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Proteomic profiling of pre-treatment serum from HIV infected patients identifies candidate markers predictive of lymphoma development.

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Vase MØ, Ludvigsen M, Bendix K, Hamilton-Dutoit S, Mller MB, Pedersen C, Pedersen G, Obel N, Larsen CS, d'Amore F, Honoré B,


Vase MØ, Ludvigsen M, Bendix K, Hamilton-Dutoit S, Mller MB, Pedersen C, Pedersen G, Obel N, Larsen CS, d'Amore F, Honoré B, (click to view)

Vase MØ, Ludvigsen M, Bendix K, Hamilton-Dutoit S, Mller MB, Pedersen C, Pedersen G, Obel N, Larsen CS, d'Amore F, Honoré B,

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AIDS (London, England) 2016 5 12()

Abstract
OBJECTIVE
HIV infected individuals have an increased risk of developing lymphoma. We sought to identify markers predictive of lymphoma development by comparing protein expression patterns in serum obtained at the time of HIV-diagnosis from patients who later developed malignant lymphoma or benign lymphadenopathy, with samples from patients with no subsequent history of neoplasia.

DESIGN
All patients were identified retrospectively from the Danish HIV Cohort.

METHODS
Serum samples (N = 21) obtained at time of HIV diagnosis were subjected to high-resolution two-dimensional gel electrophoresis. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue micro-array (TMA) containing diagnostic HIV-lymphoma tissue samples (N = 40) was used to investigate immunohistochemical expression of markers in tumoral lesions.

RESULTS
Fourteen differentially expressed protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (p < 0.0001). Serum amyloid A-2 was increased almost 10-fold in patients with subsequent lymphoma compared with patients without subsequent lymphoma. In the TMA, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). CONCLUSIONS
We identified several differentially expressed protein spots, present already at time of HIV diagnosis. Analysis of biological differences correlating to lymphoma development at this early stage of a possible malignant transformation, may lead to the identification of predictive markers. Further investigation of the potential clinical application of differentially expressed proteins as risk stratification markers for monitoring HIV-positive individuals is warranted.

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