title: Early detection of head and neck cancer: development of a novel screening tool using multiplexed immunobead-based biomarker profiling.
abstract: Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease that has been linked to altered immune, inflammatory, and angiogenesis responses. A better understanding of these aberrant responses might improve early detection and prognosis of SCCHN and provide novel therapeutic targets. Previous studies examined the role of multiplexed serum biomarkers in small cohorts or SCCHN sera. We hypothesized that an expanded panel comprised of multiple cytokines, chemokines, growth factors, and other tumor markers, which individually may show some promising correlation with disease status, might provide higher diagnostic power if used in combination. Thus, we evaluated a novel multianalyte LabMAP profiling technology that allows simultaneous measurement of multiple serum biomarkers. Concentrations of 60 cytokines, growth factors, and tumor antigens were measured in the sera of 116 SCCHN patients before treatment (active disease group), 103 patients who were successfully treated (no evidence of disease group), and 117 smoker controls without evidence of cancer. The multimarker panel offering the highest diagnostic power was comprised of 25 biomarkers, including epidermal growth factor, epidermal growth factor receptor, interleukin (IL)-8, tissue plasminogen activator inhibitor-1, alpha-fetoprotein, matrix metalloproteinase-2, matrix metalloproteinase-3, IFN-alpha, IFN-gamma, IFN-inducible protein-10, regulated on activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein-1alpha, IL-7, IL-17, IL-1 receptor-alpha, IL-2 receptor, granulocyte colony-stimulating factor, mesothelin, insulin-like growth factor binding protein 1, E-selectin, cytokeratin-19, vascular cell adhesion molecule, and cancer antigen-125. Statistical analysis using an ADE algorithm resulted in a sensitivity of 84.5%, specificity of 98%, and 92% of patients in the active disease group correctly classified from a cross-validation serum set. The data presented show that simultaneous testing using a multiplexed panel of serum biomarkers may present a promising new approach for the early detection of head and neck cancer.
authors.affiliation: Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Faina
authors.initials: F
authors.lastname: Linkov
authors.forename: Alex
authors.initials: A
authors.lastname: Lisovich
authors.forename: Zoya
authors.initials: Z
authors.lastname: Yurkovetsky
authors.forename: Adele
authors.initials: A
authors.lastname: Marrangoni
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Velikokhatnaya
authors.forename: Brian
authors.initials: B
authors.lastname: Nolen
authors.forename: Matthew
authors.initials: M
authors.lastname: Winans
authors.forename: William
authors.initials: W
authors.lastname: Bigbee
authors.forename: Jill
authors.initials: J
authors.lastname: Siegfried
authors.forename: Anna
authors.initials: A
authors.lastname: Lokshin
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis*; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood*; D016207:Cytokines / Q000097:blood; D042241:Early Diagnosis; D005260:Female; D006258:Head and Neck Neoplasms / Q000097:blood / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay; D008297:Male; D008403:Mass Screening; D008863:Microspheres; D008875:Middle Aged; D011237:Predictive Value of Tests; D012907:Smoking
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D018925:Chemokines; D016207:Cytokines