Prognostic Significance and Immune Correlation of CCL3 Expression in Colon Adenocarcinoma: Insights From...

Colon adenocarcinoma (COAD) remains a leading cause of cancer-related mortality, necessitating reliable prognostic biomarkers. This study explored the potential prognostic role of C-C motif chemokine ligand 3 (CCL3) and its association with immune-related signatures in COAD.

Multiple publicly accessible databases, including TCGA, GEPIA2, UALCAN, TIMER, and Kaplan-Meier (KM) plotter, were used to examine the expression and prognostic profiles of CCL3 in various cancers. The association between CCL3 expression and clinical stage, immune infiltration, and immune gene markers was investigated using TIMER, GEPIA2, and TISIDB databases. Furthermore, we conducted functional enrichment analyses (GO and KEGG) of genes coexpressed with CCL3, assessed methylation status using OncoBD and MEXPRESS, and developed a gene-miRNA interaction network using miRWalk to elucidate their potential roles in COAD.

The expression of CCL3 was significantly upregulated in COAD and most other malignancies. Furthermore, high CCL3 expression was significantly associated with poor overall survival (OS) and relapse-free survival (RFS), with a univariate HR = 1.52 (95% CI: 1.12-2.06, p < 0.01). Multivariate Cox regression confirmed CCL3 as an independent prognostic factor after adjusting for the TNM stage, age, gender, and grade (adjusted HR = 1.42, 95% CI: 1.05-1.92, p = 0.023). CCL3 showed strong positive correlations with immune cell infiltration, particularly macrophages (Cor = 0.72, p < 0.001) and neutrophils (Cor = 0.74, p < 0.001), suggesting its role in shaping an immunosuppressive tumor immune microenvironment (TIME). Additionally, preliminary correlations indicate that high CCL3 may be associated with chemotherapy resistance.

This study suggests that CCL3 could serve as a potential prognostic marker for COAD and other cancers. Because CCL3 expression was strongly associated with immune modulation within the tumor microenvironment, this pointed out that CCL3 could serve as a promising therapeutic target with significant implications for immunotherapy and chemotherapy response.