Pan-Cancer Analysis Identifies LUC7L2 as a Prognostic Biomarker and Potential Functional Regulator of Prostate Cancer Progression

Background/Objectives: Cancer imposes a substantial global public health burden, and its initiation and progression involve complex dysregulation of gene expression regulatory networks. Methods: This study systematically evaluated the expression characteristics and prognostic value of LUC7L2 across pan-cancer types, with a particular focus on functional validation in prostate cancer. Using transcriptomic and proteomic data from multiple databases, immunohistochemical staining from the Human Protein Atlas, and single-cell transcriptomic datasets GSE137829 and GSE176031, we analyzed the expression patterns of LUC7L2 in various cancer types. Diagnostic and prognostic potential was assessed through ROC curve analysis, Cox regression, single-cell, and spatial transcriptomics, while the functional role of LUC7L2 in prostate cancer tumorigenesis and progression was validated via in vitro assays. Results: Results showed that LUC7L2 was significantly upregulated in glioblastoma and prostate adenocarcinoma, and downregulated in lung adenocarcinoma and ovarian serous cystadenocarcinoma, with diagnostic AUC values exceeding 0.7 across multiple tumor types. In prostate cancer, high LUC7L2 expression was significantly associated with a shortened progression-free interval (multivariate HR = 3.50, 95% CI 1.95–6.29, p < 0.001), with a meta-analysis of independent cohorts showing a consistent direction of effect (pooled HR = 1.14, 95% CI 0.90–1.44). Moreover, LUC7L2 exhibited strong correlations with microsatellite instability and tumor mutational burden across multiple cancer types. Single-cell analysis revealed that its expression was markedly higher in malignant cells than in immune or stromal cells. In vitro knockdown of LUC7L2 in prostate cancer cells led to significantly suppressed proliferation, increased apoptosis, S-phase cell cycle arrest, reduced invasion and migration capacities, enhanced senescence, and aggravated DNA damage. Conclusions: This study demonstrates that LUC7L2 is specifically overexpressed in malignant prostate cancer cells and independently associated with poor prognosis. It further validates its regulatory roles in proliferation, apoptosis, migration, and DNA damage repair, providing both theoretical and experimental evidence supporting LUC7L2 as a potential biomarker for prostate cancer.