Immunobiomarkers in small cell lung cancer: potential early cancer signals.
OBJECTIVE
We investigated the presence of autoantibodies as immunobiomarkers to a panel of tumor-associated antigens in a group of individuals with small cell lung cancer (SCLC), a disease group that has a poor overall cancer prognosis and therefore may benefit most from early diagnosis.


METHODS
Sera from 243 patients with confirmed SCLC and normal controls matched for age, sex, and smoking history were analyzed for the presence of these early immunobiomarkers (i.e., autoantibodies to p53, CAGE, NY-ESO-1, GBU4-5, Annexin I, SOX2, and Hu-D) by ELISA.


RESULTS
Autoantibodies were seen to at least 1 of 6 antigens in 55% of all the SCLC patients' sera tested, with a specificity of 90% compared with controls. Using a higher assay cutoff to achieve a specificity of 99%, autoantibodies were still detectable in 42% of SCLC patients (receiver operator characteristic area under the curve = 0.76). There was no significant difference in sensitivity when analyzed by stage of the cancer or by patient age or gender. The frequency of autoantibodies to individual antigens varied, ranging from 4% for GBU4-5 to 35% for SOX2. Levels of Annexin I autoantibodies were not elevated in patients with SCLC. Antibodies were also detected in 4 separate patients whose sera were taken up to 3 months before tumor diagnosis.


CONCLUSIONS
The presence of an autoantibody to one or more cancer-associated antigens may provide an important addition to the armamentarium available to the clinician to aid early detection of SCLC in high-risk individuals.
Division of Surgery, University of Nottingham, Nottingham, United Kingdom. caroline.chapman@nottingham.ac.uk
Caroline J
CJ
Chapman
Alison J
AJ
Thorpe
Andrea
A
Murray
Celine B
CB
Parsy-Kowalska
Jared
J
Allen
Kelly M
KM
Stafford
Alok S
AS
Chauhan
Thomas A
TA
Kite
Paul
P
Maddison
John F R
JF
Robertson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000737:chemistry; D014408:Biomarkers, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012306:Risk; D055752:Small Cell Lung Carcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*
D001323:Autoantibodies; D014408:Biomarkers, Tumor