title: Serum levels of cytoplasmic melanoma-associated antigen at diagnosis may predict clinical relapse in neuroblastoma patients.
abstract: The high molecular weight melanoma-associated antigen (HMW-MAA) and the cytoplasmic melanoma-associated antigen (cyt-MAA/LGALS3BP) are expressed in melanoma. Their serum levels are increased in melanoma patients and correlate with clinical outcome. We investigated whether these molecules can serve as prognostic markers for neuroblastoma (NB) patients. Expression of cyt-MAA and HMW-MAA was evaluated by flow cytometry in NB cell lines, patients' neuroblasts ((FI)-NB), and short-term cultures of these latter cells (cNB). LGALS3BP gene expression was evaluated by RT-qPCR on (FI)-NB, cNB, and primary tumor specimens. Soluble HMW-MAA and cyt-MAA were tested by ELISA. Cyt-MAA and HMW-MAA were expressed in NB cell lines, cNB, and (FI)-NB samples. LGALS3BP gene expression was higher in primary tumors and cNB than in (FI)-NB samples. Soluble cyt-MAA, but not HMW-MAA, was detected in NB cell lines and cNBs supernatants. NB patients' serum levels of both antigens were higher than those of the healthy children. High cyt-MAA serum levels at diagnosis associated with higher incidence of relapse, independently from other known risk factors. In conclusion, both HMW-MAA and cyt-MAA antigens, and LGALS3BP gene, were expressed by NB cell lines and patients' neuroblasts, and both antigens' serum levels were increased in NB patients. Elevated serum levels of cyt-MAA at diagnosis correlated with relapse, supporting that cyt-MAA may serve as early serological biomarker to individuate patients at higher risk of relapse that may require a more careful follow-up, after being validated in a larger cohort of patients at different time-points during follow-up. Given its immunogenicity, cyt-MAA may also be a potential target for NB immunotherapy.
authors.affiliation: Laboratory of Oncology, G. Gaslini Children's Hospital, Largo G. Gaslini 5, 16148 Genoa, Italy. fabiomorandi@ospedale-gaslini.ge.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Corrias
authors.forename: Isabella
authors.initials: I
authors.lastname: Levreri
authors.forename: Paola
authors.initials: P
authors.lastname: Scaruffi
authors.forename: Lizzia
authors.initials: L
authors.lastname: Raffaghello
authors.forename: Barbara
authors.initials: B
authors.lastname: Carlini
authors.forename: Paola
authors.initials: P
authors.lastname: Bocca
authors.forename: Ignazia
authors.initials: I
authors.lastname: Prigione
authors.forename: Sara
authors.initials: S
authors.lastname: Stigliani
authors.forename: Loredana
authors.initials: L
authors.lastname: Amoroso
authors.forename: Soldano
authors.initials: S
authors.lastname: Ferrone
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D002469:Cell Separation; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D009447:Neuroblastoma / Q000097:blood* / Q000401:mortality; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099216:Chondroitin Sulfate Proteoglycan 4; D016326:Extracellular Matrix Proteins
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C081856:LGALS3BP protein, human; D016326:Extracellular Matrix Proteins