Development and validation of a three-long noncoding RNA signature for predicting prognosis of patients with gastric cancer

Abstract

Background: Gastric cancer (GC) is one of the most frequently diagnosed gastrointestinal cancers throughout the world. Novel prognostic biomarkers are required to predict the prognosis of GC.

Aim: To identify a multi-long noncoding RNA (lncRNA) prognostic model for GC.

Methods: Transcriptome data and clinical data were downloaded from The Cancer Genome Atlas. COX and least absolute shrinkage and selection operator regression analyses were performed to screen for prognosis associated lncRNAs. Receiver operating characteristic curve and Kaplan-Meier survival analyses were applied to evaluate the effectiveness of the model.

Results: The prediction model was established based on the expression of AC007991.4, AC079385.3, and AL109615.2 Based on the model, GC patients were divided into "high risk" and "low risk" groups to compare the differences in survival. The model was re-evaluated with the clinical data of our center.

Conclusion: The 3-lncRNA combination model is an independent prognostic factor for GC.

Keywords: Gastric cancer; Least absolute shrinkage and selection operator; Long noncoding RNA; Prognosis; Survival analysis.

Figure 1

Differentially expressed long noncoding RNAs in The Cancer Genome Atlas-STAndards for development. A: The workflow of the study; B: Volcano plots showing the differentially expressed long noncoding RNAs (DELs) screened with edgeR. The 772 up-regulated DELs are marked in red, and the 220 down-regulated DELs are marked in green; C: Heatmap showing the top 50 DELs in 375 gastric cancer and 32 para-carcinoma tissues. LncRNAs: Long noncoding RNAs; DELs: Differentially expressed long noncoding RNAs; TCGA: The Cancer Genome Atlas; STAD: STAndards for development; COX: Cyclooxygenase; LASSO: Least absolute shrinkage and selection operator; ROC: Receiver operating characteristic.

Figure 2

Least absolute shrinkage and selection operator and COX regression screened prognosis associated long noncoding RNAs. A: Least absolute shrinkage and selection operator coefficient values of the 22 prognosis-related long noncoding RNAs in The Cancer Genome Atlas cohort; B: L1-penalty of least absolute shrinkage and selection operator-COX regression; C: Forest plotshowing the correlations between the 22 long noncoding RNAs and the survival of gastric cancer patients in The Cancer Genome Atlas; D: AC007991.4, AC079385.3, and AL109615.2 are all independent prognostic risk factors for gastric cancer.

Figure 3

Characteristics of the 3-long noncoding RNA combination in The Cancer Genome Atlas queue. A: The Cancer Genome Atlas samples arranged according to risk score (the low-risk group, green, the high-risk group, red); B: The Cancer Genome Atlas samples arranged according to survival time in years (red, death; green, alive); C: Heatmap showing the expression of three long noncoding RNAs in samples according to the risk score (blue, low-risk group; pink, high-risk group); D: The receiver operating characteristic curve for evaluating the predictive effectiveness of the model; E: The high-risk group in this model has a worse overall survival. AUC: Area under the curve.

Figure 4

Expression of AC007991.4, AC079385.3, and AL109615.2 in gastric cancer tissues and cells. A and D: AC007991.4 is weakly expressed in gastric cancer (GC) cells and tissues; B and E: AC079385.3 is overexpressed in GC cells and tissues; C and F: AL109615.2 is overexpressed in GC cells and tissues. ^bP < 0.01. GC: Gastric cancer.

Figure 5

Kaplan-Meier curves for disease-free survival and overall survival. A and B: Disease-free survival (DFS) and overall survival (OS) curves of 200 gastric cancer (GC) patients stratified by AC007991.4 expression (P = 0.05). The overexpression of AC007991.4 contributed to a good survival; C and D: DFS and OS curves of 200 GC patients stratified by AC079385.3 expression (P = 0.00). The overexpression of AC079385.3 contributed to an excellent survival; E and F: DFS and OS curves of 200 GC patients stratified by AL109615.2 expression (P = 0.00 and P = 0.02). The overexpression of AL109615.2 contributed to an excellent survival; G and H: DFS and OS curves of 200 GC patients stratified by the 3-long noncoding RNA model (P = 0.00). The high score of expression model contributed to a good survival. DFS: Disease-free survival; OS: Overall survival.