Genetic Variants and Soluble Isoforms of PD-1/PD-L1 as Novel Biomarkers for Pancreatic Ductal Adenocarcinoma (PDAC) Susceptibility and Prognosis

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Hassan M.; El-Maadawy W.H.; Elhusseny Y.; Agamy F.E.; Fahim S.A.; Balata M.

Journal: Biomedicines

Publisher: Multidisciplinary Digital Publishing Institute (MDPI)

Publication Date: 12 September 2025

Volume / Issue: Volume 13 / Issue 9

Article No.: 2246

ISSN: 22279059

DOI: 10.3390/biomedicines13092246

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

Hassan M., Immunology Department, Theodor Bilharz Research Institute, Giza, 12411, Egypt; El-Maadawy W.H., Pharmacology Department, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Elhusseny Y., Medical Biochemistry and Molecular Biology Department, School of Medicine, NewGiza University, Giza, 12585, Egypt; Agamy F.E., Faculty of Medicine, Al-Azhar University, Cairo, 11884, Egypt; Fahim S.A., Biochemistry Department, School of Pharmacy, NewGiza University, Giza, 94114, Egypt; Balata M., University Hospital Bonn, Venusberg-Campus 1, Bonn, 53127, Germany, University Hospital Rostock, Ernst-Heydemann-Straße 6, Rostock, 18057, Germany

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm often diagnosed at advanced stages. Immune checkpoint molecules, particularly programmed cell death protein-1 (PD-1) and its ligand PD-L1, are pivotal in tumor immune evasion. Genetic polymorphisms in PD-1/PD-L1 and their soluble isoforms (sPD-1/sPD-L1) may influence individual susceptibility to cancer and disease progression. Therefore, this study was conducted to examine the correlation between PD-1/PD-L1 gene polymorphisms, serum levels of sPD-1/sPD-L1, and their association with PDAC susceptibility, severity, and prognostication. Methods: This case–control study was performed with 150 PDAC patients and 150 controls. Clinical and laboratory data, including tumor markers (CA19-9 and CEA), were recorded. Allele-specific PCR was utilized to genotype PD-1 (rs6749527 and rs7421861) and PD-L1 (rs2297136, and rs4143815). sPD-1/sPD-L1 were quantified with ELISA. Mapping of the Kaplan–Meier survival curve of mutant genes was performed. Results: The rs7421861 AG and GG and rs4143815 GG genotypes, together with their G-alleles, were linked to increased PDAC risk and greater tumor burden. In contrast, the rs2297136 GG genotype and G-allele conferred protection against PDAC development. Serum sPD-L1 levels, rather than sPD-1, were markedly elevated in PDAC patients, progressively increased with tumor grade, and correlated with tumor markers. Also, higher PD-L1 gene expression was associated with lower overall survival. Conclusions: PD-1/PD-L1 genetic variants, particularly rs7421861 and rs4143815, along with sPD-L1 levels, correlate with PDAC susceptibility and disease severity. These findings endorse the prospects of integrating immune checkpoint genetic variants and soluble biomarkers for early identification, risk stratification, prognostication, and personalized therapeutic strategies in PDAC management. © 2025 by the authors.

Keywords

immune checkpoint; pancreatic ductal adenocarcinoma; PD-1; PD-L1; rs4143815; rs7421861; single nucleotide polymorphism; alanine aminotransferase; albumin; aspartate aminotransferase; bilirubin; biological marker; creatinine; genomic DNA; immune checkpoint inhibitor; immune checkpoint protein; programmed death 1 ligand 1; programmed death 1 receptor; tumor necrosis factor; urea; adult; allele; Article; blood sampling; cancer chemotherapy; cancer immunotherapy; cancer patient; cancer prognosis; cancer radiotherapy; cancer staging; cancer susceptibility; case control study; CD8+ T lymphocyte; cell death; clinical outcome; cohort analysis; computer assisted tomography; controlled study; female; genetic polymorphism; genetic variability; genotype; human; immune evasion; immune response; major clinical study; male; middle aged; nuclear magnetic resonance imaging; overall survival; pancreas cancer; pancreatic ductal carcinoma; protein protein interaction; smoking

Citation Information

Scopus Citations: 5

For comprehensive information about the Theodor Bilharz Research Institute (TBRI), its institutional activities, scientific and research achievements, clinical and hospital services, and the diverse expertise offered through its 22 specialized research and clinical departments, as well as opportunities for professional training, specialized workshops, and scientific conferences, readers are invited to visit the Institute’s official website.

