Document Type
Article
Publication Date
9-3-2024
Abstract
OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).
METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.
RESULTS: Patients with advanced-stage, low K17 PDACs treated using 5-fluorouracil (5-FU)-based chemotherapeutic regimens had 3-fold longer survival than corresponding cases treated with gemcitabine-based chemotherapy. By contrast, PDACs with high K17 did not respond to either regimen. The predictive value of K17 was independent of tumor mutation status and other clinicopathologic variables.
CONCLUSIONS: The detection of K17 in 10% or greater of PDAC cells identified patients with shortest survival. Among patients with low K17 PDACs, 5-FU-based treatment was more likely than gemcitabine-based therapies to extend survival.
Recommended Citation
Delgado-Coka, Lyanne; Roa-Peña, Lucia; Babu, Sruthi; Horowitz, Michael; Petricoin, Emanuel; Matrisian, Lynn; Blais, Edik; Marchenko, Natalia; Allard, Felicia; Akalin, Ali; Jiang, MD, PhD, Wei; Larson, Brent; Hendifar, Andrew; Picozzi, Vincent; Choi, Minsig; Shroyer, Kenneth; and Escobar-Hoyos, Luisa, "Keratin 17 Is a Prognostic and Predictive Biomarker in Pancreatic Ductal Adenocarcinoma" (2024). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 423.
https://jdc.jefferson.edu/pacbfp/423
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
PubMed ID
38642081
Language
English
Comments
This article is the author's final published version in American Journal of Clinical Pathology, Volume 162, Issue 3, September 2024, Pages 314 - 326.
The published version is available at https://doi.org/10.1093/ajcp/aqae038.
Copyright © American Society for Clinical Pathology, 2024