Intersection of Black race and carbohydrate antigen 19‐9 nonproduction underpins worse pathologic response to neoadjuvant therapy in pancreatic cancer
Year: 2025
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Black patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to have a major pathologic response (MPR) after neoadjuvant chemotherapy (NAC). Data suggest lower baseline carbohydrate antigen 19-9 (CA 19-9) among Black patients. Whether CA 19-9 nonproduction contributes to racial differences in NAC response was evaluated, and the biological mechanisms underlying the reduced response in CA 19-9 nonproducers (CAnonprod) were investigated. METHODS: Black and White patients with PDAC who received ≥2 NAC cycles and pancreatectomy at seven centers were reviewed. Patients were categorized as CA 19-9 producers (CAprod; CA 19-9 > 5 U/mL) or CAnonprod (CA 19-9 ≤ 5 U/mL). Univariable and multivariable models assessed CAnonprod rates by race and the association of CAnonprod with MPR. The Pancreatic Cancer Action Network's SPARK platform was queried for genomic data. Differentially mutated genes were identified by Fisher exact test; differentially expressed gene analysis used an absolute fold change of ≥2 and an adjusted p value of <.05. RESULTS: Among 415 patients (385 CAprod and 30 CAnonprod), Black patients comprised more CAnonprod than CAprod (50% vs. 13%; p < .01). MPR rates were lower among CAnonprod versus CAprod (8% vs. 26%; p = .03). CA nonproduction was associated with decreased odds of an MPR (odds ratio [OR], 0.21; 95% CI, 0.04-0.99), and Black race was associated with increased odds of CA 19-9 nonproduction (OR, 8.7; 95% CI, 3.8-19.7). CAnonprod had higher rates of SWI/SNF alterations than CAprod (52% vs. 34%; p < .01; p-adjusted, not significant). LIPF was downregulated and CTCFL was upregulated in CAnonprod. CONCLUSIONS: CA 19-9 nonproduction is more prevalent in Black patients, and potentially mediates lower rates of MPR. CAnonprod have a distinct molecular profile, which suggests a biological basis for racial differences in chemoresponsivity.
Source: Cancer
DOI: 10.1002/cncr.70130
Institutions: University of Miami, Sylvester Comprehensive Cancer Center, Pancreatic Cancer Action Network, University of Cincinnati, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Washington University in St. Louis, University of North Carolina at Chapel Hill, University of Wisconsin–Madison, Emory University, The University of Texas at San Antonio Health Science Center
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,790
Funders: Support for Pioneering Research Initiated by the Next Generation, Nepal Health Research Council, Government of Nepal, Knights Templar Eye Foundation, American Society of Hematology, International Retinal Research Foundation, Research to Prevent Blindness, Association for Frontotemporal Degeneration, Paul and Daisy Soros Fellowships for New Americans, Virginia and D.K. Ludwig Fund for Cancer Research, Naito Foundation, Takeda Science Foundation, North Carolina State University, Uehara Memorial Foundation, Montana Agricultural Experiment Station, Japan Agency for Medical Research and Development, Parker Institute for Cancer Immunotherapy, Chan Zuckerberg Initiative, Basis Foundation, National Institute of Technology Warangal, Biodiversa+, Morinaga Milk Industry, Instituto Nacional de Innovación Agraria, European Commission, National Research Foundation, Department of Science and Technology, Ministry of Science and Technology, India, Cure Kids, Deutsche Forschungsgemeinschaft, Danmarks Grundforskningsfond, Fundação de Amparo à Pesquisa do Estado de São Paulo, National Natural Science Foundation of China, Grantová Agentura České Republiky, ZonMw, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Austrian Science Fund, Soonchunhyang University, Universiti Tunku Abdul Rahman, Ferdowsi University of Mashhad, Fonds Wetenschappelijk Onderzoek, Euskal Herriko Unibertsitatea, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Korea Health Industry Development Institute, Türkiye Bilimsel ve Teknolojik Araştırma Kurumu, Natural Science Foundation of Hainan Province, Gauhati University, Foundation for Promotion of Cancer Research, Natural Science Foundation of Henan Province, Russian Science Foundation, Univerzita Palackého v Olomouci, National Forestry and Grassland Administration, Princess Takamatsu Cancer Research Fund, Ministry of Science and Higher Education of the Russian Federation, Nazarbayev University, Universidad Cooperativa de Colombia, Health Commission of Shandong Province, National Institutes of Health, Canadian Institutes of Health Research, Vanderbilt Vision Research Center, Vanderbilt University, Vanderbilt Diabetes Research and Training Center, Vanderbilt University Medical Center, Natural Sciences and Engineering Research Council of Canada, Arts and Humanities Research Council, Social Sciences and Humanities Research Council of Canada, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, Japan Society for the Promotion of Science, Eisai Incorporated, Chinese Universities Scientific Fund, Innovate UK, European Regional Development Fund, National Institute on Aging, National Eye Institute, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute of Environmental Health Sciences, Core Research for Evolutional Science and Technology, Science and Technology Department of Zhejiang Province, Fusion Oriented REsearch for disruptive Science and Technology, Exacte en Natuurwetenschappen
OpenAlex ID: W4415773853