Expression profiling, molecular subtyping and prognostic signature construction of chemokines and chemokine receptors in gastric cancer.

Background: Gastric cancer (GC) is a highly heterogeneous malignancy of the digestive tract, with significant variations in treatment response and clinical prognosis depending on its molecular subtypes. Chemokines and chemokine receptors (CCRs) have been implicated in GC initiation and progression, yet the precise mechanisms underlying their role remain poorly defined. This study mainly focused on a systematic investigation of CCRs in GC is of critical clinical and scientific importance. Methods: We comprehensively analyzed the transcriptional profiles and mutational landscape of CCRs in GC and constructed a CCR-related prognostic signature. The Cancer Genome Atlas (TCGA) cohort (371 GC samples) served as the training set, and the GSE84437 dataset was used as the validation cohort. Consensus clustering based on CCR gene expression was performed for patient stratification. A prognostic risk model was developed using a stepwise approach combining univariate Cox regression, the least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Correlations between the risk score, tumor mutation burden (TMB), and immunotherapy response were also evaluated. Results: We identified 25 significantly upregulated and 12 significantly downregulated CCR genes in GC tissues. Consensus clustering based on CCR expression effectively stratified patients into subgroups with distinct prognoses and tumor microenvironment (TME) characteristics. A 9-gene prognostic signature, including four novel genes ( Conclusions: Our study provides novel insights into the biological roles of CCRs in GC. We propose a CCR-based molecular stratification strategy and a prognostic signature that may serve as a complementary tool for risk assessment in GC patients, pending further prospective validation.