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- Olin, JW, et al.
(författare)
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A plasma proteogenomic signature for fibromuscular dysplasia
- 2020
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Ingår i: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 116:1, s. 63-77
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Tidskriftsartikel (refereegranskat)abstract
- AimsFibromuscular dysplasia (FMD) is a poorly understood disease that predominantly affects women during middle-life, with features that include stenosis, aneurysm, and dissection of medium-large arteries. Recently, plasma proteomics has emerged as an important means to understand cardiovascular diseases. Our objectives were: (i) to characterize plasma proteins and determine if any exhibit differential abundance in FMD subjects vs. matched healthy controls and (ii) to leverage these protein data to conduct systems analyses to provide biologic insights on FMD, and explore if this could be developed into a blood-based FMD test.Methods and resultsFemales with ‘multifocal’ FMD and matched healthy controls underwent clinical phenotyping, dermal biopsy, and blood draw. Using dual-capture proximity extension assay and nuclear magnetic resonance-spectroscopy, we evaluated plasma levels of 981 proteins and 31 lipid sub-classes, respectively. In a discovery cohort (Ncases = 90, Ncontrols = 100), we identified 105 proteins and 16 lipid sub-classes (predominantly triglycerides and fatty acids) with differential plasma abundance in FMD cases vs. controls. In an independent cohort (Ncases = 23, Ncontrols = 28), we successfully validated 37 plasma proteins and 10 lipid sub-classes with differential abundance. Among these, 5/37 proteins exhibited genetic control and Bayesian analyses identified 3 of these as potential upstream drivers of FMD. In a 3rd cohort (Ncases = 506, Ncontrols = 876) the genetic locus of one of these upstream disease drivers, CD2-associated protein (CD2AP), was independently validated as being associated with risk of having FMD (odds ratios = 1.36; P = 0.0003). Immune-fluorescence staining identified that CD2AP is expressed by the endothelium of medium-large arteries. Finally, machine learning trained on the discovery cohort was used to develop a test for FMD. When independently applied to the validation cohort, the test showed a c-statistic of 0.73 and sensitivity of 78.3%.ConclusionFMD exhibits a plasma proteogenomic and lipid signature that includes potential causative disease drivers, and which holds promise for developing a blood-based test for this disease.
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| 2. |
- Ivanics, Tommy, et al.
(författare)
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Living Donor Liver Transplantation for Hepatocellular Carcinoma Within and Outside Traditional Selection Criteria
- 2024
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Ingår i: Annals of Surgery. - : Wolters Kluwer. - 0003-4932 .- 1528-1140. ; 279:1, s. 104-111
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To evaluate long-term oncologic outcomes of patients post-living donor liver transplantation (LDLT) within and outside standard transplantation selection criteria and the added value of the incorporation of the New York-California (NYCA) score.Background:LDLT offers an opportunity to decrease the liver transplantation waitlist, reduce waitlist mortality, and expand selection criteria for patients with hepatocellular carcinoma (HCC).Methods:Primary adult LDLT recipients between October 1999 and August 2019 were identified from a multicenter cohort of 12 North American centers. Posttransplantation and recurrence-free survival were evaluated using the Kaplan-Meier method.Results:Three hundred sixty LDLTs were identified. Patients within Milan criteria (MC) at transplantation had a 1, 5, and 10-year posttransplantation survival of 90.9%, 78.5%, and 64.1% versus outside MC 90.4%, 68.6%, and 57.7% (P = 0.20), respectively. For patients within the University of California San Francisco (UCSF) criteria, respective posttransplantation survival was 90.6%, 77.8%, and 65.0%, versus outside UCSF 92.1%, 63.8%, and 45.8% (P = 0.08). Fifty-three (83%) patients classified as outside MC at transplantation would have been classified as either low or acceptable risk with the NYCA score. These patients had a 5-year overall survival of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplantation would have been classified as a low or acceptable risk with a 5-year overall survival of 65.3%.Conclusions:Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-year rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.
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