Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

Maja Ølholm Vase; Maja Ludvigsen; Knud Bendix; Stephen Hamilton-Dutoit; Michael Boe Mller; Court Pedersen; Gitte Pedersen; Niels Obel; Carsten Schade Larsen; Francesco d'Amore; Bent Honoré

doi:10.1097/QAD.0000000000001152

Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

Maja Ølholm Vase, Maja Ludvigsen, Knud Bendix, Stephen Hamilton-Dutoit, Michael Boe Mller, Court Pedersen, Gitte Pedersen, Niels Obel, Carsten Schade Larsen, Francesco d'Amore, Bent Honoré

Department of Clinical Medicine

2 Citations (Scopus)

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 microarray, containing diagnostic HIV-lymphoma tissue samples (N=40), was used to investigate immunohistochemical expression of markers in tumoural 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 tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). Conclusion: We identified several differentially expressed protein spots present already at the 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.

Original language	English
Journal	AIDS
Volume	30
Issue number	12
Pages (from-to)	1889-1898
Number of pages	10
ISSN	0269-9370
DOIs	https://doi.org/10.1097/QAD.0000000000001152
Publication status	Published - 31 Jul 2016

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title = "Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development",

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 microarray, containing diagnostic HIV-lymphoma tissue samples (N=40), was used to investigate immunohistochemical expression of markers in tumoural 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 tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). Conclusion: We identified several differentially expressed protein spots present already at the 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.",

author = "Vase, {Maja {\O}lholm} and Maja Ludvigsen and Knud Bendix and Stephen Hamilton-Dutoit and Mller, {Michael Boe} and Court Pedersen and Gitte Pedersen and Niels Obel and Larsen, {Carsten Schade} and Francesco d'Amore and Bent Honor{\'e}",

year = "2016",

month = jul,

day = "31",

doi = "10.1097/QAD.0000000000001152",

language = "English",

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pages = "1889--1898",

journal = "AIDS",

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T1 - Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

AU - Vase, Maja Ølholm

AU - Ludvigsen, Maja

AU - Bendix, Knud

AU - Hamilton-Dutoit, Stephen

AU - Mller, Michael Boe

AU - Pedersen, Court

AU - Pedersen, Gitte

AU - Obel, Niels

AU - Larsen, Carsten Schade

AU - d'Amore, Francesco

AU - Honoré, Bent

PY - 2016/7/31

Y1 - 2016/7/31

N2 - 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 microarray, containing diagnostic HIV-lymphoma tissue samples (N=40), was used to investigate immunohistochemical expression of markers in tumoural 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 tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). Conclusion: We identified several differentially expressed protein spots present already at the 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.

AB - 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 microarray, containing diagnostic HIV-lymphoma tissue samples (N=40), was used to investigate immunohistochemical expression of markers in tumoural 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 tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). Conclusion: We identified several differentially expressed protein spots present already at the 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.

U2 - 10.1097/QAD.0000000000001152

DO - 10.1097/QAD.0000000000001152

M3 - Journal article

C2 - 27177314

SN - 0269-9370

VL - 30

SP - 1889

EP - 1898

JO - AIDS

JF - AIDS

IS - 12

ER -

Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

Abstract

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