The website provides regularly updated information on the Institute’s latest news, research activities, scientific initiatives, clinical services, institutional programs, and academic and professional opportunities.

English Website: https://www.tbri.sci.eg/en/

Arabic Website: https://www.tbri.sci.eg/ar/

Prepared and Uploaded by:

Abdalla F. Abdalla

Electronic Portal Unit

Electronic Portal Unit

Popular Posts

A cost-performance index for nano-optical biosensor evaluation: Systematic evaluation of europium–salicylate luminescent platforms for GPC3-targeted early HCC diagnosis

Image
Bibliographic Information Authors: Hassan Y.M.; El-Tantawi H.; Ali I.R.; Attia M.S. Journal: Talanta Publisher: Elsevier B.V. Publication Date: January 2027 Volume / Issue: Volume 311 Article No.: 130103 ISSN: 399140 DOI: 10.1016/j.talanta.2026.130103 Scopus: View on Scopus PubMed: 42391698 Document Type: Review Authors and Affiliations Hassan Y.M., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; El-Tantawi H., Department of Zoology, Faculty of Science, Ain Shams University, Abbassia, Cairo, 11566, Egypt; Ali I.R., Department of Immunology and Treatment Evaluation, Theodore Bilharz Research Institute, Giza, Egypt; Attia M.S., Chemistry Department, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, 11623, Saudi Arabia Abstract Comparative evaluation of nano-optical biosensor platforms lacks a standardised, multi-parameter quantitative framework that integrates analytical performance...
Read more

Interpretation of liver stiffness measurement in patients with mixed liver disease etiologies

Image
Bibliographic Information Authors: El Ray A.; El Ghannam M.; Rautou P.E. Journal: Arab Journal of Gastroenterology Publisher: Elsevier Ltd Publication Date: August 2026 ISSN: 16871979 DOI: 10.1016/j.ajg.2026.05.002 Scopus: View on Scopus PubMed: 42362465 Document Type: Letter Authors and Affiliations El Ray A., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt, Faculty of Medicine, October 6 University, Egypt; El Ghannam M., Theodor Bilharz Research Institute, Hepatogastroenterology Department, Giza, Egypt; Rautou P.E., Université Paris-Cité, Inserm, Centre de recherche sur l’inflammation, UMR 1149, Paris, France, AP-HP, Hôpital Beaujon, Service d’Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Clichy, France Abstract Vibration-controlled transient elastography (VCTE)–based liver stiffness measurement (LSM) is widely used for non-invasive assessment of liver fibrosis and p...
Read more

Multifunctional polycaprolactone-based composite fibers with icariin and glutathione for effective repair of critical-sized bone defects

Image
Bibliographic Information Authors: Yessuf A.M.; Zhang Y.; Sharma B.P.; Wang Y.; Kassa T.S.; Qadir A.; Jinqiu Y.; Mohideen M.M.; Salama A.M.; Wang W.; Zhang Q.; Liu Y. Journal: BMEMat Publisher: John Wiley and Sons Inc Publication Date: 30 July 2026 ISSN: 27517438 DOI: 10.1002/bmm2.70115 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access Authors and Affiliations Yessuf A.M., Key Laboratory of Advanced Functional Polymer Composites, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Zhang Y., Henan Provincial Orthopedic Hospital, Henan, Zhengzhou, China; Sharma B.P., Key Laboratory of Electrochemical Process and Technology of Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing, China; Wang Y., Beijing University of Chinese Medicine, Beijing, China; Kassa T.S., Key Laboratory of Advanced Functional Polymer Composites, Col...
Read more

Holothuria arenicola Extract-Loaded Polycaprolactone Nanocapsules Attenuate Bile Duct Ligation-Induced Acute Liver Injury

