Kim JH, Na HY, Jung K, Jang D, Youn Y, Kim DH, Han HD, Hwang JH. Quantitative immunohistochemistry analysis of pancreatic adenocarcinoma upregulated factor expression in pancreatic cancer and its prognostic significance. World J Gastrointest Oncol 2025; 17(9): 109055 [DOI: 10.4251/wjgo.v17.i9.109055]
Corresponding Author of This Article
Jin-Hyeok Hwang, MD, PhD, Professor, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Seongnam-si 13620, Gyeonggi-do, South Korea. jhhwang@snubh.org
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastrointest Oncol. Sep 15, 2025; 17(9): 109055 Published online Sep 15, 2025. doi: 10.4251/wjgo.v17.i9.109055
Quantitative immunohistochemistry analysis of pancreatic adenocarcinoma upregulated factor expression in pancreatic cancer and its prognostic significance
Jae Hyeong Kim, Hee Young Na, Kwangrok Jung, Dayeon Jang, Yuna Youn, Dae Hwan Kim, Hee Dong Han, Jin-Hyeok Hwang
Jae Hyeong Kim, Kwangrok Jung, Dayeon Jang, Yuna Youn, Jin-Hyeok Hwang, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam-si 13620, Gyeonggi-do, South Korea
Hee Young Na, Department of Pathology, Seoul National University Bundang Hospital, Seongnam-si 13620, Gyeonggi-do, South Korea
Hee Young Na, Department of Pathology and Translational Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea
Dae Hwan Kim, Hee Dong Han, Prestige Biopharma Innovative Discovery Centre, Busan 46726, South Korea
Jin-Hyeok Hwang, Department of Internal Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea
Co-first authors: Jae Hyeong Kim and Hee Young Na.
Author contributions: Kim JH and Na HY contributed equally to this work and are considered co-first authors; Kim JH designed the study, acquired the data, performed statistical analysis, and drafted the manuscript; Na HY performed immunohistochemistry staining, interpreted pathological data, and contributed to data analysis; Jung K, Jang D, and Youn Y participated in sample collection, experimental procedures, and data curation; Kim DH and Han HD contributed to clinical data interpretation and critical review of the manuscript; Hwang JH conceptualized and supervised the study, secured funding, and revised and finalized the manuscript. All authors read and approved the final manuscript.
Supported by Seoul National University Bundang Hospital Research Fund, No. 06-2021-0140; and National Research Foundation of Korea, No. RS-2024-00335454.
Institutional review board statement: This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital, No. B-2103-675-106.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study are available on request from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin-Hyeok Hwang, MD, PhD, Professor, Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173 Beon-gil, Seongnam-si 13620, Gyeonggi-do, South Korea. jhhwang@snubh.org
Received: May 9, 2025 Revised: July 4, 2025 Accepted: August 4, 2025 Published online: September 15, 2025 Processing time: 138 Days and 0.9 Hours
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.
Core Tip: This study reveals that pancreatic adenocarcinoma upregulated factor is overexpressed in pancreatic ductal adenocarcinoma and displays a significant relationship with metastasis to lymph nodes. High pancreatic adenocarcinoma upregulated factor expression correlates with shorter overall survival and independently predicts poor prognosis, supporting its role as a biomarker for patient stratification and targeted therapy development.
