Inflammatory gene profiling of Ewing sarcoma family of tumors (set A)

ABSTRACT: Purpose: 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 sarcoma family of tumours (ESFT). Experimental design: Data-analysis was performed on gene expression profiles of 44 ESFT patient, 11 ESFT cell line, and 18 normal muscle tissue samples. 238 inflammation related genes were selected based on literature and a macrophage gene expression signature was derived from SymAtlas. Differential expression of the 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 significantly upregulated (p<0.001) when compared to ESFT cell lines. This inflammatory gene activation was characterized by significant enrichment of macrophage related gene expression with 58 of 299 (19%) of these genes being upregulated (p<0.001). By combining expression data from ESFT patients, cell lines and muscle tissue samples we were able to identify a total of 32 presumptive inflammatory genes that characterize and distinguish tumour site in vivo from surrounding normal tissues. High expression of C5 correlated with better event free (p=0.01) and overall survival (p=0.004) in dose dependent manner. C5 and its receptor C5aR1 expression was verified at protein level by immunohistochemistry on tumor tissue microarray. Also, high expression of JAK1 correlated with favourable overall survival (p=0.04) and high expression of IL8, derived presumably from infiltrating immune cells, resulted in poor overall survival in Ewing sarcoma (p=0.04). Conclusions: Immune system related gene activation is observed in ESFT patient samples and several prognostically significant inflammatory genes (C5, JAK1 and IL8) for ESFT were identified. 44 Ewing sarcoma family of tumor patient and 11 cell line samples were analysed for their gene expression.

ORGANISM(S): Homo sapiens

SUBMITTER: Suvi Savola 

PROVIDER: E-GEOD-17618 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress