Clinical significance and prospective molecular mechanism of C‑C motif chemokine receptors in patients with early‑stage pancreatic ductal adenocarcinoma after pancreaticoduodenectomy.

Abstract

The present study aimed to determine the clinical significance and potential molecular mechanisms of C-C motif chemokine receptor (CCR) genes in patients with early-stage pancreatic ductal adenocarcinoma (PDAC). The transcriptomic, survival and clinical data of 112 patients with early-stage PDAC who underwent pancreaticoduodenectomy were obtained from The Cancer Genome Atlas. The prognostic values of the CCR genes involved in early-stage PDAC were evaluated using Kaplan-Meier analysis and the multivariate Cox proportional risk regression model, and the potential molecular mechanisms were determined using bioinformatics tools. The identified CCRs closely interacted with each other at both the gene and protein levels. High expression levels of CCR5 [adjusted P=0.012; adjusted hazard ration (HR)=0.478, 95% confidence interval (CI)=0.269–0.852], CCR6 (adjusted P=0.026; adjusted HR=0.527, 95% CI=0.299–0.927) and CCR9 (adjusted P=0.001; adjusted HR=0.374, 95% CI=0.209–0.670) were significantly associated with longer overall survival times in patients with early-stage PDAC. The contribution of CCR5, CCR6 and CCR9 to the outcome of early-stage PDAC was also demonstrated. Combined survival analysis of CCR5, CCR6 and CCR9 suggested that patients with high expression levels of these CCRs exhibited the most favorable outcomes. A prognostic signature was constructed in terms of the expression level of CC5, CCR6 and CCR9, and time-dependent receiver operating characteristic curves indicated that this signature was able to effectively predict the outcome of patients with early-stage PDAC. The potential molecular mechanisms of CCR5, CC6 and CCR9 in PDAC include its intersection of the P53, nuclear factor (NF)-κB, generic transcription, mitogen-activated protein kinase and STAT signaling pathways. Collectively, this highlights that CCR5, CCR6 and CCR9 are potential prognostic biomarkers for early-stage PDAC.