title: Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival.
abstract: The prognosis of children with metastatic neuroblastoma (NB) > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1), Granzyme B (GRMB), and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.). Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.
authors.affiliation: Physiopathology of Human Reproduction, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Stigliani
authors.affiliation: Laboratory of Biotherapy, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Croce
authors.affiliation: Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Morandi
authors.affiliation: Physiopathology of Human Reproduction, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Scaruffi
authors.affiliation: Laboratory of Biotherapy, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rigo
authors.affiliation: Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Carlini
authors.affiliation: Oncology Unit, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Manzitti
authors.affiliation: Epidemiology, Biostatistics and Committees Unit, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Gigliotti
authors.affiliation: Neuroblastoma Laboratory, Pediatric Research Institute, Fondazione Città della Speranza, 35127 Padua, Italy.
authors.forename: Gian Paolo
authors.initials: GP
authors.lastname: Tonini
authors.affiliation: Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Vito
authors.initials: V
authors.lastname: Pistoia
authors.affiliation: Laboratory of Biotherapy, IRCCS A.O.U. San Martino-IST, 16132 Genoa, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Ferrini
authors.affiliation: Laboratory of Oncology, IRCCS Istituto Giannina Gaslini, 16148 Genoa, Italy.
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Corrias
mesh_terms: D001119:Arginase / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D030541:Databases, Genetic; D018572:Disease-Free Survival; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009447:Neuroblastoma / Q000235:genetics*; D012307:Risk Factors; D018709:Statistics, Nonparametric
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018950:Lipopolysaccharide Receptors; C574619:ARG1 protein, human; D001119:Arginase