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Construction and Validation of a Novel Prognostic Signature for Intestinal Type of Gastric Cancer
27 Pages Posted: 27 Jan 2021
More...Abstract
Background: Intestinal type of gastric cancer (IGC) is the largest subtype of gastric cancer (GC). The purpose was to construct a prognostic signature for IGC patients to improve the prognostic accuracy.
Methods: The microarray datasets and associated clinical characteristics of HGD and IGC were obtained from the Gene Expression Omnibus (GEO) database. Based on the differential expression analysis between HGD and IGC, the prognostic related differential expression genes (DEGs) were identified in a training group by univariate COX regression analysis. The least absolute shrinkage and selection operator (LASSO) regression was used to construct an optimal prognostic signature. The enrichment analysis was performed by using Gene Set Enrichment Analysis (GSEA). The performance of the nomogram was assessed by the calibration curve and concordance index (C-index). The results were validated by using a testing group.
Findings: We identified 35 prognostic related DGEs in the training cohort. The nine-gene signature was established by LASSO analysis. The nine-gene signature was an independent risk factor in both the training and testing cohorts. In GSEA analysis, the gene expression in high-risk group was enriched in hedgehog signaling, epithelial mesenchymal transition, and angiogenesis. The nomogram for IGC showed good performance with C-index of 0.81 (95%CI: 0.76-0.86) and 0.70 (95%CI: 0.63-0.77) in the training and testing cohorts, respectively.
Interpretation: We identified and verified a nine-gene signature for the prognostic prediction of IGC patients, which might identify subgroups of IGC patients and select more suitable therapeutic options.
Funding Statement: The present study was supported by the National Natural Science Foundation of China (grant NO. 31770537), International S & T Cooperation Program of China (grant NO. 2015DFA31650); International S & T Cooperation Program of Gansu Province (grant NO. 18YF1WA113), Special Research Project of Lanzhou University Serving the Economic and Social Development of Gansu Province (grant NO. 054000282).
Declaration of Interests: The authors declare that there is no conflict of interest.
Keywords: Intestinal type of gastric cancer, high grade dysplasia, prognostic value, nomogram
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