High Expression of Complement Component 5 ( C5 ) at Tumor Site Associates with Superior Survival in Ewing's Sarcoma Family of Tumour Patients

Abstract

Background . Unlike in most adult-onset cancers, an association between typical paediatric neoplasms and inflammatory triggers is rare. We studied whether immune system-related genes are activated and have prognostic significance in Ewing's sarcoma family of tumors (ESFTs). Method . Data analysis was performed on gene expression profiles of 44 ESFT patients, 11 ESFT cell lines, and 18 normal skeletal muscle samples. Differential expression of 238 inflammation and 299 macrophage-related genes was analysed by t -test, and survival analysis was performed according to gene expression. Results . Inflammatory genes are activated in ESFT patient samples, as 38 of 238 (16%) inflammatory genes were upregulated ( P < 0.001 ) when compared to cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage-related gene expression with 58 of 299 (19%) of genes upregulated ( P < 0.001 ) . High expression of complement component 5 ( C5 ) correlated with better event-free ( P = 0.01 ) and overall survival ( P = 0.004 ) in a dose-dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on an independent ESFT tumour tissue microarray. Conclusion . Immune system-related gene activation is observed in ESFT patient samples, and prognostically significant inflammatory genes ( C5, JAK1 , and IL8 ) for ESFT were identified.