Transcriptomic Profiling and Demographic Analysis of Appalachian Patients with Pancreatic Ductal Adenocarcinoma using the Purity Independent Subtyping of Tumors (PurIST) Classifier
- 1University of Kentucky
Abstract
PURPOSEPancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with poor prognosis. A transcriptomic-based algorithm called Purity Independent Subtyping of Tumors (PurIST) relies on expression profiling of a defined set of genes to stratify PDAC into classical and basal-like molecular subtypes and assigns a confidence level to the subtypes as either "strong," "likely," or "lean." In this study, we apply PurIST to Appalachian and non-Appalachian patient cohorts and assess demographic variables between groups that may influence treatment outcomes.
PATIENTS AND METHODSThis 13-site study includes 780 PDAC patients. Patients were divided into Appalachian and non-Appalachian cohorts according to Appalachian Regional Commission guidelines, and differences in PurIST classification, tobacco use, and alcohol use were analyzed.
RESULTSIndividuals from Appalachian regions were more likely to receive a subtype classification from PurIST with "strong" confidence as opposed to "likely" or "lean" (P=0.0175; odds ratio=1.66). We did not observe any significant difference between basal and classical subtype classification in Appalachia (P=0.1457), yet an exploratory analysis showed that individuals aged [≥]85 were significantly more likely to have basal-like tumor classifications (P=0.005817; odds ratio=3.79). Appalachian patients were more likely to have a history of smoking (59.6% vs 49.9%; P=0.01756) and less likely to report alcohol consumption (50.5% vs 65.6%; P=0.000229).
CONCLUSIONWe conducted the largest comparison of the PurIST algorithm in Appalachia to date and found PurIST is more likely to have higher confidence in molecular subtype classifications for Appalachian PDAC tumors compared to non-Appalachian tumors. If PurIST is to be considered as a prognostic or decision-making tool for PDAC patients, we must account for variability in different populations and model the likelihood that tumors will have a strong molecular signature.
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BibTeX
@misc{williams2026transcriptomic,
title = {{Transcriptomic Profiling and Demographic Analysis of Appalachian Patients with Pancreatic Ductal Adenocarcinoma using the Purity Independent Subtyping of Tumors (PurIST) Classifier}},
author = {C. M. Williams and R. A. Patel and N. A. Lisek and C. L. Kakarala and M. J. Cavnar and J. Kim and P. Pandalai and D. B. Allison and E. B. Toegel and T. Biachi and A. Manne and C. Chan and M. Rehman and D. Vadehra and D. W. Kim and M. Churchman and J. B. Miller},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.22.26363302},
url = {https://www.medrxiv.org/content/10.64898/2026.09.22.26363302v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Transcriptomic Profiling and Demographic Analysis of Appalachian Patients with Pancreatic Ductal Adenocarcinoma using the Purity Independent Subtyping of Tumors (PurIST) Classifier
AU - C. M. Williams
AU - R. A. Patel
AU - N. A. Lisek
AU - C. L. Kakarala
AU - M. J. Cavnar
AU - J. Kim
AU - P. Pandalai
AU - D. B. Allison
AU - E. B. Toegel
AU - T. Biachi
AU - A. Manne
AU - C. Chan
AU - M. Rehman
AU - D. Vadehra
AU - D. W. Kim
AU - M. Churchman
AU - J. B. Miller
PY - 2026
DA - 2026/09/22
PB - medRxiv
DO - 10.64898/2026.09.22.26363302
UR - https://www.medrxiv.org/content/10.64898/2026.09.22.26363302v1
AB - PURPOSEPancreatic ductal adenocarcinoma (PDAC) is a deadly malignancy with poor prognosis. A transcriptomic-based algorithm called Purity Independent Subtyping of Tumors (PurIST) relies on expression profiling of a defined set of genes to stratify PDAC into classical and basal-like molecular subtypes and assigns a confidence level to the subtypes as either "strong," "likely," or "lean." In this study, we apply PurIST to Appalachian and non-Appalachian patient cohorts and assess demographic variables between groups that may influence treatment outcomes. PATIENTS AND METHODSThis 13-site study includes 780 PDAC patients. Patients were divided into Appalachian and non-Appalachian cohorts according to Appalachian Regional Commission guidelines, and differences in PurIST classification, tobacco use, and alcohol use were analyzed. RESULTSIndividuals from Appalachian regions were more likely to receive a subtype classification from PurIST with "strong" confidence as opposed to "likely" or "lean" (P=0.0175; odds ratio=1.66). We did not observe any significant difference between basal and classical subtype classification in Appalachia (P=0.1457), yet an exploratory analysis showed that individuals aged [≥]85 were significantly more likely to have basal-like tumor classifications (P=0.005817; odds ratio=3.79). Appalachian patients were more likely to have a history of smoking (59.6% vs 49.9%; P=0.01756) and less likely to report alcohol consumption (50.5% vs 65.6%; P=0.000229). CONCLUSIONWe conducted the largest comparison of the PurIST algorithm in Appalachia to date and found PurIST is more likely to have higher confidence in molecular subtype classifications for Appalachian PDAC tumors compared to non-Appalachian tumors. If PurIST is to be considered as a prognostic or decision-making tool for PDAC patients, we must account for variability in different populations and model the likelihood that tumors will have a strong molecular signature.
ER -