Abstract
Abstract Introduction: Keratin 17 (K17) is a hallmark of the most aggressive molecular subtype of pancreatic ductal adenocarcinoma (PDAC). However, it is still unknown if K17 can predict the response to the two standard-of care treatments for PDAC: 1) 5-fluorouracil, irinotecan, leucovorin, and oxaliplatin (FFX) and 2) Gemcitabine/nab-paclitaxel (Gem/Nab). Thus, we hypothesized that K17 expression in patient tumors could be utilized as a biomarker to guide clinical decision-making in predicting the most effective standard-of-care treatment for patients with PDAC. Given that 85% of patients do not undergo resection, to circumvent this limitation we tested the predictive value of K17 using the tissue collected during endoscopic biopsies, which are routine in PDAC diagnosis. Methods: Our pilot study included 68 patients diagnosed with PDAC from Yale-New Haven Hospital treated with either FFX or Gem/Nab. Endoscopic biopsies were evaluated for tumor cellularity and then underwent an immunohistochemical (IHC)-based K17 test using the ABC detection method. Samples were scored by two independent pathologists using the PathSQ method. Results: Of the 68 patients included in the study, 20 (29.4%) were treated with Gem/Nab and 48 (70.6%) were treated with FFX. Based on Akaike’s Information Criterion, a K17 threshold of 45% and 60% were found to maximize stratification of patients by therapy response. At the 45% cutoff, 17 (25.0%) patients were found to have high K17 expression. At the 60% cutoff, 12 (17.6%) patients were found to have high K17 expression. Patients with low K17 expression were found to have similar overall survival (OS) despite treatment. However, patients with high K17 expression both at the 45% cutoff (p=0.031 and HR = 2.68 (CI 0.8, 8.99)) and 60% cutoff (p=0.006, HR = 6.79 (1.20, 38.32)) had decreased survival when treated with Gem/Nab compared to FFX. Conclusions: Patients with high K17 expression had lower overall survival than those with low K17 expression, validating our previous findings of K17 as a negative prognostic biomarker in PDAC. High K17 expression may be a promising predictive biomarker in PDAC, with an observed increase in OS in high K17-expressing patients treated with FFX compared to patients treated with Gem/Nab, indicating a potential biomarker to best determine response to standard-of-care treatments. Citation Format: Sumedha Chowdhury, Deanne Yugawa, Robert Tseng, Mauricio Mejia, Jill Lacy, Timil Patel, Luisa Escobar-Hoyos, Kenneth Shroyer, Guoping Cai, Marie Robert, Michael Cecchini, John Kunstman, James Farrell, Kimberly Johung. Keratin 17-signature for stratification of chemotherapy in pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A072.
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