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Multicenter Study
. 2011 Apr 1;17(7):1875-82.
doi: 10.1158/1078-0432.CCR-10-2961. Epub 2011 Feb 24.

The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts

Motonobu Saito  1 , Aaron J Schetter, Steen Mollerup, Takashi Kohno, Vidar Skaug, Elise D Bowman, Ewy A Mathé, Seiichi Takenoshita, Jun Yokota, Aage Haugen, Curtis C Harris
Affiliations
Multicenter Study

The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts

Motonobu Saito et al. Clin Cancer Res. .

Abstract

Purpose: 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.

Experimental design: 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.

Results: Elevated miR-21 (HR 2.06, 1.13-3.75), miR-17 (HR 2.00, 1.10-3.61), and 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 with 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.

Conclusions: 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.

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Figures

Figure 1
Figure 1
The expression of miR-21 is associated with survival in the Maryland, Norway and Japan cohorts. (A) Kaplan-Meier survival analysis of all stage cases in the Maryland, Norway and Japan cohort stratified by median miR-21 tumor expression. (B) Expression differences of miR-21 between tumor and nontumor in the Maryland and Norway combined cohort and Japan cohort. Dot plots represent miR-21 relative threshold cycle values from qRT-PCR and expression levels in tumor were normalized to nontumor. Relative threshold cycle values greater than 0 in tumor indicate higher expression than that of mean in nontumor log2 scale. Horizontal bars indicate mean expression value. *P < 0.0001, **P = 0.001, ***P = 0.009. Wilcoxon matched-pairs test. (C) Kaplan-Meier survival analysis of TNM stage I cases in the Maryland and Norway combined cohort and Japan cohort stratified by median miR-21 tumor expression.
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