title: Gene expression profiling of peripheral blood cells: new insights into Ewing sarcoma biology and clinical applications.
abstract: Ewing sarcoma (ES) is a group of highly aggressive small round cell tumors of bone or soft tissue with high metastatic potential and low cure rate. ES tumors are associated with a rapid osteolysis and necrosis. The currently accepted clinical prognostic parameters do not accurately predict survival of high-risk patients. Moreover, neither the subtype of EWS-FLI1/ERG in the tumor, nor the detection of fusion transcripts in the peripheral blood (PB) samples, has prognostic value in ES patients. We evaluated the prevalence of circulating tumor cells (CTCs) in 34 adult ES patients. Since CTCs were confirmed in only small subset of patients, we further explored the expression profiles of PB leukocytes using a panel of genes associated with immune system status and increased tumor invasiveness. Moreover, we analyzed the alterations of the routine blood tests in the examined cohort of patients and correlated our findings with the clinical outcome. A uniform decrease in ZAP70 expression in PB cells among all ES patients, as compared to healthy individuals, was observed. Monocytosis and the abnormal expression of CDH2 and CDT2 genes in the PB cells significantly correlated with poor prognosis in ES patients. Our study supports the previously proposed hypothesis of systemic nature of ES. Based on the PB cell expression profiles, we propose a mechanism by which immune system may be involved in intensification of osteoclastogenesis and disease progression in ES patients. Moreover, we demonstrate the prognostic value of molecular PB testing at the time of routine histopathological diagnosis.
authors.affiliation: Department of Molecular and Translational Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, 5 W.K. Roentgen Street, 02-781, Warsaw, Poland, joanna.przybyl@coi.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Przybyl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kozak
authors.forename: Hanna
authors.initials: H
authors.lastname: Kosela
authors.forename: Slawomir
authors.initials: S
authors.lastname: Falkowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Switaj
authors.forename: Iwona
authors.initials: I
authors.lastname: Lugowska
authors.forename: Anna
authors.initials: A
authors.lastname: Szumera-Cieckiewicz
authors.forename: Konrad
authors.initials: K
authors.lastname: Ptaszynski
authors.forename: Beata
authors.initials: B
authors.lastname: Grygalewicz
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chechlinska
authors.forename: Barbara
authors.initials: B
authors.lastname: Pienkowska-Grela
authors.forename: Maria
authors.initials: M
authors.lastname: Debiec-Rychter
authors.forename: Janusz A
authors.initials: JA
authors.lastname: Siedlecki
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001773:Blood Cells / Q000473:pathology / Q000502:physiology*; D001859:Bone Neoplasms / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015820:Cadherins / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011379:Prognosis; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics; D034802:RNA-Binding Protein EWS / Q000235:genetics; D012512:Sarcoma, Ewing / Q000097:blood / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000097:blood / Q000235:genetics
chemical_list: D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; C429530:DTL protein, human; C450460:EWS-ERG fusion protein, human; C106031:EWS-FLI fusion protein; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human