Clinical and molecular characteristics of periampullary carcinoma based on pathological subtypes
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Periampullary carcinoma (PAC) is a relatively rare but highly aggressive malignancy, posing challenges to the determination of the optimal therapeutic approach. The objective of this study was to clarify the potential of histopathological typing in guiding chemotherapy selection for patients with advanced PAC and to characterize the distinct molecular features, underlying functional changes, and regulatory mechanisms associated with the different subtypes. Methods: We conducted a retrospective analysis of clinical data from patients with advanced PAC admitted to the Oncology Department of Xijing Hospital between January 2015 and May 2022. These patients received first-line chemotherapy with either FOLFOX (folinic acid, fluorouracil, and oxaliplatin) or gemcitabine-based regimens. Certain patients were divided into the pathological typing group and the control group. The pathological typing group received subtype-specific chemotherapy regimens, while the control group received chemotherapy regimens based on the primary tumor site. We compared the median progression-free survival (PFS) and overall survival (OS) between the two groups. Using publicly available databases (GSE60980), we conducted differential gene screening, enrichment analysis, and immune cell infiltration assessment. A protein-protein interaction (PPI) network was constructed based on the differentially expressed genes, resulting in the identification of 60 node genes. Subsequently, a core gene selection using the least absolute shrinkage and selection operator (LASSO) regression machine learning algorithm was performed to identify the key genes specific to PAC-PB subtype. Results: . 25.9 months; P=0.02). Multivariate Cox regression analysis revealed that pathological typing independently influenced PFS [hazard ratio (HR) =0.20, 95% confidence interval (CI): 0.10-0.44; P=0.009] and OS (HR =0.21, 95% CI: 0.17-0.71; P=0.02). Using a publicly available PAC cohort (GSE60980), we selected 154 differentially expressed genes, which were significantly enriched in signaling pathways related to the cell cycle, fibroblasts, and epithelial-mesenchymal transition. Analysis of immune cell infiltration indicated a significant increase in the abundance of fibroblast cells and a significant decrease in that of B cells and γδ T cells in the PAC-PB subtype. Furthermore, we identified core genes specific to the PAC-PB subtype and used them to construct a PAC-PB diagnostic model. Conclusions: Pathologic typing-guided individualized chemotherapy resulted in prolonged survival for patients with advanced PAC. The PB and IN subtypes of PAC exhibit distinct molecular regulatory mechanisms and immune infiltration microenvironments. These findings underscore the importance of considering subtype-specific factors in the development of a PAC-PB diagnostic model.
DOI: 10.21037/jgo-2025-14
Institutions: Xijing Hospital, Air Force Medical University, Tang Du Hospital
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4408008904