Figure 5.

Prognostic significance of ABCC gene expression in neuroblastoma. A) Combined expression of the ABCC1, ABCC3 and ABCC4 genes and cumulative event-free survival (EFS) in 209 patients with neuroblastoma. Patients were categorized into eight clusters on the basis of their combined ABCC1, ABCC3, and ABCC4 expression pattern. Kaplan–Meier survival analysis of these clusters revealed three statistically distinct groupings (Groups A, B, and C), which were associated with the risk of relapse associated with individual ABCC gene expression. Group A included only those patients whose tumors displayed low levels of ABCC1 and ABCC4 and high levels of ABCC3, reflecting “favorable” ABCC gene expression. Group B consisted of patients whose tumors displayed only one unfavorable risk factor with respect to the three ABCC genes analyzed (ie, ABCC1 high, ABCC4 high, or ABCC3 low), and Group C comprised patients whose tumors exhibited two or more unfavorable ABCC risk factors. Similar associations between combined ABCC gene expression and increasingly poor outcome were also observed in subgroups of patients (B) with stage 3 or 4 disease or (C) whose tumors lacked MYCN amplification. D) Combined expression of the ABCC1, ABCC3, and ABCC4 genes and cumulative EFS in 251 neuroblastoma patient samples analyzed by Oberthuer et al. (27). Patients in the Oberthuer et al. (27) cohort were categorized into eight groups as described for panel (A) above. These groupings were also strongly predictive of EFS in subgroups of patients (E) with unfavorable (stages 3 and 4) disease or (F) with non–MYCN-amplified disease. At 0, 3, and 6 years from diagnosis [Panels (A), (B), and (C)], or 0, 5, and 10 years from diagnosis [Panels (D), (E), and (F)], the number of patients at risk of relapse are shown. ABCC = ATP-binding cassette, subfamily C; MYCN = v-myc myelocytomatosis viral related oncogene, neuroblastoma derived.