Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients.
Heat shock proteins (HSPs) are components of a physiologic stress response that are also over-expressed in various cancers including non-small cell lung cancer (NSCLC). During NSCLC serum-antibody screening of a NSCLC cDNA T7 phage library for immunogenic proteins we isolated HSP70 and HSP90 proteins. Isolation of these proteins suggested that corresponding antibodies could be elevated in NSCLC patient sera, a novel finding that could pilot their use as markers of NSCLC. We showed histochemically that patient sera were more reactive with each phage-expressed protein than normal sera. Antibody affinity for each phage-expressed protein was confirmed by limiting the dilution of individual sera assayed by Ab enzyme-linked immunosorbent assay (ELISA). Sera from 49 NSCLC patients assayed by Ab ELISA and normalized to 40 controls showed that HSP70 antibodies were significantly greater in patient sera than in normals (P=0.0002), while HSP90 antibodies were not significantly different (P=0.11). Analysis of the results with logistic regression and receiver operating characteristics (ROC) curves showed that HSP70 antibodies were modest markers of NSCLC (sensitivity 0.74 and specificity 0.73; area under the curve or AUC=0.731), while HSP90 antibodies appeared to be poor in both criteria with an AUC of 0.602. Further evaluation of HSP70 antibodies as potential markers of disease may be rational.
Zhong
Li
L
Division of Pulmonary and Critical Care Medicine, Lexington Veteran's Administration Medical Center, University of Kentucky, Chandler Medical Center, 800 Rose Street, Room MN 614, Lexington, KY 40536, USA. lzhong@uky.edu
Peng
Xuejun
X
Hidalgo
Giovanna E
GE
Doherty
Dennis E
DE
Stromberg
Arnold J
AJ
Hirschowitz
Edward A
EA
D000906:Antibodies / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology*; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology*; D012016:Reference Values; D012044:Regression Analysis
D000906:Antibodies; D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins