title: 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.
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, 00014, Helsinki, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Savola
authors.forename: Arto
authors.initials: A
authors.lastname: Klami
authors.forename: Samuel
authors.initials: S
authors.lastname: Myllykangas
authors.forename: Cristina
authors.initials: C
authors.lastname: Manara
authors.forename: Katia
authors.initials: K
authors.lastname: Scotlandi
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.forename: Sakari
authors.initials: S
authors.lastname: Knuutila
authors.forename: Jukka
authors.initials: J
authors.lastname: Vakkila
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