Integrative Single-Cell Transcriptomics Identifies CCL18 as Target in Prostate Cancer

Background: Prostate adenocarcinoma (PRAD) remains a major cause of cancer morbidity in men, driven by cellular heterogeneity and immune evasion. Single-cell RNA sequencing (scRNA-seq) enables high-resolution profiling of tumor and immune states to uncover cell-specific therapeutic targets. This study integrates scRNA-seq, pathway enrichment, and molecular docking to identify immunomodulatory molecules with therapeutic potential in prostate cancer. Methods: scRNA-seq data (GSE181294) from 34 PRAD and 5 normal samples (165,905 cells) were processed in Seurat for quality control, clustering, and annotation. Differential expression analyses across tumor, epithelial, and immune compartments were followed by GO/KEGG enrichment and pseudobulk validation. Expression and survival associations were evaluated using TCGA-PRAD via UALCAN. Candidate genes were prioritized through cell-cell communication modeling and validated in silico using structure-based molecular docking with curated ligand libraries. Results: Seven major cell clusters were identified. Tumor cells showed enrichment of mitotic and chemokine pathways, while T/NK cells exhibited immune-suppressive signatures. CCL18 emerged as a key chemokine overexpressed across tumor and immune compartments and validated in TCGA data. Communication analysis identified CCL18-producing cluster 0 signaling through CCR1, CCR5, and CCR8. Docking revealed high-affinity ligands interacting with residues GLU-9 and ACT-101, supporting the druggability of CCL18. Conclusions: Integrating single-cell analysis, pathway profiling, and docking highlights CCL18 as a promising therapeutic or vaccine target in PRAD. Its consistent tumor-immune expression and favorable binding properties support further experimental validation. Citation Format: Edwige Flore Gouegni, Gebre-Eziagbher Kiros, Renee Reams, Diana J. Wilke, Fredenburg Kristianna, Bodour Salhia. Integrative single-cell transcriptomics and computational docking identify CCL18 as an immunomodulatory target in prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4198.