KAZALD1 upregulation predicts poor prognosis in epithelial ovarian cancer: Clinical validation and immune correlates

Reliable biomarkers for accurate risk stratification in epithelial ovarian cancer (EOC) remain limited. While kazal type serine peptidase inhibitor domain 1 (KAZALD1), a secreted proteoglycan, has been implicated in numerous tumors, its clinical value in EOC remains unknown. The present study evaluated whether KAZALD1 is an independent prognostic biomarker in EOC and explored its associations with immune‑cell infiltration and tumor microenvironment‑associated pathways. KAZALD1 expression was analyzed using Gene Expression Omnibus datasets (GSE66957 and GSE140082) and validated through immunohistochemical (IHC) analysis in 136 EOC samples. The Cancer Genome Atlas‑Ovarian Cancer cohort (n=307) was utilized to explore immune infiltration and functional pathways. KAZALD1 mRNA levels were found to be significantly elevated in ovarian cancer compared with non‑carcinoma tissues (adjusted P<0.001). In GSE140082, KAZALD1 upregulation correlated with poor overall survival (OS) and progression‑free survival. IHC analysis determined that high KAZALD1 protein expression was significantly associated with distant metastasis (P=0.002) and advanced International Federation of Gynecology and Obstetrics stage (P=0.011). Patients with high KAZALD1 expression exhibited a significantly shorter median OS (45.0 vs. 77.0 months; P=0.015). Multivariate Cox regression identified KAZALD1 as an independent prognostic factor (hazard ratio: 1.09; 95% CI: 1.00‑1.19; P=0.042). Exploratory bioinformatic analysis demonstrated that KAZALD1 expression inversely correlated with the estimated abundance of macrophage (r=‑0.431; P=0.020) and dendritic cell (r=‑0.486; P=0.008) infiltration. In addition, its co‑expression network was significantly enriched in TGF‑β and extracellular matrix organization pathways. In conclusion, KAZALD1 was found to be a candidate independent prognostic biomarker for EOC. The observed immune associations are correlative and require validation in functional studies, spatially resolved analyses, prospective cohorts and immunotherapy‑treated populations.