1. Keratin 17 is a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma.
- Author
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Delgado-Coka LA, Roa-Peña L, Babu S, Horowitz M, Petricoin EF 3rd, Matrisian LM, Blais EM, Marchenko N, Allard FD, Akalin A, Jiang W, Larson BK, Hendifar AE, Picozzi VJ, Choi M, Shroyer KR, and Escobar-Hoyos LF
- Subjects
- Humans, Male, Female, Prognosis, Middle Aged, Aged, Fluorouracil therapeutic use, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Gemcitabine, Immunohistochemistry, Adult, Aged, 80 and over, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal diagnosis, Pancreatic Neoplasms pathology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms mortality, Pancreatic Neoplasms genetics, Pancreatic Neoplasms diagnosis, Biomarkers, Tumor metabolism, Keratin-17 metabolism, Keratin-17 genetics
- 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., (© American Society for Clinical Pathology, 2024.)
- Published
- 2024
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