Characterization of the prognostic values of CXCR family in gastric cancer

Abstract

Introduction: The role of CXC chemokine receptors (CXCRs) in gastric cancer (GC) has been an increasing focus. However, comprehensive prognostic values of CXCR members in GC are yet to be clearly defined.

Methods: Multiple public available datasets, including Kaplan-Meier (KM) plotter, oncomine, the cancer genome atlas (TCGA), SurvExpress platform and the tumor immune estimation resource (TIMER), were used for mRNA expression and prognostic characterization. Nomogram method was used for clinical model prediction.

Results: CXCR3, CXCR4 and CXCR5 displayed significantly up-regulated expression in tumor compared to normal. High mRNA expression of CXCR2 (HR = 0.77, 95%CI: 0.62-0.95, p = 0.014), CXCR3 (HR = 0.74, 95%CI: 0.61-0.90, p = 0.0024), CXCR4 (HR = 0.7, 95%CI: 0.58-0.86, p = 0.00048), CXCR5 (HR = 0.72, 95%CI: 0.59-0.87, p = 0.00093) and CXCR6 (HR = 0.66, 95%CI: 0.54-0.81, p = 4.9e-05) was significantly associated with favorable overall survival (OS). The prognostic values of CXCR members were also explored in subtypes, including HER2 status, Lauren classification, pathological stages. The low risk group of CXCR signature displayed a significantly favorable OS compared to the high risk group (HR = 3.22, 95% CI = 2.21-4.69, p = 1.057e-09). Nomogram clinical models were established for both OS (C-index: 0.692; 95%CI: 0.648-0.736) and recurrence free survival (C-index: 0.731; 95%CI: 0.675-0.786). In addition, CXCR6 and CD8+T cells featured the highest correlation (partial-cor = 0.781, p = 4.17e-77).

Conclusion: This study identified distinct expression and prognostic values of CXCR members in GC using public databases.

Keywords: CXCR; Gastric cancer; Prognosis; TCGA.