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A potential signature of eight long non-coding RNAs predicts survival in patients with non-small cell lung cancer.

Zhou M, Guo M, He D, Wang X, Cui Y, Yang H, Hao D, Sun J - J Transl Med (2015)

Bottom Line: With the eight-lncRNA signature, patients of the training dataset could be classified into high- and low-risk groups with significantly different OS (median survival 1.67 vs. 6.06 years, log-rank test p = 4.33E-09).Multivariate regression and stratified analysis suggested that the prognostic power of the eight-lncRNA signature was independent of clinical and pathological factors.Functional enrichment analyses revealed potential functional roles of the eight prognostic lncRNAs in tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, People's Republic of China. biofomeng@hotmail.com.

ABSTRACT

Background: Accumulated evidence suggests that dysregulated expression of long non-coding RNAs (lncRNAs) may play a critical role in tumorigenesis and prognosis of cancer, indicating the potential utility of lncRNAs as cancer prognostic or diagnostic markers. However, the power of lncRNA signatures in predicting the survival of patients with non-small cell lung cancer (NSCLC) has not yet been investigated.

Methods: We performed an array-based transcriptional analysis of lncRNAs in large patient cohorts with NSCLC by repurposing microarray probes from the gene expression omnibus database. A risk score model was constructed based on the expression data of these eight lncRNAs in the training dataset of NSCLC patients and was subsequently validated in other two independent NSCLC datasets. The biological implications of prognostic lncRNAs were also analyzed using the functional enrichment analysis.

Results: An expression pattern of eight lncRNAs was found to be significantly associated with overall survival (OS) of NSCLC patients in the training dataset. With the eight-lncRNA signature, patients of the training dataset could be classified into high- and low-risk groups with significantly different OS (median survival 1.67 vs. 6.06 years, log-rank test p = 4.33E-09). The prognostic power of eight-lncRNA signature was further validated in other two non-overlapping independent NSCLC cohorts, demonstrating good reproducibility and robustness of this eight-lncRNA signature in predicting OS of NSCLC patients. Multivariate regression and stratified analysis suggested that the prognostic power of the eight-lncRNA signature was independent of clinical and pathological factors. Functional enrichment analyses revealed potential functional roles of the eight prognostic lncRNAs in tumorigenesis.

Conclusions: These findings indicate that the eight-lncRNA signature may be an effective independent prognostic molecular biomarker in the prediction of NSCLC patient survival.

No MeSH data available.


Related in: MedlinePlus

The eight-lncRNA signature-focused risk score in prognosis of overall survival in additional validation datasets. a Kaplan–Meier survival curves were plotted for GSE31210 (n = 226). b The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE31210. c Kaplan–Meier survival curves were plotted for GSE50081 (n = 181). d The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE50081.
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Fig2: The eight-lncRNA signature-focused risk score in prognosis of overall survival in additional validation datasets. a Kaplan–Meier survival curves were plotted for GSE31210 (n = 226). b The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE31210. c Kaplan–Meier survival curves were plotted for GSE50081 (n = 181). d The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE50081.

Mentions: To validate the prognostic power of the eight-lncRNA signature for survival prediction, the constructed expression-defined lncRNA prognostic model was also evaluated in the testing GSE31210 dataset. The same prognostic risk score model obtained from the training dataset was used to calculate the eight-lncRNA signature-based risk scores for 226 patients in the entire GSE31210 dataset. The cutoff value of the risk score derived from the training dataset without re-estimating parameters was used for the testing dataset to classify the patients into either a high-risk group (n = 111) or a low-risk group (n = 115). Patients with high-risk scores exhibited poorer OS than those with low-risk scores (median OS 4.45 vs. 5.08 years, log-rank test p = 1.65E−03). Kaplan–Meier curves for the high- and low-risk groups in the testing dataset are shown in Figure 2a. The OS rate of patients in the high-risk group was 91.7% at 2 years and 78.7% at 4 years, versus 97.4 and 91.5% in the low-risk group, respectively. A significant association between the eight-lncRNA signature risk score and OS in the univariable Cox regression model was observed. The hazard ratios of the eight-lncRNA signature risk scores of the high-risk group versus the low-risk group for OS was 3.067 (p = 0.003; 95% CI 1.471–6.395; Table 3).Figure 2


A potential signature of eight long non-coding RNAs predicts survival in patients with non-small cell lung cancer.

