The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts.
The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts.
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DOI：
10.1158/1078-0432.ccr-10-2961
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发表时间：
2011-04-01
期刊：
影响因子：
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通讯作者：
Harris CC
中科院分区：
文献类型：
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作者：
Saito M;Schetter AJ;Mollerup S;Kohno T;Skaug V;Bowman ED;Mathé EA;Takenoshita S;Yokota J;Haugen A;Harris CC
越来越多的证据表明，微小RNA表达的改变与癌症患者的肿瘤进展和生存有关。我们测试了早期肺腺癌中特定的microRNAs的表达是否与预后和疾病进展有关。应用定量RT-PCR方法检测317例来自马里兰、挪威和日本的非小细胞肺癌(NSCLC)组织中miR-21、miR-17和miR-155的表达。Kaplan Meier和Cox回归分析评估了microRNA表达与癌症特异性死亡率和无病生存期之间的关系。在马里兰州的队列中，miR-21(风险比[HR]2.06，1.13-3.75)、miR-17(HR 2.00，1.10-3.61)、miR-155(HR 2.37，1.27-4.42)升高与更差的癌症特异性死亡率相关。在另外两个队列中进行了评估，只有miR-21与挪威队列中较差的癌症特异性死亡率(HR 2.78，1.22-6.31)和日本队列中较差的无复发生存率(HR 2.82，1.57-5.07)有关。与TNM I期肿瘤相比，进展期肿瘤miR-21的表达水平显著升高。单独评估TNM I期患者，miR-21水平高与肿瘤特异性死亡率(HR 2.16，1.11-4.21)和无复发生存率(3.40，1.57-7.36)相关，而与其他临床因素无关。这是第一次报道miR-21表达增加与I期肺癌的疾病进展和生存有关的研究。提示miR-21的表达可能与肺癌的发生有关，可作为肺腺癌的治疗靶点或早期预后的生物标志物。
There is increasing evidence that altered microRNA expression is associated with tumor progression and survival in cancer patients. We tested if the expression of specific microRNAs was associated with prognosis and disease progression in early stage lung adenocarcinoma. The expression of miR-21, miR-17 and miR-155 was measured by quantitative RT-PCR in tissues from 317 non small cell lung cancer (NSCLC) patients that originated from Maryland, Norway and Japan. Kaplan Meier and Cox regression analysis evaluated associations of microRNA expression with cancer-specific mortality and disease free survival. Elevated miR-21 (hazard ratio [HR] 2.06, 1.13–3.75), miR-17 (HR 2.00, 1.10–3.61), miR-155 (HR 2.37, 1.27–4.42) was associated with worse cancer-specific mortality in the Maryland cohort. These were evaluated in two additional cohorts and only miR-21 was associated with worse cancer-specific mortality in the Norwegian cohort (HR 2.78, 1.22–6.31) and worse relapse free survival in the Japanese cohort (HR 2.82, 1.57–5.07). More advanced stage tumors expressed significantly higher levels of miR-21 compared to TNM stage I tumors. TNM stage I patients were evaluated separately and high levels of miR-21 was associated with worse cancer-specific mortality (HR 2.16, 1.11–4.21) and relapse-free survival (3.40, 1.57–7.36) independent of other clinical factors. This is the first study to report that increased miR-21 expression is associated with disease progression and survival in stage I lung cancer. This suggests that expression of miR-21 may contribute to lung carcinogenesis and serve as a therapeutic target or early stage prognostic biomarker for lung adenocarcinoma.