Study on correlation between CXCL13 and prognosis and immune characteristics of ovarian cancer

Abstract

Ovarian cancer (OC) has a limited immunotherapeutic response; hence, this study aimed to investigate the relationship between CXC-chemokine ligand 13 (CXCL13) expression and overall survival (OS) rate, key immune pathways, degree of immune cell infiltration, and progressive disease (PD)-1 checkpoint blockade. A total of 703 differentially expressed genes were obtained from "The Cancer Genome Atlas" (TCGA) database based on the immune and stromal scores of 379 OC patients for getting the targeted gene CXCL13. The association between CXCL13 and OS in OC patients, biological function annotation of CXCL13, and its correlation with immune components were assessed. The results indicated that upregulated CXCL13 expression was positively correlated with better OC patient prognosis. CXCL13 expression was associated with 6 immune-related pathways, 10 immune cells, and PD-1 expression of OC micro-environment. Moreover, high expression of CXCL13 was related to a better tumor response and more extended tumor-stable stage after PD-1 blocking therapy in IMvigor210. The study concluded that CXCL13 could be a prognostic marker and a potential immunotherapy target for OC patients, especially PD-1 checkpoint blockade.

Figure 1.

Research design overview.

Figure 2.

Venn diagram of upregulated (A) and downregulated (B) differentially expressed genes screened based on immune and stromal scores. The most pronounced up and downregulated 50 differentially expressed genes of the immune score group (C) and stromal score group (D).

Figure 3.

Enrichment analysis of differentially expressed genes. Red represents up-regulation in certain pathways, while blue represents down-regulation. (A) The bubble graph of gene ontology (GO) functional enrichment analysis; (B) the circle graph of GO functional enrichment analysis; (C) the bubble graph of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis; (D) the circle graph of KEGG pathway-enrichment analysis.

Figure 4.

(A) Protein–protein intersection (PPI) network of differentially expressed genes (DEGs); (B) twenty core genes in the PPI network; (C) prognostic DEGs; (D) core genes CXCL13 and CD3E on the Venn diagram; (E) meta-analysis for OS based on expression levels of CXCL13 in OC patients.

Figure 5.

TCGA and GETx datasets show expression of CXCL13 is statistical different between OC and normal tissue (A) and in different pathological stages of OC (B). (C) Oncomine database verifies the expression of CXCL13; (D) the negative staining of CXCL13 in 2 normal tissues; (E) the negative (0), low (1), and medium (2) immunohistochemical staining of CXCL13 in 3 OC patients.

Figure 6.

Survival curves of OC patients in CXCL13 high- and low-expression groups.

Figure 7.

Gene set enrichment analysis enrichment pathway of CXCL13 expression profile in OC patients.

Figure 8.

Correlation between the expression of CXCL13 and infiltration of various immune cell components in the tumor microenvironment. (A) CD8⁺ T cell; (B) activated CD4⁺ memory T cell; (C) memory B cell; (D) M1 macrophage cell; (E) follicular helper T cell; (F) resting CD4⁺ memory T cell; (G) naive B cell; (H) M2 macrophage cell; (I) activated myeloid dendritic cell; (J) neutrophils.

Figure 9.

(A) Correlation between the expression of CXCL13 and PD-1 of TCGA-OC samples; (B) correlation between the expression of CXCL13 and CR/PR, SD/PD in mUC samples after receiving PD-L1 blocking therapy (CR = complete response, PR = partial response, PD = progressive disease, SD = stable disease). Survival curves of mUC patients with high- and low-CXCL13 expression in SD/PD (C) and CR/PR (D) group.