Department of Physiology and Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Carcinogenesis. 2012 May;33(5):1046-54. doi: 10.1093/carcin/bgs100. Epub 2012 Feb 13.
About 30% stage I non-small cell lung cancer (NSCLC) patients undergoing resection will recur. Robust prognostic markers are required to better manage therapy options. MicroRNAs (miRNAs) are a class of small non-coding RNAs of 19-25 nt and play important roles in gene regulation in human cancers. The purpose of this study is to identify miRNA expression profiles that would better predict prognosis of stage I NSCLC. MiRNAs extracted from 527 stage I NSCLC patients were profiled on the human miRNA expression profiling v2 panel (Illumina). The expression profiles were analyzed for their association with cancer subtypes, lung cancer brain metastasis and recurrence/relapse free survival (RFS). MiRNA expression patterns between lung adenocarcinoma and squamous cell carcinoma differed significantly with 171 miRNAs, including Let-7 family members and miR-205. Ten miRNAs associated with brain metastasis were identified including miR-145*, which inhibit cell invasion and metastasis. Two miRNA signatures that are highly predictive of RFS were identified. The first contained 34 miRNAs derived from 357 stage I NSCLC patients independent of cancer subtype, whereas the second containing 27 miRNAs was adenocarcinoma specific. Both signatures were validated using formalin-fixed paraffin embedded and/or fresh frozen tissues in independent data set with 170 stage I patients. Our findings have important prognostic or therapeutic implications for the management of stage I lung cancer patients. The identified miRNAs hold great potential as targets for histology-specific treatment or prevention and treatment of recurrent disease.
约 30%接受手术切除的 I 期非小细胞肺癌 (NSCLC) 患者会复发。需要强有力的预后标志物来更好地管理治疗选择。微小 RNA (miRNA) 是一类 19-25 个核苷酸的小非编码 RNA，在人类癌症的基因调控中发挥重要作用。本研究的目的是确定 miRNA 表达谱，以更好地预测 I 期 NSCLC 的预后。从 527 例 I 期 NSCLC 患者中提取的 miRNAs 在人类 miRNA 表达谱 v2 面板 (Illumina) 上进行了分析。对表达谱进行了分析，以确定其与癌症亚型、肺癌脑转移和无复发生存 (RFS) 的关系。肺腺癌和鳞状细胞癌之间的 miRNA 表达模式差异显著，有 171 个 miRNA，包括 Let-7 家族成员和 miR-205。鉴定出与脑转移相关的 10 个 miRNA，包括抑制细胞侵袭和转移的 miR-145*。鉴定出两个高度预测 RFS 的 miRNA 特征。第一个包含 34 个 miRNA，源自 357 例独立于癌症亚型的 I 期 NSCLC 患者，而第二个包含 27 个 miRNA 是腺癌特异性的。在包含 170 例 I 期患者的独立数据集的福尔马林固定石蜡包埋和/或新鲜冷冻组织中，对两个特征进行了验证。我们的发现对 I 期肺癌患者的管理具有重要的预后或治疗意义。鉴定出的 miRNA 作为组织学特异性治疗或预防和治疗复发性疾病的靶点具有很大的潜力。
