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. 2011 Sep 15:11:393.
doi: 10.1186/1471-2407-11-393.

Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study

Wangyu Zhu  1 , XiaoGuang Liu, JianYing He, DongDong Chen, YanYan Hunag, Yong Kui Zhang
Affiliations

Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study

Wangyu Zhu et al. BMC Cancer. .

Abstract

Background: Lung cancer is the leading cause of cancer-related deaths worldwide. Early detection is considered critical for lung cancer treatment. MicroRNAs (miRNAs) have shown promise as diagnostic and prognostic indicators. This study was to identify specific miRNAs with diagnostic and prognostic value for patients with lung cancer, and to explore the correlation between expression profiles of miRNAs and patient survival.

Methods: Gene expression of members of the miR-183 family (miR-96, miR-182, and miR-183) were examined in 70 paired samples from lung cancer patients (primary cancer and non-cancerous tissues and sera), as well as 44 serum samples from normal volunteers and lung cancer cell lines by quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR). The correlation between the expression of miRNAs in tissues, sera, and patient overall survival were also examined by log-rank and Cox regression analysis.

Results: Expression levels of members of the miR-183 family in lung cancer tumor and sera were higher than that of their normal counterparts. The miR-96 expression in tumors was positively associated with its expression in sera. Log-rank and Cox regression analyses demonstrated that high expression of tumor and serum miRNAs of the miR-183 family were associated with overall poor survival in patients with lung cancer.

Conclusions: Our results suggest that the expressions of miR-96, miR-182, and miR-183 in tumor and sera may be considered potential novel biomarkers for the diagnosis and prognosis of lung cancer.

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Figures

Figure 1
Figure 1
RT-qPCR analysis of miRNAs in lung carcinoma and matched noncancerous tissues. (A) Paired sample t-test was used to compare the differential expressions of miR-96, miR-182, and miR-183 in 70 lung carcinoma and matched noncancerous tissues. The P-values for miR-96, miR-182, and miR-183 were P <0.0001 for each. (B) Unpaired sample t-test was used to compare the differential expressions of miR-96, miR-182, and miR-183 in sera from 70 lung cancer patients and 44 healthy controls. The P-values for miR-96, miR-182, and miR-183 were P <0.0001, = 0.0130, and = 0.0086, respectively. *Indicates a significant difference between groups (P < 0.05).
Figure 2
Figure 2
Correlation between the expressions of miR-96, miR-182, and miR-183 in tissues vs. sera from lung cancer patients. Pearson's correlation between the expression of miR-96, miR-182, and miR-183 in NSCLC tissues and sera are shown. The correlation rate of miR-96 was 0.419, P = 0.0003; miR-182 was 0.0464, P = 0.703; and miR-183 was 0.118, P = 0.332.
Figure 3
Figure 3
RT-qPCR analysis of lung cancer cell lines. Total RNA was isolated from several different lung cancer cells lines by the Trizol method (Invitrogen) according to the manufacturer's instructions, and qRT-PCR was performed using TaqMan MicroRNA Assay Kits (Applied Biosystems). The average expression levels of miR-96, miR-182, and miR-183 in tissues and sera were normalized using the 2-ΔΔCt method relative to the average of U6 snRNA and U48 snRNA. The average Ct value of triplicates in three candidate miRNAs was calculated. *Indicates a significant difference compared to HBE cells (P < 0.05).
Figure 4
Figure 4
Correlation of expression of miR-183 family with clinical-pathological features of lung cancer. The Mann-Whitney U-test was used to examine the correlation between miR-183 family levels and clinical-pathological features. The results showed that (A) Tumor miR-96, miR-182, and miR-183, and serum miR-96 expression were higher in squamous-cell lung carcinoma than in adenocarcinoma (P = 0.0216, 0.0190, 0.0042, and 0.0310, respectively). (B) Tumor miR-183 expression was higher in NSCLC patients with lymph node metastasis than without lymph node metastasis (P = 0.0086). (C) Tumor miR-182 and miR-183 expressions were higher in NSCLC patients with tumor invasion to lung membrane than without invasion to lung membrane (P = 0.0222 and 0.0140, respectively). (D) Tumor and serum miR-182 levels were higher in NSCLC patients with tumor size > 3 cm than those with tumor size < 3 cm (P = 0.0464 and 0.0351, respectively). (E) Tumor miR-183 expression was higher in stages II, III, and IV NSCLC samples than in stage I. Differences were significant after the Mann Whitney U-test. *Indicates a significant difference between groups (P < 0.05).
Figure 5
Figure 5
Kaplan-Meier survival curves for NSCLC patients plotted for tumor and serum miR-96, miR-182, and miR-183. Kaplan-Meier survival curves for NSCLC patients based on the median level of fold change. The P-value was calculated using the log-rank test between patients with high- and low-fold changes. Overall survival of patients with high vs. low miR-183 family expression levels are shown. P < 0.05 indicates a significant difference between groups.
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