title: Identification of novel candidate circulating biomarkers for malignant soft tissue sarcomas: Correlation with metastatic progression.
abstract: Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors for which identification and validation of biological markers may improve clinical management. The fraction of low-molecular-weight (LMW) circulating proteins and fragments of proteins is a rich source of new potential biomarkers. To identify circulating biomarkers useful for STS early diagnosis and prognosis, we analyzed 53 high-grade STS sera using hydrogel core-shell nanoparticles that selectively entrap LMW proteins by size exclusion and affinity chromatography, protect them from degradation and amplify their concentration for mass spectrometry detection. Twenty-two analytes mostly involved in inflammatory and immunological response, showed a progressive increase from benign to malignant STS with a relative difference in abundance, more than 50% when compared to healthy control. 16 of these were higher in metastatic compared to non-metastatic tumors. Cox's regression analysis revealed a statistical significant association between the abundance of lactotransferrin (LTF) and complement factor H-related 5 (CFHR5) and risk of metastasis. In particular, CFHR5 was associated with the risk of metastasis. The role of circulating proteins involved in metastatic progression will be crucial for a better understanding of STS biology and patient management.
authors.affiliation: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.|Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Amalia
authors.initials: A
authors.lastname: Conti
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fredolini
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Davide
authors.initials: D
authors.lastname: Tamburro
authors.affiliation: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Magagnoli
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Lance A
authors.initials: LA
authors.lastname: Liotta
authors.affiliation: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Picci
authors.affiliation: Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Luchini
authors.affiliation: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Maria Serena
authors.initials: MS
authors.lastname: Benassi
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins / Q000032:analysis*; D003165:Complement System Proteins / Q000032:analysis; D042241:Early Diagnosis; D006801:Humans; D007781:Lactoferrin / Q000032:analysis / Q000097:blood; D053758:Nanoparticles / Q000737:chemistry; D009362:Neoplasm Metastasis / Q000175:diagnosis; D011379:Prognosis; D012509:Sarcoma / Q000097:blood* / Q000175:diagnosis*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; C432223:CFHR5 protein, human; D003165:Complement System Proteins; D007781:Lactoferrin
keywords: Biomedicine; ESI-LC/MSMS; Metastasis; Nanoparticles; Serum biomarkers; Soft tissue sarcomas