Abstract
BACKGROUND: Among all solid tumors, pancreatic ductal adenocarcinoma (PDAC) is characterized by markedly poor survival outcomes, reflecting its high lethality, primarily as a result of late-stage diagnosis and limited treatment options. Pancreatic adenocarcinoma upregulated factor (PAUF) displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development. However, its exact diagnostic and prognostic significance remains unclear. This study aimed to assess the clinical relevance of PAUF expression in PDAC. We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes. AIM: To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker. METHODS: PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC. Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups. Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed. Public datasets (The Cancer Genome Atlas, Genotype-Tissue Expression, and Clinical Proteomic Tumor Analysis Consortium) were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels. RESULTS: PAUF expression was observed in 82.8% of samples, primarily localized within the cytoplasm of tumor cells. High PAUF expression showed a significant correlation with metastasis to lymph nodes (78.4%, P = 0.0019), indicating a strong association with advanced disease. Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue. Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival (18.4 months vs 32.7 months, P = 0.032). Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes [hazard ratio (HR) = 2.05; P = 0.009]. Poor tumor differentiation (HR = 2.47; P = 0.004) and lack of adjuvant therapy (HR = 0.39; P = 0.001) were also independently associated with unfavorable outcomes. CONCLUSION: PAUF is a promising biomarker for tumor progression and prognosis in PDAC, with potential clinical utility in early diagnosis and the development of targeted therapies.