Tumor and Macrophage Gene Expression Patterns Predict Metastasis and Survival in Children with Neuroblastoma
(ChemotherapyAdvisor) – Gene expression patterns in MYCN-nonamplified metastatic neuroblastoma (NBL-NA) and tumor-associated macrophages are associated with metastasis risk and might explain age-associated differences in NBL-NA patient prognosis, according to a study published in the Journal of Clinical Oncology.
The study provides “the first evidence of a role for intratumor inflammation in metastatic neuroblastoma and provides a validated prognostic signature for children with metastatic NBL-NA,” reported lead author Shahab Asgharzadeh, MD, Children's Hospital Los Angeles, Los Angeles, California, and coauthors.
The team found metastatic neuroblastomas to have higher levels of tumor infiltration by activated macrophages (identified with CD163 immunohistochemical staining) than locoregional tumors (t test P = 0.003; Bonferroni-adjusted P<0.017).
Expression analysis of 133 genes also revealed that metastatic tumors diagnosed in children ≥18 months had higher levels of inflammation-associated gene expression than did the tumors diagnosed among younger children, the authors reported.
Children diagnosed with NBL-NA at ≥18 months have high rates of relapse, while those diagnosed at <18 months are “nearly always cured,” Asgharzadeh and coauthors noted.
Subsequent analysis of the expression patterns for 31 tumor genes and 13 tumor-associated macrophage genes identified a prognostic gene expression signature involving 9 tumor genes and 5 macrophage genes. When tumors were categorized as high-risk or low-risk using the 14-gene risk signature score, progression-free survival (PFS) was superior among patients with low-risk signatures (72% vs. 16% 5-year PFS; P<0.001).
“The increase in expression of inflammation-related genes in children age ≥18 months with poor outcome allows the identification of a subgroup of patients at extremely high risk who may benefit from treatments targeting the tumor microenvironment along with tumor cells,” Asgharzadeh and coauthors suggested. “The recent success of therapies directed at tumor-associated immune system cells in adult cancers suggests opportunities for their application in children with neuroblastoma.”