Female-specific pancreatic cancer survival from CT imaging of visceral fat implicates glutathione metabolism in solid tumors.

Autor:	Ballard DH; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (D.H.B., G.K.N., S.J., D.R.L., V.M.M., J.E.I.)., Nguyen GK; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (D.H.B., G.K.N., S.J., D.R.L., V.M.M., J.E.I.)., Atagu N; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland (N.A.)., Camps G; Washington University School of Medicine, Washington University School of Medicine, St. Louis, MO (G.C.)., Salter A; Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, TX (A.S.)., Jaswal S; Department of Radiology, Weill Cornell Medical Center/New York Presbyterian Hopsital, New York, NY (S.J.)., Naeem M; Department of Radiology, Emory University School of Medicine, Atlanta, GA (M.N.)., Ludwig DR; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (D.H.B., G.K.N., S.J., D.R.L., V.M.M., J.E.I.)., Mellnick VM; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (D.H.B., G.K.N., S.J., D.R.L., V.M.M., J.E.I.)., Peterson LR; Department of Medicine, Washington University School of Medicine, St. Louis, MO (L.R.P.)., Hawkins WG; Department of Surgery, Washington University School of Medicine, St. Louis, MO (W.G.H., R.C.F.)., Fields RC; Department of Surgery, Washington University School of Medicine, St. Louis, MO (W.G.H., R.C.F.)., Luo J; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, MO (J.L.)., Ippolito JE; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO (D.H.B., G.K.N., S.J., D.R.L., V.M.M., J.E.I.). Electronic address: ippolitoj@wustl.edu.
Jazyk:	angličtina
Zdroj:	Academic radiology [Acad Radiol] 2024 Jun; Vol. 31 (6), pp. 2312-2323. Date of Electronic Publication: 2023 Dec 20.
DOI:	10.1016/j.acra.2023.11.012
Abstrakt:	Rationale and Objectives: To identify if body composition, assessed with preoperative CT-based visceral fat ratio quantification as well as tumor metabolic gene expression, predicts sex-dependent overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). Materials and Methods: This was a retrospective analysis of preoperative CT in 98 male and 107 female patients with PDAC. Relative visceral fat (rVFA; visceral fat normalized to total fat) was measured automatically using software and corrected manually. Median and optimized rVFA thresholds were determined according to published methods. Kaplan Meier and log-rank tests were used to estimate OS. Multivariate models were developed to identify interactions between sex, rVFA, and OS. Unsupervised gene expression analysis of PDAC tumors from The Cancer Genome Atlas (TCGA) was performed to identify metabolic pathways with similar survival patterns to rVFA. Results: Optimized preoperative rVFA threshold of 38.9% predicted significantly different OS in females with a median OS of 15 months (above threshold) vs 24 months (below threshold; p = 0.004). No significant threshold was identified in males. This female-specific significance was independent of age, stage, and presence of chronic pancreatitis (p = 0.02). Tumor gene expression analysis identified female-specific stratification from a five-gene signature of glutathione S-transferases. This was observed for PDAC as well as clear cell renal carcinoma and glioblastoma. Conclusion: CT-based assessments of visceral fat can predict pancreatic cancer OS in females. Glutathione S-transferase expression in tumors predicts female-specific OS in a similar fashion. Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joseph Ippolito reports the analysis software license was provided by Vital Images Inc. (Copyright © 2024 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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