Risk assessment model and nomogram established by differentially expressed lncRNAs for early-stage lung squamous cell carcinoma

Abstract

Background: The aim of this paper is to identify the differentially expressed lncRNAs (DELs) that could serve as markers for the prognosis of early-stage (stage I-II) lung squamous cell carcinoma (SCC).

Methods: lncRNAs expression data and corresponding clinical information for 395 patients with stage I-II lung SCC were obtained from The Cancer Genome Atlas (TCGA). Univariate Cox regression analysis and LASSO regression were used to screen key lncRNAs, which were then were subjected to a multivariate Cox regression analysis. Furthermore, based on the results of multivariate analysis, lncRNAs with statistical significance were utilized to establish a risk assessment model. Also, a prognostic nomogram based on the risk assessment model was built. These two tools were evaluated by receiver operating characteristic (ROC) curve. Additionally, Kaplan-Meier (KM) survival curves for potential prognostic lncRNAs and clinical factors were performed.

Results: A total of 5 key lncRNAs (AC015712.4, LINC02301, AGAP11, AC099850.3, and AC008915.1) were screened to construct the risk assessment model, and the area under the ROC curves (AUC) showed the model had a general performance. The risk level of the model was identified as an independent prognostic factor for stage I-II lung SCC. A nomogram combining the lncRNA-based risk assessment model, age, and T stage was constructed to predict 3- and 5-year overall survival (OS) in patients with stage I-II lung SCC. The results of ROC and calibration curves demonstrated that the nomogram was reliable in predicting OS rate. Besides, KM survival curves showed OS time was significantly corrected with the expression of AC015712.4, age, and T stage.

Conclusions: In the present study, a risk assessment model and a nomogram based on five lncRNAs were constructed to predict OS time for early-stage lung SCC, which may contribute to the management of lung SCC.

Keywords: Non-small cell lung carcinoma; long noncoding RNA (lncRNA); prognosis; survival.

Figure 1

Identification of key prognostic lncRNAs. (A) Volcano plot of all lncRNAs of stage I–II lung SCC. A total of 2,021 differentially expressed lncRNAs (49 normal vs. 395 tumor tissues) were identified. 1,372 upregulated and 649 downregulated lncRNAs. (B) LASSO coefficient profiles of the 63 lncRNAs identified by univariate Cox regression analysis. (C) Selection of the tuning parameter (λ). The numbers on the top of the figure displayed the candidate lncRNAs counts in LASSO analysis.

Figure 2

Forest plot with hazard ratios from the multivariate Cox regression analysis. Of the 32 key lncRNAs, 5 lncRNAs had a significant effect on the survival of patients with stage I–II lung SCC. AC099850.3 and LINC02301 were poor prognostic factors. AC008915.1, AC015712.4, and AGAP11 were independent predictors of good prognosis in patients with stage I–II lung SCC.

Figure 3

Construction and evaluation of the 5-lncRNA-based risk assessment model. (A) KM survival curves of risk level. OS rate of stage I–II lung SCC patients with high-risk was significantly lower (P=2e-08); (B) receiver operating characteristic (ROC) curves of the risk model. The area under the ROC curves (AUC) =0.69 (3-year survival) and AUC =0.68 (5-year survival).

Figure 4

Construction and assessment of the nomogram. (A) The nomogram for predicting probabilities of 3- and 5-year overall survival (OS) of early-stage lung SCC cancer; (B) receiver operating characteristic (ROC) curves of the nomogram. The area under the ROC curves (AUC) values for 3- and 5-year survival are 0.73 and 0.70, respectively; (C) the calibration plot of the nomogram for 3-year OS; (D) the calibration plot of the nomogram for 5-year OS. SCC, squamous cell carcinoma.

Figure 5

Kaplan-Meier survival curves of OS. (A) Survival curves for AC008915.1 (P value >0.05); (B) survival curves for AC015712.4 (P value <0.01); (C) survival curves for AC099850.3 (P value >0.05); (D) survival curves for AGAP11 (P value >0.05); (E) survival curves for LINC02301 (P value >0.05); (F) survival curves for age (P value <0.01); (G) survival curves for T stage (P value <0.05); (H) survival curves for TNM stage (P value >0.05); (I) survival curves for gender (P value >0.05).