Abstract
Purpose
Pancreatic Ductal Adenocarcinoma (PDAC) is the most common type of pancreatic malignancies. It is known for its aggressive nature and high mortality rate. This calls for an urgent need of new prognostic and therapeutic markers that can be targeted for personalized treatment of the patient.
Methods
Among 142 patients diagnosed with pancreatic cancers at Aga Khan University Hospital, a total of 62 patients were selected based on their confirmed diagnosis of PDAC. Immunohistochemistry was performed on Formalin-Fixed Paraffin-Embedded (FFPE) sections using selected antibodies (CD44, CD133, L1CAM, HER2, PD-L1, EGFR, COX2 and cyclin D1). All the slides were scored independently by two pathologists as per the set criteria.
Results
Expression of all cancer stem cell markers was found to be significantly associated with one or more potential therapeutic markers. CD44 expression was significantly associated with HER2 (p = 0.032), COX2 (p = 0.005) and EGFR expression (p = 0.008). CD133 expression also showed significant association with HER2 (p = 0.036), COX2 (p = 0.004) and EGFR expression (p = 0.018). L1CAM expression was found to be associated with expression of COX2 (p = 0.017). None of the proteins markers showed association with overall survival of the patient. On the other hand, among the clinicopathological characteristics, histological differentiation (p = 0.047), lymphovascular invasion (p = 0.021) and perineural invasion (p = 0.014) were found to be significantly associated with patient’s overall survival.
Conclusion
Internationally, this is the first report that assesses the selected panel of cancer stem cell markers and potential therapeutic targets in a single study and evaluates its combined expression. The study clearly demonstrates association between expression of cancer stem cell markers and therapeutic targets hence paves a way for precision medicine for pancreatic cancer patients.
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Data availability
Not Applicable.
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Funding
The study was funded by University Research Council (Grant ID: 183027SUR), Aga Khan University Hospital, Karachi, Pakistan.
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Research Idea: S.M Adnan Ali, Project Development and Proposal Writing for Grant—Yumna Adnan, Bench Work—Hasnain Ahmad Farooqui, Bench Work Supervision: S.M Adnan Ali, Review of H&E and Immunohistochemistry Slides—Zubair Ahmad, Patient Recruitment and Data Acquisition—Tabish Chawla, Data Entry—Saleema Mehboob Ali, Data Analysis and Interpretation—S.M Adnan Ali, Saleema Mehboob Ali and Yumna Adnan, Drafting of Manuscript—Saleema Mehboob Ali and S.M Adnan Ali, Critical Review and Manuscript Finalization—S.M Adnan Ali, Approval of Final Version of the Manuscript—All Authors.
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The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethical Review Committee of Aga Khan University Hospital, Karachi, Pakistan (2018-0449-1058).
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Ali, S.M.A., Adnan, Y., Ali, S.M. et al. Immunohistochemical analysis of a panel of cancer stem cell markers and potential therapeutic markers in pancreatic ductal adenocarcinoma. J Cancer Res Clin Oncol 149, 2279–2292 (2023). https://doi.org/10.1007/s00432-022-04315-4
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DOI: https://doi.org/10.1007/s00432-022-04315-4