Construction and Validation of a Universal Applicable Prognostic Signature for Gastric Cancer Based on Seven Immune-Related Gene Correlated With Tumor Associated Macrophages.

Background: Tumor-associated macrophages (TAMs) play a critical role in the progression of malignant tumors, but the detailed mechanism of TAMs in gastric cancer (GC) is still not fully explored.

Methods: We identified differentially expressed immune-related genes (DEIRGs) between GC samples with high and low macrophage infiltration in The Cancer Genome Atlas datasets. A risk score was constructed based on univariate Cox analysis and Lasso penalized Cox regression analysis in the TCGA cohort (n=341). The optimal cutoff determined by the 5-year time-dependent receiver operating characteristic (ROC) curve was considered to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE84437, n=431; GSE62254, n=300; GSE15459, n=191; and GSE26901, n=109) from the Gene Expression Omnibus (GEO) database.

Results: The signature consisting of 7 genes (FGF1, GRP, AVPR1A, APOD, PDGFRL, CXCR4, and CSF1R) showed good performance in predicting overall survival (OS) in the 5 independent cohorts. The risk score presented an obviously positive correlation with macrophage abundance (cor=0.7, p<0.001). A significant difference was found between the high- and low-risk groups regarding the overall survival of GC patients. The high-risk group exhibited a higher infiltration level of M2 macrophages estimated by the CIBERSORT algorithm. In the five independent cohorts, the risk score was highly positively correlated with the stromal cell score, suggesting that we can also evaluate the infiltration of stromal cells in the tumor microenvironment according to the risk score.

Conclusion: Our study developed and validated a general applicable prognostic model for GC from the perspective of TAMs, which may help to improve the precise treatment strategy of GC.