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Peer-reviewedCC BY-NC-ND 4.0Oncology Letters

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

  • Ruru Zhao1
  • Ye Hu2
  • Jia Wang3
  • Jingjing Lu3
  • Guiqiang Du1
  1. 1Department of Obstetrics and Gynecology, Shanghai First Maternity and Infant Hospital, Obstetrics and Gynecology Hospital of Tongji University, Shanghai 201204, P.R. China
  2. 2Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China
  3. 3Department of Obstetrics and Gynecology, Hainan Hospital of Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Sanya, Hainan 572000, P.R. China
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026kazald1,
  title = {{KAZALD1 upregulation predicts poor prognosis in epithelial ovarian cancer: Clinical validation and immune correlates}},
  author = {Ruru Zhao and Ye Hu and Jia Wang and Jingjing Lu and Guiqiang Du},
  journal = {Oncology Letters},
  year = {2026},
  month = oct,
  doi = {10.3892/ol.2026.15908},
  url = {https://doi.org/10.3892/ol.2026.15908},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - KAZALD1 upregulation predicts poor prognosis in epithelial ovarian cancer: Clinical validation and immune correlates
AU  - Ruru Zhao
AU  - Ye Hu
AU  - Jia Wang
AU  - Jingjing Lu
AU  - Guiqiang Du
PY  - 2026
DA  - 2026/10/15
JO  - Oncology Letters
DO  - 10.3892/ol.2026.15908
UR  - https://doi.org/10.3892/ol.2026.15908
AB  - 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.
SN  - 1792-1074
SN  - 1792-1082
ER  -