AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility

Abstract Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo a...

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Main Authors: Mohamed Zardab, Barts Pancreas Tissue Bank, Richard P. Grose, Hemant M. Kocher
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87337-5
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author Mohamed Zardab
Barts Pancreas Tissue Bank
Richard P. Grose
Hemant M. Kocher
author_facet Mohamed Zardab
Barts Pancreas Tissue Bank
Richard P. Grose
Hemant M. Kocher
author_sort Mohamed Zardab
collection DOAJ
description Abstract Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker. At a plasma level of 421.47 ng/ml, AHNAK2 could potentially diagnose PDAC with a specificity and sensitivity of 83.33% and 86.67%. In vitro analysis suggests that in cell lines with diffuse cytoplasmic distribution of AHNAK2, there was colocalization of AHNAK2 with Cortactin in filipodia. This colocalization increased when cells were cultured on substrates such as Fibronectin and Collagen, as well as in hypoxia, and resulted in an augmented invasion of cancer cells. However, in cell lines with a vesicular AHNAK2 staining, such changes were not observed. Our study posits AHNAK2 as a valuable diagnostic biomarker in PDAC, now demanding prospective validation. Determination of mechanisms regulating AHNAK2 subcellular localisation may help explain its biological role.
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institution Kabale University
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spelling doaj-art-4e1ae28c17a94a3c94925f1b0c7772922025-01-26T12:32:08ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-87337-5AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motilityMohamed Zardab0Barts Pancreas Tissue BankRichard P. Grose1Hemant M. Kocher2Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of LondonCentre for Tumour Biology, Barts Cancer Institute, Queen Mary University of LondonCentre for Tumour Biology, Barts Cancer Institute, Queen Mary University of LondonAbstract Pancreatic ductal adenocarcinoma lacks suitable biomarkers for early diagnosis of disease. In gene panels developed for early diagnosis of pancreatic cancer, high AHNAK2 mRNA expression was one possible biomarker. In silico analysis of published human sample datasets (n = 177) and ex vivo analysis of human plasma samples (n = 30 PDAC with matched 30 healthy control) suggested AHNAK2 could be a diagnostic biomarker. At a plasma level of 421.47 ng/ml, AHNAK2 could potentially diagnose PDAC with a specificity and sensitivity of 83.33% and 86.67%. In vitro analysis suggests that in cell lines with diffuse cytoplasmic distribution of AHNAK2, there was colocalization of AHNAK2 with Cortactin in filipodia. This colocalization increased when cells were cultured on substrates such as Fibronectin and Collagen, as well as in hypoxia, and resulted in an augmented invasion of cancer cells. However, in cell lines with a vesicular AHNAK2 staining, such changes were not observed. Our study posits AHNAK2 as a valuable diagnostic biomarker in PDAC, now demanding prospective validation. Determination of mechanisms regulating AHNAK2 subcellular localisation may help explain its biological role.https://doi.org/10.1038/s41598-025-87337-5Pancreatic ductal adenocarcinomaOncogeneEzrinCortactinEarly diagnosis
spellingShingle Mohamed Zardab
Barts Pancreas Tissue Bank
Richard P. Grose
Hemant M. Kocher
AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
Scientific Reports
Pancreatic ductal adenocarcinoma
Oncogene
Ezrin
Cortactin
Early diagnosis
title AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
title_full AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
title_fullStr AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
title_full_unstemmed AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
title_short AHNAK2: a potential diagnostic biomarker for pancreatic cancer related to cellular motility
title_sort ahnak2 a potential diagnostic biomarker for pancreatic cancer related to cellular motility
topic Pancreatic ductal adenocarcinoma
Oncogene
Ezrin
Cortactin
Early diagnosis
url https://doi.org/10.1038/s41598-025-87337-5
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