Use of MicroRNA Expression Levels to Predict Outcomes in Resected Stage I Non-small Cell Lung Cancer
Use of MicroRNA Expression Levels to Predict Outcomes in Resected Stage I Non-small Cell Lung Cancer
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DOI：
10.1097/jto.0b013e3181f3909d
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发表时间：
2010-11-01
影响因子：
20.4
通讯作者：
Pfeifer, John
中科院分区：
文献类型：
--
作者：
Duncavage, Eric;Goodgame, Boone;Pfeifer, John
背景：尽管接受了根治性切除，但仍有近三分之一的 I 期非小细胞肺癌 (NSCLC) 患者死于复发性疾病。对于已切除的 I 期 NSCLC 患者的复发，尚无可靠的临床或分子预测因子。识别手术切除后有复发风险的患者是当今的重要挑战之一。 MicroRNA (miRNA) 调节数百个对于维持癌症表型至关重要的基因。方法：在一项探索性研究中，我们确定了先前报道的与各种人类恶性肿瘤的侵袭性或结果相关的 6 种 miRNA（let-7a、miR-7、miR-21、miR-155、miR-210 和 miR-221）的表达是否与已切除的 I 期 NSCLC 患者的肿瘤复发相关。我们测量了 46 名手术切除的 T1 或 T2 I 期 NSCLC 患者的福尔马林固定、石蜡包埋的肿瘤组织和匹配的正常肺组织中这些 miRNA 的表达。结果：平均三次数据显示，复发的肿瘤的 miR-221 表达比未复发的肿瘤低 0.14 倍 (p = 0.0036)。此外，与同一患者的相邻正常肺相比，肿瘤组织中 miR-221 的增加也与不复发相关 (p = 0.0011)。对 miR-221 调节的选定下游靶基因（特别是 CDKN1B、CDKN1C、paralemmin-2 和 CXCL12）的表达进行平行测量，结果显示，在无复发性疾病的患者肿瘤中，CDKN1C 几乎显着下调（p = 0.0522），与同一组中 miR-221 活性增加一致。 结论：如果在前瞻性研究中得到证实，切除的 NSCLC 中的 miRNA 表达可以潜在地识别出手术后复发风险高的人。
Background: Despite undergoing curative resection, nearly a third of patients with stage I non-small cell lung cancer (NSCLC) die of recurrent disease. There are no reliable clinical or molecular predictors of relapse in patients with resected stage I NSCLC. Identifying patients at risk for relapse after surgical resection is one of the important challenges today. MicroRNAs (miRNAs) regulate hundreds of genes central to maintaining a cancer phenotype.Methods: In an exploratory study, we determined whether expression of six miRNAs (let-7a, miR-7, miR-21, miR-155, miR-210, and miR-221) previously reported to correlate with invasiveness or outcome in various human malignancies were associated with tumor recurrence in patients with resected stage I NSCLC. We measured expression of these miRNAs in formalin-fixed, paraffin-embedded tissue from both tumor and matched normal lung in a set of 46 patients with surgically resected T1 or T2 stage I NSCLC.Results: Averaged triplicate data showed that tumors which recurred had 0.14-fold lower miR-221 expression than those which did not recur (p = 0.0036). In addition, increased miR-221in tumor tissue when compared with adjacent normal appearing lung in the same patient also correlated with nonrecurrence (p = 0.0011). Parallel measurement of expression of selected downstream target genes regulated by miR-221, specifically, CDKN1B, CDKN1C, paralemmin-2, and CXCL12, showed a near significant (p = 0.0522) down-regulation of CDKN1C in tumors of patients with no recurrent disease, consistent with increased miR-221 activity in the same group.Conclusion: If confirmed in prospective studies, miRNA expression in resected NSCLC could potentially identify those at high risk of relapse after surgery.