Abstract
BackgroundStromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC).MethodsWe identified differential expressed immune-related genes (DEIRGs) between the high- and low-stromal cell abundance GC samples in The Cancer Genome Atlas and GSE84437 datasets. A risk score was constructed basing on univariate cox regression analysis, LASSO regression analysis, and multivariate cox regression analysis in the training cohort (n=772). The median value of the risk score was used to classify patients into groups with high and low risk. We conducted external validation of the prognostic signature in four independent cohorts (GSE26253, n=432; GSE62254, n=300; GSE15459, n=191; GSE26901, n=109) from the Gene Expression Omnibus (GEO) database. The immune cell infiltration was quantified by the CIBERSORT method.ResultsThe risk score contained 6 genes (AKT3, APOD, FAM19A5, LTBP3, NOV, and NOX4) showed good performance in predicting 5-year overall survival (OS) rate and 5-year recurrence-free survival (RFS) rate of GC patients. The risk death and recurrence of GC patients growing with the increasing risk score. The patients were clustered into three subtypes according to the infiltration of 22 kinds of immune cells quantified by the CIBERSORT method. The proportion of cluster A with the worst prognosis in the high-risk group was significantly higher than that in the low-risk group; the risk score of cluster C subtype with the best prognosis was significantly lower than that of the other two subtypes.ConclusionThis study established and validated a robust prognostic model for gastric cancer by integrated analysis 1804 samples of six centers, and its mechanism was explored in combination with immune cell infiltration characterization.
Highlights
Stromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC)
Stromal cells are the main component of Tumor microenvironment (TME), including angiogenic vascular cell (AVC), Huo et al World Journal of Surgical Oncology (2022) 20:4 cancer-associated fibroblast (CAF), and cancer-associated adipocyte cell (CAA) [2], which is closely related to the occurrence, development, invasion, and metastasis of the tumor [3, 4]
The higher stromal score associated with poor prognosis of GC The GC patients with higher stromal score who had unfavorable clinical outcome were observed in the two large sample and independent cohorts (Fig. 2A, C)
Summary
Stromal cells in tumor microenvironment could promote immune escape through a variety of mechanisms, but there are lacking research in the field of gastric cancer (GC). Stromal cells have been paid growing attention as a potential therapeutic target to effectively inhibit the progression of cancer [5,6,7]. With the emergence of new treatments such as targeted therapy and immunotherapy [11, 12], the overall prognosis of GC has been greatly improved, but it is still unsatisfactory, and the conventional TNM staging is difficult to accurately evaluate the prognosis of GC after surgery, so developing an effective prognostic evaluation scheme has always been a research hotspot in the field of GC
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