Image
Bibliographic Information Authors: Mansour E.M.; Shemis M.; Fahmy S.R.; Amer M.A.; Mohamed A.S. Journal: Current Nanomedicine Publisher: Bentham Science Publishers Publication Date: September 2026 Volume / Issue: Volume 16 / Issue 5 Pages: 771–786 ISSN: 24681873 DOI: 10.2174/0124681873401484250924125945 Scopus: View on Scopus Document Type: Article Authors and Affiliations Mansour E.M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Shemis M., Department of Biochemistry and Molecular Biology, Theodor Bilharz Research Institute, Giza, Egypt; Fahmy S.R., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Amer M.A., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt; Mohamed A.S., Department of Zoology, Faculty of Science, Cairo University, Giza, Egypt Abstract Introduction: Cholestatic liver diseases are characterized by jaundice and cholestasis with various conseq...
Read more

Mytilus edulis-mediated green synthesis of selenium nanoparticles with antimicrobial and molluscicidal applications

Image
Bibliographic Information Authors: Dokmak H.-A.A.; AlSedawy M.; Ramadan M.A.; Amin B.H.; Faid A.H.; Abdelmaksoud H.F.; El-Sayed S.M. Journal: Scientific Reports Publisher: Nature Research Publication Date: 7 September 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 27918 ISSN: 20452322 DOI: 10.1038/s41598-026-65860-3 Scopus: View on Scopus PubMed: 42706305 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Dokmak H.-A.A., Department of Medical Malacology, Theodor Bilharz Research Institute, Giza, Egypt; AlSedawy M., Microbiology and Immunology Department, Faculty of Pharmacy (For Boys), Al-Azhar University, Cairo, Egypt; Ramadan M.A., Department of Laser Application in Metrology, Photochemistry and Agriculture, National Institute of Laser Enhanced Science (NILES) Cairo University (CU), Giza, Egypt; Amin B.H., The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, 11787,...
Read more

Microbial levan potentiates hepatic retention and antitumor activity of a PEGylated benzimidazole–curcumin nanocomplex through TLR2–FXR/FGF15-associated immunometabolic remodeling in experimental liver cancer

Image
Bibliographic Information Authors: Shawky H.; Ibrahim N.E.; Amer M.N.; Al-Ashmawy A.A.K.; Hammam O.A.; Fayed D.B.; Maghraby A.S. Journal: Scientific Reports Publisher: Nature Research Publication Date: 12 August 2026 Volume / Issue: Volume 16 / Issue 1 Article No.: 25094 ISSN: 20452322 DOI: 10.1038/s41598-026-64576-8 Scopus: View on Scopus PubMed: 42581056 Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Shawky H., Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Ibrahim N.E., Microbial Biotechnology Department, Biotechnology Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Amer M.N., Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12622, Egypt; Al-Ashmawy A.A.K., Therapeutic Chem...
Read more

Variable clinical presentations of pulmonary hydatid cysts: a four-case series from a single center in United Arab Emirates, non-endemic region

Image
Bibliographic Information Authors: Yehya M.; Abdallah M.F.H.; Ajeka S.; Al-Masalmeh F.H.; Albaghdadi M.O.J. Journal: Journal of Surgical Case Reports Publisher: Oxford University Press Publication Date: 29 July 2026 Volume / Issue: Volume 2026 / Issue 7 Article No.: rjag658 ISSN: 20428812 DOI: 10.1093/jscr/rjag658 Scopus: View on Scopus Document Type: Article Access: All Open Access; Gold Open Access; Green Open Access Authors and Affiliations Yehya M., Department of Thoracic Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Abdallah M.F.H., Department of Radiology, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates, Theodor Bilharz Research Institute, Mahad Al Abhas Al bahari St, Kornish Al Nile, Warraq Al Arab, Al Warak, Governorate, Giza, 3863341, Egypt; Ajeka S., Department of General Surgery, SAQR Hospital, Al Juwais Al Kadi St, Ras Al-Khaimah, United Arab Emirates; Al-Masalmeh F.H., Department of ...
Read more