Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
Oncol Rep. 2011 Oct;26(4):965-70. doi: 10.3892/or.2011.1374. Epub 2011 Jul 1.
Few target molecules have been identified that enable the diagnosis of lung cancer with high sensitivity and specificity, especially in the early clinical stages. Herein, we present the first evidence for mRNA overexpression of SALL4, a transcription factor essential for embryonic development and the self-renewal of embryonic stem cells, in lung cancer. Analysis using cancerous and noncancerous tissues revealed that the sensitivity and specificity of SALL4 mRNA were 85.1 and 92.9%, respectively, estimated using the cutoff value obtained from analyzing the receiver operating characteristic curve. Furthermore, comparison of paired tissues from the same patient revealed elevated SALL4 mRNA levels that were greater than two-fold in 93% of the specimens. SALL4 mRNA was highly expressed even in the early clinical stages and there was no difference in the positivity rate between stage IA and other stages. An siRNA approach to determine the significance of SALL4 expression revealed catastrophic growth inhibition of SBC-1 lung cancer cells that was induced by cell cycle arrest at the G1/early S phase. Therefore, SALL4 mRNA may be a candidate for use as support in the diagnosis of lung cancer, and may also represent a therapeutic target.
目前尚未发现具有高灵敏度和特异性的肺癌诊断靶标分子,尤其是在疾病的早期临床阶段。本文首次报道了转录因子 SALL4 在肺癌中存在 mRNA 过表达,SALL4 对于胚胎发育和胚胎干细胞的自我更新至关重要。通过对癌组织和癌旁正常组织的分析发现,当使用受试者工作特征曲线(receiver operating characteristic curve)分析得到的截断值作为判断标准时,SALL4 mRNA 的灵敏度和特异性分别为 85.1%和 92.9%。此外,对同一患者配对组织的比较显示,93%的标本中 SALL4 mRNA 水平升高超过两倍。SALL4 mRNA 在疾病的早期临床阶段就有高表达,且在 IA 期和其他分期之间的阳性率无差异。通过 siRNA 敲降技术明确了 SALL4 表达的意义,导致 SBC-1 肺癌细胞生长受到抑制,细胞周期阻滞于 G1/早 S 期。因此,SALL4 mRNA 可能成为支持肺癌诊断的候选分子,也可能成为治疗靶点。