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. 2012 Aug 27;30(28):3525–3532. doi: 10.1200/JCO.2011.40.9169

Fig 3.

Fig 3.

Inflammation- and tumor-related gene-gene correlations. (A) Heatmap of the Spearman rank correlation matrix of the 14 genes in the metastatic MYCN-nonamplified neuroblastoma (NBL-NA) signature. Pairwise rank correlation analyses were performed for all 14 genes and age at diagnosis. The patterns of correlation using samples from Children's Cancer Group (CCG) patients diagnosed at age ≥ 18 months were similar to the pairwise rank correlations obtained using samples from the German Society for Pediatric Oncology-Hematology and Children's Oncology Group validation cohorts (Data Supplement). Red represents positive rank correlation level above zero (white color) for a given gene pair, and blue represents negative rank correlation level. The inflammation-related genes (FCGR3/CD16, CD33, CD14, IL6R, IL10) show high levels of correlation across all cohorts. NTRK2 has the strongest correlation of any tumor cell–related gene with inflammation-related genes. (B) Expression of inflammation-related genes is predominantly present in neuroblastoma tumors and not on cell lines. Normalized expression (ΔCT) values of four of the five inflammation-related genes (CD14, FCGR3/CD16, IL10, IL6R) in the CCG tumors (n = 133) were compared with six neuroblastoma MYCN nonamplified cell lines (CHLA-15, CHLA-20, CHLA-255, CHLA-42, CHLA-90, LAN-6). Data on the cell lines were generated on a TaqMan low-density array (Life Technologies, Carlsbad, CA) card that did not include CD33 probes. On average, there was 309-, 271-, seven-, and five-fold higher expression of CD14, FCGR3/CD16, IL10, and IL6R in tumors than in cell lines, respectively, suggesting that these genes are primarily expressed by tumor-associated inflammatory cells. (C) Scatter diagram of expression of CD14, a macrophage marker, and IL6R reveals a high correlation in patients with metastatic NBL-NA. (D) Similarly, NTRK2, a tumor cell–related gene, shows moderate correlation with expression of IL6R, an inflammation-related gene. Gray, patients diagnosed at age < 18 months with metastatic NBL-NA; blue, disease-free patients diagnosed at age ≥ 18 months; gold, disease progression in patients diagnosed at age ≥ 18 months.