Zhou M, Guo M, He D, Wang X, Cui Y, Yang H, Hao D, Sun J - J Transl Med (2015)

The eight-lncRNA signature-focused risk score in prognosis of overall survival in additional validation datasets. a Kaplan–Meier survival curves were plotted for GSE31210 (n = 226). b The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE31210. c Kaplan–Meier survival curves were plotted for GSE50081 (n = 181). d The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE50081.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4504221&req=5

Fig2: The eight-lncRNA signature-focused risk score in prognosis of overall survival in additional validation datasets. a Kaplan–Meier survival curves were plotted for GSE31210 (n = 226). b The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE31210. c Kaplan–Meier survival curves were plotted for GSE50081 (n = 181). d The eight lncRNA-based risk score distribution, patients’ survival status and heatmap of the eight lncRNA expression profiles were analyzed in the GSE50081.
Mentions: To validate the prognostic power of the eight-lncRNA signature for survival prediction, the constructed expression-defined lncRNA prognostic model was also evaluated in the testing GSE31210 dataset. The same prognostic risk score model obtained from the training dataset was used to calculate the eight-lncRNA signature-based risk scores for 226 patients in the entire GSE31210 dataset. The cutoff value of the risk score derived from the training dataset without re-estimating parameters was used for the testing dataset to classify the patients into either a high-risk group (n = 111) or a low-risk group (n = 115). Patients with high-risk scores exhibited poorer OS than those with low-risk scores (median OS 4.45 vs. 5.08 years, log-rank test p = 1.65E−03). Kaplan–Meier curves for the high- and low-risk groups in the testing dataset are shown in Figure 2a. The OS rate of patients in the high-risk group was 91.7% at 2 years and 78.7% at 4 years, versus 97.4 and 91.5% in the low-risk group, respectively. A significant association between the eight-lncRNA signature risk score and OS in the univariable Cox regression model was observed. The hazard ratios of the eight-lncRNA signature risk scores of the high-risk group versus the low-risk group for OS was 3.067 (p = 0.003; 95% CI 1.471–6.395; Table 3).Figure 2

Bottom Line: With the eight-lncRNA signature, patients of the training dataset could be classified into high- and low-risk groups with significantly different OS (median survival 1.67 vs. 6.06 years, log-rank test p = 4.33E-09).Multivariate regression and stratified analysis suggested that the prognostic power of the eight-lncRNA signature was independent of clinical and pathological factors.Functional enrichment analyses revealed potential functional roles of the eight prognostic lncRNAs in tumorigenesis.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, People's Republic of China. biofomeng@hotmail.com.

ABSTRACT

Background: Accumulated evidence suggests that dysregulated expression of long non-coding RNAs (lncRNAs) may play a critical role in tumorigenesis and prognosis of cancer, indicating the potential utility of lncRNAs as cancer prognostic or diagnostic markers. However, the power of lncRNA signatures in predicting the survival of patients with non-small cell lung cancer (NSCLC) has not yet been investigated.

Methods: We performed an array-based transcriptional analysis of lncRNAs in large patient cohorts with NSCLC by repurposing microarray probes from the gene expression omnibus database. A risk score model was constructed based on the expression data of these eight lncRNAs in the training dataset of NSCLC patients and was subsequently validated in other two independent NSCLC datasets. The biological implications of prognostic lncRNAs were also analyzed using the functional enrichment analysis.

Results: An expression pattern of eight lncRNAs was found to be significantly associated with overall survival (OS) of NSCLC patients in the training dataset. With the eight-lncRNA signature, patients of the training dataset could be classified into high- and low-risk groups with significantly different OS (median survival 1.67 vs. 6.06 years, log-rank test p = 4.33E-09). The prognostic power of eight-lncRNA signature was further validated in other two non-overlapping independent NSCLC cohorts, demonstrating good reproducibility and robustness of this eight-lncRNA signature in predicting OS of NSCLC patients. Multivariate regression and stratified analysis suggested that the prognostic power of the eight-lncRNA signature was independent of clinical and pathological factors. Functional enrichment analyses revealed potential functional roles of the eight prognostic lncRNAs in tumorigenesis.

Conclusions: These findings indicate that the eight-lncRNA signature may be an effective independent prognostic molecular biomarker in the prediction of NSCLC patient survival.

No MeSH data available.


Related in: MedlinePlus