In pancreatic ductal adenocarcinoma (PDAC), clinicians often ask whether young age is associated with more aggressive disease or patients more likely to tolerate curative-intent multimodality treatment. The prognostic meaning of age after surgery remains uncertain. We analyzed a retrospective multicenter surgical cohort of patients with resected non-metastatic PDAC. Candidate clinical variables were evaluated in univariable Cox models. The prespecified primary multivariable model included age, sex, N status, T stage, and CA19-9 status. Adjuvant therapy was evaluated in a sensitivity model. The cohort included 696 surgical patients; 70 (10.1%) were aged < 55 years. Median overall survival was 34.4 months in patients aged < 55 years versus 22.0 months in those aged ≥ 55 years (log-rank p = 0.019). In the primary multivariable model, age < 55 years remained independently favorable (HR 0.66, 95% CI 0.49–0.89; p = 0.007). Elevated CA19-9 value independently predicted worse survival (HR 1.39, 95% CI 1.13–1.71; p = 0.002). The sensitivity model confirmed favorable associations for young age and not elevated CA19-9 value. In surgically managed PDAC patients, young age and normal CA19-9 value carried independent favorable prognostic information. Prognosis was also shaped by nodal status, T stage, and receipt of adjuvant therapy.
I. Garajová, Bing-Zhi Wang, I. Chen et al.· Life· 0 citations
Pancreatic ductal adenocarcinoma remains a formidable clinical challenge, with a very poor survival rate. It is highly metastatic and quickly exhibits chemoresistance, both of which are mediated by interactions of the tumor cells with their microenvironment. Extracellular vesicles are key mediators by which tumor cells interact with their microenvironment. Here, we utilized a data-independent acquisition proteomics workflow to characterize the protein cargo of extracellular vesicles isolated from patient-derived primary cells and cell lines of varying aggressiveness. Mapping 1432 unique proteins with high reproducibility, we identified protein signatures that robustly discriminated between short-term and long-term survival phenotypes. While the data set was highly enriched for established exosomal markers, differential expression and PLS-DA modeling revealed that the most significant indicators of short survival (high aggressiveness) were ribosomal proteins. STRING analysis confirmed these as highly connected interactome hubs. These findings suggest that the differential loading of translational machinery into the extracellular space─likely via microvesicles or coisolated nonvesicular particles─contributes to poor prognosis, offering new insights into the systemic secretome of aggressive tumors.
Asia Botto, Noa Ndimurwanko, Francesco Finamore et al.· Journal of Proteome Research· 0 citations
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