MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer
MicroRNA profiling and prediction of recurrence/relapse-free survival in stage I lung cancer
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DOI：
10.1093/carcin/bgs100
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发表时间：
2012-05-01
期刊：
影响因子：
4.7
通讯作者：
You, Ming
中科院分区：
文献类型：
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作者：
Lu, Yan;Govindan, Ramaswamy;You, Ming
约30%接受切除手术的I期非小细胞肺癌（NSCLC）患者会复发。需要可靠的预后标志物来更好地管理治疗方案。微小RNA（miRNA）是一类长度为19 - 25个核苷酸的非编码小分子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能够更好地预测I期非小细胞肺癌预后的miRNA表达谱。从527例I期非小细胞肺癌患者中提取的miRNA在人类miRNA表达谱v2芯片（Illumina公司）上进行分析。分析其表达谱与癌症亚型、肺癌脑转移以及无复发/无复发生存期（RFS）的相关性。肺腺癌和鳞状细胞癌之间的miRNA表达模式存在显著差异，有171种miRNA不同，包括Let - 7家族成员和miR - 205。鉴定出10种与脑转移相关的miRNA，包括抑制细胞侵袭和转移的miR - 145*。确定了两个对无复发生存期有高度预测性的miRNA特征。第一个包含来自357例I期非小细胞肺癌患者的34种miRNA，与癌症亚型无关，而第二个包含27种miRNA的特征是腺癌特异性的。这两个特征在包含170例I期患者的独立数据集中使用福尔马林固定石蜡包埋和/或新鲜冷冻组织进行了验证。我们的研究结果对I期肺癌患者的治疗具有重要的预后或治疗意义。所鉴定的miRNA作为组织学特异性治疗或复发性疾病预防和治疗的靶点具有巨大潜力。
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.