Multiomics, pharmacogenomic, and structural characterization of NCCRP1 as a candidate therapeutic target in ovarian...

Ovarian cancer is characterized by extensive molecular heterogeneity and poor clinical outcomes, highlighting the need to identify biologically relevant therapeutic targets. NCCRP1 remains poorly characterized in ovarian cancer, and its molecular and therapeutic significance is largely unknown. In this study, we applied an integrative multiomics framework incorporating transcriptomic profiling, survival analysis, immune microenvironment characterization, pathway and network analyses, pharmacogenomic assessment, structural modeling, and single-cell RNA sequencing to investigate the role of NCCRP1 in ovarian cancer. Family-wide screening of the TCGA-OV cohort identified NCCRP1 as the only member significantly associated with overall survival. Elevated NCCRP1 expression was enriched in tumor tissues and associated with adverse clinical outcomes. Functional analyses demonstrated that NCCRP1-high tumors exhibit activation of epithelial-mesenchymal transition, cytoskeletal remodeling, adhesion signaling, and hypoxia-associated pathways, suggesting involvement in tumor plasticity and progression. Network-based analyses further positioned NCCRP1 within regulatory programs linked to structural reorganization and aggressive tumor phenotypes. Single-cell RNA sequencing confirmed that NCCRP1 expression is predominantly localized to malignant epithelial populations, supporting a tumor-intrinsic role. Pharmacogenomic analyses identified NCCRP1-associated transcriptional states linked to distinct drug sensitivity patterns, while structural modeling suggested the presence of a surface-accessible cavity capable of accommodating small molecules. Although these findings require experimental validation, they provide preliminary evidence supporting the potential druggability of NCCRP1. Our findings provide a comprehensive molecular characterization of NCCRP1 and support its prioritization as a candidate therapeutic target in ovarian cancer. This study demonstrates the utility of integrating multiomics, pharmacogenomic, structural, and single-cell approaches for therapeutic target discovery and prioritization in cancer.