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An eleven-lncRNA signature predicts overall survival in patients with gastric cancer
Background
Gastric cancer (GC) is one of the most common malignancies worldwide. Multidisciplinary strategies including chemotherapy, radiotherapy and surgical resection are the basic treatment for stomach cancer and significantly improve the survival of patients with GC. However, the prognosis of patients with advanced GC remains poor. The high risk of disease relapse prompted the investigation of genomic factors which could be the predictive or prognostic biomarkers of GC. Thus, we established a multi-gene prognostic model for predicting the prognosis of GC and explored crucial molecular mechanisms associated with prognostic lncRNA expression signature.
Methods
In this study, we collected lncRNAs expression profiling to identify prognosis related lncRNAs for GC from TCGA database. In addition, we developed a lncRNA signature-based risk score to comprehensively assess the prognostic function of lncRNA. Furthermore, we performed a ROC analysis to identify the optimal cut-off point for classification risk level of the patients. Univariate Cox regression models were used to assess the association between lncRNAs and prognosis of patients with GC. lncRNA signature-based risk score was developed based on the Cox co-efficient of the individual lncRNAs. The prognostic value of this risk score was validated in the complete set and internal testing set. A co-expression network between genes and lncRNAs was also constructed to identify lncRNAs co-expressed with genes to explore crucial molecular mechanisms associated with prognostic lncRNA expression signature.
Results
In summary, a 11-lncRNAs expression signature (RP11-110I1.13, CTD-2144E22.5, CTD-2263F21.1, NBAT1, RP11-542B15.1, RSF1-IT2, RP1-150O5.3, RP11-2H3.6, RP3-449M8.6, RP11-327F22.6, RP11-342D11.2) were identified and validated. The signature significantly differentiated high- and low-risk patients with regard to overall survival in TCGA testing set (n=171) (HR=2.90, 95% CI 1.12-7.52; p=0.028) and TCGA complete set (n=343) (HR=6.26, 95% CI 2.5-15.64; p=0.000). The potential functions of this 11-lncRNA expression signature and individual lncRNAs as prognostic targets of GC were revealed by this study. KEGG pathway enrichment analysis and GSEA showed that these four co-expressed modules participate in different pathways, and many of these pathways are associated with the development and progression of disease.
Conclusions
This 11 validated lncRNAs might be used to predict the prognosis of gastric patients. Furthermore, these findings may have important implications in the understanding of the potential mechanisms in development and progression of disease.
Legal entity responsible for the study
The authors.
Funding
This study was funded by the Sichuan Province Science and Technology Support Program (CN) (Grant No. 2020YFS0234, 2020YFS0233) and 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC18034).
Disclosures
All authors have declared no conflicts of interest.
