Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera.
OBJECTIVE
We have implemented a high throughput platform for quantitative analysis of serum autoantibodies, which we have applied to lung cancer for discovery of novel antigens and for validation in prediagnostic sera of autoantibodies to antigens previously defined based on analysis of sera collected at the time of diagnosis.


METHODS
Proteins from human lung adenocarcinoma cell line A549 lysates were subjected to extensive fractionation. The resulting 1,824 fractions were spotted in duplicate on nitrocellulose-coated slides. The microarrays produced were used in a blinded validation study to determine whether annexin I, PGP9.5, and 14-3-3 theta antigens previously found to be targets of autoantibodies in newly diagnosed patients with lung cancer are associated with autoantibodies in sera collected at the presymptomatic stage and to determine whether additional antigens may be identified in prediagnostic sera. Individual sera collected from 85 patients within 1 year before a diagnosis of lung cancer and 85 matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were hybridized to individual microarrays.


RESULTS
We present evidence for the occurrence in lung cancer sera of autoantibodies to annexin I, 14-3-3 theta, and a novel lung cancer antigen, LAMR1, which precede onset of symptoms and diagnosis.


CONCLUSIONS
Our findings suggest potential utility of an approach to diagnosis of lung cancer before onset of symptoms that includes screening for autoantibodies to defined antigens.
Qiu
Ji
J
Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. jiqiu@fhcrc.org
Choi
Gina
G
Li
Lin
L
Wang
Hong
H
Pitteri
Sharon J
SJ
Pereira-Faca
Sandra R
SR
Krasnoselsky
Alexei L
AL
Randolph
Timothy W
TW
Omenn
Gilbert S
GS
Edelstein
Cim
C
Barnett
Matt J
MJ
Thornquist
Mark D
MD
Goodman
Gary E
GE
Brenner
Dean E
DE
Feng
Ziding
Z
Hanash
Samir M
SM
D048948:14-3-3 Proteins / Q000276:immunology*; D000230:Adenocarcinoma / Q000175:diagnosis / Q000276:immunology*; D017305:Annexin A1 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D042241:Early Diagnosis; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000276:immunology*; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D017474:Receptors, Laminin / Q000276:immunology; D015203:Reproducibility of Results; D012269:Ribosomal Proteins; D043222:Ubiquitin Thiolesterase / Q000276:immunology
D048948:14-3-3 Proteins; D017305:Annexin A1; D001323:Autoantibodies; C510624:RPSA protein, human; D017474:Receptors, Laminin; D012269:Ribosomal Proteins; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase
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