Chemokine receptor 4 expression is correlated with the occurrence and prognosis of gastric cancer

Abstract

Gastric cancer (GC) is a common tumor with a low 5-year survival rate. The chemokine receptor 4 (CXCR4) protein contributes to the progression and prognosis of GC, but the relationship between CXCR4 and immune infiltration, somatic copy number alteration (SCNA), tumor purity, tumor mutation burden (TMB), cytolytic activity (CYT), and drug sensitivity in GC is poorly understood. This study aimed to systematically explore the role of CXCR4 in GC. Microarray and RNA-seq data were collected from the Gene Expression Omnibus and The Cancer Genome Atlas. Our analysis shows that CXCR4 is correlated with various types of immune cells. Patients with high CXCR4 expression had a higher fraction of B cells and CD8⁺ T cells, and a lower fraction of CD4⁺ T cells. In addition, high CXCR4 expression was associated with more advanced tumor stage, worse prognosis and higher stromal score, immune score, and cytolytic activity (P < 0.05). High CXCR4 expression also correlated with lower tumor purity and TMB. In summary, our analyses suggest that CXCR4 may affect the progression and prognosis of GC by influencing immune infiltration, TMB, CYT, tumor purity, and drug sensitivity.

Keywords: CXCR4; CYT; TMB; gastric cancer; immune infiltration; tumor purity.

Fig. 1

Differential CXCR4 expression. (A) The differential expression of CXCR4 from Oncomine and TIMER; (B) The differential CXCR4 expression in samples from cohort 1 and cohort 2. Data are represented as mean ± SD.

Fig. 2

GO‐BP (top) and KEGG (bottom) analysis. The BP (left) and KEGG (right) enrichment of the differential genes between the CXCR4‐H and CXCR4‐L groups in two cohorts. Circle represents cohort 1, and triangle represents cohort 2. The size of the symbol indicates the gene count; the color indicates the −Log10 of the P value evaluating the statistical significance of the relative enrichment.

Fig. 3

The CXCR4 expression in clinical TNM stage. (A) CXCR4 expression in different stages. (B) CXCR4 expression in different N stages. (C) CXCR4 expression in different T stages. Data are represented as the mean ± SD.

Fig. 4

Comparison of the overall survival curve between the CXCR4‐H and CXCR4‐L groups. Both the log‐rank test and Wilcoxon test were performed for the significance comparison.

Fig. 5

Correlation between CXCR4 expression and immune cells. (A) The correlation between CXCR4 expression and six types of immune cells. (B–G) The validation of the correlation between CXCR4 and gene markers of B‐cell and T‐cell subtypes (Th1, Th2, Tfh, Tregs, and T gamma), macrophages subtypes (M1 and M2), neutrophils, natural killer cells, and dendritic cells (Spearman's correlation).

Fig. 6

Comparison of 6 types of immune cells between the CXCR4‐H and CXCR4‐L groups. *P < 0.05, **P < 0.01, ***P < 0.005.

Fig. 7

Immune infiltration levels with different somatic copy number alterations for the CXCR4 gene. (A) The mRNA level in different types. (B) The infiltration level for each SCNA category is compared with the normal using the two‐sided Wilcoxon rank‐sum test. ***P < 0.001, **P < 0.01, *P < 0.05, .P < 0.1.

Fig. 8

Tumor purity, CYT, and TMB comparison. (A) The comparison of the stromal score in cohort 1 (left) and cohort 2 (right); (B) the comparison of the immune score; (C) the comparison of the tumor purity; (D) the comparison of the CYT; (E) the comparison of log₂TMB in the TCGA samples. Data are represented as the mean ± SD. *P < 0.05, **P < 0.01, ***P < 0.005.

Fig. 9

Correlation between drugs and CXCR4 expression. Pearson correlation was calculated, and red points are the drugs with a significantly increased resistance.