Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data

Abstract Pancreatic cancer (PC) is a highly aggressive and fatal malignancy, primarily affecting older males. Curcumin, a potential anti-cancer agent, has been shown to regulate key molecules in cancer progression, but its specific mechanisms in PC remain unclear. We conducted a comprehensive databa...

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Main Authors: HongMing Xie, JieBin Liang, HongBiao He, Zewei Zhuo, JiaXuan Li
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-05346-w
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author HongMing Xie
JieBin Liang
HongBiao He
Zewei Zhuo
JiaXuan Li
author_facet HongMing Xie
JieBin Liang
HongBiao He
Zewei Zhuo
JiaXuan Li
author_sort HongMing Xie
collection DOAJ
description Abstract Pancreatic cancer (PC) is a highly aggressive and fatal malignancy, primarily affecting older males. Curcumin, a potential anti-cancer agent, has been shown to regulate key molecules in cancer progression, but its specific mechanisms in PC remain unclear. We conducted a comprehensive database search to identify curcumin-related targets in PC. Gene expression and immune correlations were analyzed using the GEO database, identifying differentially expressed hub genes (DEHGs). A method involving machine learning was employed to identify feature genes and create a nomogram, using external datasets and molecular docking for preliminary validation. Consensus clustering and subgroup comparisons were also performed based on DEHGs expression. We identified 35 DEHGs strongly associated with immune cell infiltration. Five feature genes (VIM, CTNNB1, CASP9, AREG, HIF1A) were used to build a nomogram, with the classification model showing AUC values above 0.9 in both training and validation groups. Molecular docking highlighted potential binding sites of five feature genes for curcumin. Clustering analysis categorized PC samples into four distinct subgroups: C1 and CII, which showed high expression and elevated immune cell infiltration, and C2 and CI, which exhibited the opposite pattern. Significant variations in scores of DEHG were seen between C1 and C2, in addition to between CI and CII. Curcumin may target DEHGs to influence PC, regulating immune and tumor proliferation mechanisms. These outcomes provide potential insights for medical applications and upcoming research.
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spelling doaj-art-50a22aec8de04b23a9b38818ed2dce012025-08-20T03:03:42ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-05346-wUnveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional dataHongMing Xie0JieBin Liang1HongBiao He2Zewei Zhuo3JiaXuan Li4Department of Gastroenterology, Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western MedicineDepartment of Gastroenterology, Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western MedicineDepartment of Gastroenterology, Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western MedicineDepartment of Gastroenterology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Southern Medical UniversityDepartment of Gastroenterology, Zhongshan Chenxinghai Hospital of Integrated Traditional Chinese and Western MedicineAbstract Pancreatic cancer (PC) is a highly aggressive and fatal malignancy, primarily affecting older males. Curcumin, a potential anti-cancer agent, has been shown to regulate key molecules in cancer progression, but its specific mechanisms in PC remain unclear. We conducted a comprehensive database search to identify curcumin-related targets in PC. Gene expression and immune correlations were analyzed using the GEO database, identifying differentially expressed hub genes (DEHGs). A method involving machine learning was employed to identify feature genes and create a nomogram, using external datasets and molecular docking for preliminary validation. Consensus clustering and subgroup comparisons were also performed based on DEHGs expression. We identified 35 DEHGs strongly associated with immune cell infiltration. Five feature genes (VIM, CTNNB1, CASP9, AREG, HIF1A) were used to build a nomogram, with the classification model showing AUC values above 0.9 in both training and validation groups. Molecular docking highlighted potential binding sites of five feature genes for curcumin. Clustering analysis categorized PC samples into four distinct subgroups: C1 and CII, which showed high expression and elevated immune cell infiltration, and C2 and CI, which exhibited the opposite pattern. Significant variations in scores of DEHG were seen between C1 and C2, in addition to between CI and CII. Curcumin may target DEHGs to influence PC, regulating immune and tumor proliferation mechanisms. These outcomes provide potential insights for medical applications and upcoming research.https://doi.org/10.1038/s41598-025-05346-wCurcuminPancreatic cancerMachine learningNomogramNetwork pharmacology
spellingShingle HongMing Xie
JieBin Liang
HongBiao He
Zewei Zhuo
JiaXuan Li
Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
Scientific Reports
Curcumin
Pancreatic cancer
Machine learning
Nomogram
Network pharmacology
title Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
title_full Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
title_fullStr Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
title_full_unstemmed Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
title_short Unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi-dimensional data
title_sort unveiling the mechanisms and promising molecular targets of curcumin in pancreatic cancer through multi dimensional data
topic Curcumin
Pancreatic cancer
Machine learning
Nomogram
Network pharmacology
url https://doi.org/10.1038/s41598-025-05346-w
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