TY - JOUR
T1 - Proteomic Profiling of Lymph Nodes Differentiates Classic Hodgkin Lymphoma With and Without Skeletal Involvement
AU - Andersen, Maja Dam
AU - Wolter, Katharina
AU - Enemark, Marie Beck Hairing
AU - Pedersen, Mette Abildgaard
AU - Gormsen, Lars Christian
AU - Lauridsen, Kristina Lystlund
AU - Starklint, Jørn
AU - Hamilton-Dutoit, Stephen Jacques
AU - d'Amore, Francesco
AU - Ludvigsen, Maja
AU - Honoré, Bent
AU - Kamper, Peter
N1 - © 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.
PY - 2025/1
Y1 - 2025/1
N2 - Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.
AB - Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown. We investigated protein expression in diagnostic lymph node biopsies from CHL patients with and without skeletal involvement at diagnosis to identify potential markers of skeletal disease. Protein expression patterns in diagnostic formalin-fixed paraffin-embedded lymphoma lymph node samples from CHL patients were analyzed by nano-liquid chromatography-tandem mass spectrometry. Patients were grouped according to skeletal involvement, which was defined as the presence of one or more FDG-avid lesions on a diagnostic FDG-PET/CT scan. Protein profiles identified patients with skeletal disease at diagnosis and showed disrupted cellular pathways, including immune system processes, cell adhesion, and cell growth/survival. Immunohistochemical evaluation also demonstrated differential expressions of angiotensin-converting enzyme (ACE), intercellular adhesion molecule 3 (ICAM3), integrin alpha-X (ITGAX), and calreticulin (CALR). In conclusion, proteomics identified altered protein expression profiles in lymph nodes among CHL cases presenting with disease disseminated to the skeletal system, which implies altered disease pathogenesis for these patients.
KW - Adult
KW - Aged
KW - Biomarkers, Tumor/metabolism
KW - Bone Neoplasms/diagnosis
KW - Female
KW - Hodgkin Disease/diagnosis
KW - Humans
KW - Lymph Nodes/pathology
KW - Male
KW - Middle Aged
KW - Positron Emission Tomography Computed Tomography
KW - Prognosis
KW - Proteome
KW - Proteomics/methods
KW - proteomics
KW - bone
KW - classic Hodgkin lymphoma (CHL)
KW - nLC-MS/MS
UR - http://www.scopus.com/inward/record.url?scp=85206086991&partnerID=8YFLogxK
U2 - 10.1111/ejh.14326
DO - 10.1111/ejh.14326
M3 - Journal article
C2 - 39394762
SN - 0902-4506
VL - 114
SP - 173
EP - 185
JO - European Journal of Haematology
JF - European Journal of Haematology
IS - 1
ER -