌的生物标记物。这两个蛋白分别是ASCL1和RET。RET是已知的原癌基因,而ASCL1能够增加RET的表达。该发现发表在近期的Oncogene杂志上。

该文章的通讯作者是Mayo Clinic的研究员George Vasmatzis博士,Vasmatzis博士称,该发现非常振奋人心,因为我们相信发现的两个蛋白有望能够作为治疗的靶点。ASCL1和RET是恶性腺瘤的生物标记物。而该病是吸烟者中最常见的癌症。

之前研究发现ASCL1能够控制神经内分泌细胞的发育,并认为与甲状腺癌和小细胞肺癌发展相关,但是不与吸烟相关肺癌相关。而本研究发现病人ASCL1阳性癌细胞引起高水平的RET原癌基因表达,导致该类型病人的存活时间比低水平RET表达病人短。

科学家在肺癌细胞系中阻断ASCL1蛋白的表达,发现RET表达也会变低,同时癌细胞生长减缓。科学家相信基于该发现将有望开发出新的治疗药物。(生物谷Bioon.com)

ASCL1 and RET expression defines a clinically relevant subgroup of lung adenocarcinoma characterized by neuroendocrine differentiation

F Kosari, C M Ida, M-C Aubry, L Yang, I V Kovtun, J L S Klein, Y Li, S Erdogan, S C Tomaszek, S J Murphy, L C Bolette, C P Kolbert, P Yang, D A Wigle, G Vasmatzis.

ASCL1 is an important regulatory transcription factor in pulmonary neuroendocrine (NE) cell development, but its value as a biomarker of NE differentiation in lung adenocarcinoma (AD) and as a potential prognostic biomarker remains unclear. We examined ASCL1 expression in lung cancer samples of varied histologic subtype, clinical outcome and smoking status and compared with expression of traditional NE markers. ASCL1 mRNA expression was found almost exclusively in smokers with AD, in contrast to non-smokers and other lung cancer subtypes. ASCL1 protein expression by immunohistochemical (IHC) analysis correlated best with synaptophysin compared with chromogranin and CD56/NCAM. Analysis of a compendium of 367 microarray-based gene expression profiles in stage I lung adenocarcinomas identified significantly higher expression levels of the RET oncogene in ASCL1-positive tumors (ASCL1+) compared with ASCL1? tumors (q-value <10?9). High levels of RET expression in ASCL1+ but not in ASCL1- tumors was associated with significantly shorter overall survival (OS) in stage 1 (P=0.007) and in all AD (P=0.037). RET protein expression by IHC had an association with OS in the context of ASCL1 expression. In silico gene set analysis and in vitro experiments by ASCL1 shRNA in AD cells with high endogenous expression of ASCL1 and RET implicated ASCL1 as a potential upstream regulator of the RET oncogene. Also, silencing ASCL1 in AD cells markedly reduced cell growth and motility. These results suggest that ASCL1 and RET expression defines a clinically relevant subgroup of ~10% of AD characterized by NE differentiation.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->