Department of Thoracic Surgery, Cancer Hospital and Institute, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China.
Clin Cancer Res. 2011 Nov 1;17(21):6802-11. doi: 10.1158/1078-0432.CCR-11-0419. Epub 2011 Sep 2.
Recent studies have suggested that microRNA biomarkers could be useful for stratifying lung cancer subtypes, but microRNA signatures varied between different populations. Squamous cell carcinoma (SCC) is one major subtype of lung cancer that urgently needs biomarkers to aid patient management. Here, we undertook the first comprehensive investigation on microRNA in Chinese SCC patients.
MicroRNA expression was measured in cancerous and noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I-III), who had not been treated with chemotherapy or radiotherapy prior to surgery. The molecular targets of proposed microRNA were further examined.
We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR-486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34 patients) and 96.2% in a test cohort (26 patients). We also showed that high expression of hsa-miR-31 was associated with poor survival in these 60 SCC patients by Kaplan-Meier analysis (P = 0.007), by univariate Cox analysis (P = 0.011), and by multivariate Cox analysis (P = 0.011). This association was independently validated in a separate cohort of 88 SCC patients (P = 0.008, 0.011, and 0.003 in Kaplan-Meier analysis, univariate Cox analysis, and multivariate Cox analysis, respectively). We then determined that the tumor suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.
Our results identified a new diagnostic microRNA classifier for SCC among Chinese patients and a new prognostic biomarker, hsa-miR-31.
最近的研究表明，miRNA 生物标志物可用于对肺癌亚型进行分层，但 miRNA 特征在不同人群之间存在差异。鳞状细胞癌 (SCC) 是一种主要的肺癌亚型，迫切需要生物标志物来辅助患者管理。在这里，我们对中国 SCC 患者中的 miRNA 进行了首次全面研究。
我们严格从中国 SCC 患者（I-III 期）的癌组织和非癌组织中测量 miRNA 表达，这些患者在手术前未接受化疗或放疗。进一步检查了提出的 miRNA 的分子靶标。
我们确定了一个由 5 个 miRNA 组成的分类器（hsa-miR-210、hsa-miR-182、hsa-miR-486-5p、hsa-miR-30a 和 hsa-miR-140-3p），可将 SCC 与正常肺组织区分开来。该分类器在训练队列（34 例患者）中的准确率为 94.1%，在测试队列（26 例患者）中的准确率为 96.2%。我们还通过 Kaplan-Meier 分析（P = 0.007）、单变量 Cox 分析（P = 0.011）和多变量 Cox 分析（P = 0.011）显示，这些 60 例 SCC 患者中 hsa-miR-31 的高表达与生存不良相关。该关联在另外 88 例 SCC 患者的队列中得到了独立验证（在 Kaplan-Meier 分析、单变量 Cox 分析和多变量 Cox 分析中，P = 0.008、0.011 和 0.003）。然后，我们确定肿瘤抑制因子 DICER1 是 hsa-miR-31 的靶标。在人肺癌细胞系中，hsa-miR-31 的表达抑制了 DICER1 的活性，但不抑制 PPP2R2A 或 LATS2。
我们的研究结果确定了一种新的用于中国 SCC 患者的诊断性 miRNA 分类器，以及一种新的预后生物标志物 hsa-miR-31。
