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A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma

Tarhini, AA and Lin, Y and Yeku, O and LaFramboise, WA and Ashraf, M and Sander, C and Kirkwood, JM and Lee, S (2014) A four-marker signature of TNF-RII, TGF-α, TIMP-1 and CRP is prognostic of worse survival in high-risk surgically resected melanoma. Journal of Translational Medicine, 12 (1).

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Abstract

Background: E1694 tested GM2-KLH-QS21 vaccine versus high-dose interferon-α2b (HDI) as adjuvant therapy for operable stage IIB-III melanoma. We tested banked serum specimens from patients in the vaccine arm of E1694 for prognostic biomarkers.Methods: Aushon Multiplex Platform was used to quantitate baseline serum levels of 115 analytes from 40 patients. Least absolute shrinkage and selection operator proportional hazard regression (Lasso PH) was used to select markers that are most informative for relapse-free survival (RFS) and overall survival (OS). Regular Cox PH models were then fit with the markers selected by the Lasso PH. Survival receiver operating characteristic (ROC) analysis was used to evaluate the ability of the models to predict 1-year RFS and 5-year OS.Results: Four markers that include Tumor Necrosis Factor alpha Receptor II (TNF-RII), Transforming Growth Factor alpha (TGF-α), Tissue Inhibitor of Metalloproteinases 1 (TIMP-1), and C-reactive protein (CRP) were found to be most informative for the prediction of OS (high levels correlate with worse prognosis). The dichotomized risk score based on the four markers could significantly separate the OS curves (p = 0.0005). When using the four-marker PH model to predict 5-year OS, we achieved an area under the curve (AUC) of 89% (cross validated AUC = 72%). High baseline TNF-RII was also significantly associated with worse RFS. The RFS with high (above median) TNF-RII was significantly lower than low TNF-RII (p = 0.01).Conclusions: The biomarker signature consisting of TNFR-II, TGF-α, TIMP-1 and CRP is significantly prognostic of survival in patients with high-risk melanoma and warrants further investigation. © 2014 Tarhini et al.; licensee BioMed Central Ltd.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Tarhini, AAaat8@pitt.eduAAT8
Lin, Yyal14@pitt.eduYAL140000-0001-9413-3960
Yeku, O
LaFramboise, WAwal9@pitt.eduWAL90000-0002-6024-810X
Ashraf, M
Sander, Ccas32@pitt.eduCAS32
Kirkwood, JMkirkwood@pitt.eduKIRKWOOD
Lee, S
Centers: Other Centers, Institutes, or Units > Pittsburgh Cancer Institute
Date: 23 January 2014
Date Type: Publication
Journal or Publication Title: Journal of Translational Medicine
Volume: 12
Number: 1
DOI or Unique Handle: 10.1186/1479-5876-12-19
Schools and Programs: Graduate School of Public Health > Biostatistics
School of Medicine > Computational Biology
School of Medicine > Medicine
Refereed: Yes
Date Deposited: 02 Dec 2016 20:32
Last Modified: 01 Nov 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/29608

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