Development of a multiplexed tumor-associated autoantibody-based blood test for the detection of non-small cell lung cancer.
OBJECTIVE
Non-small cell lung cancer (NSCLC) has an overall 5-year survival of <15%; however, the 5-year survival for stage I disease is over 50%. Unfortunately, 75% of NSCLC is diagnosed at an advanced stage not amenable to surgery. A convenient serum assay capable of unambiguously identifying patients with NSCLC may provide an ideal diagnostic measure to complement computed tomography-based screening protocols.


METHODS
Standard immunoproteomic method was used to assess differences in circulating autoantibodies among lung adenocarcinoma patients relative to cancer-free controls. Candidate autoantibodies identified by these discovery phase studies were translated into Luminex-based "direct-capture" immunobead assays along with 10 autoantigens with previously reported diagnostic value. These assays were then used to evaluate a second patient cohort composed of four discrete populations, including: 117 NSCLC (81 T(1-2)N(0)M(0) and 36 T(1-2)N(1-2)M(0)), 30 chronic obstructive pulmonary disorder (COPD)/asthma, 13 nonmalignant lung nodule, and 31 "normal" controls. Multivariate statistical methods were then used to identify the optimal combination of biomarkers for classifying patient disease status and develop a convenient algorithm for this purpose.


RESULTS
Our immunoproteomic-based biomarker discovery efforts yielded 16 autoantibodies differentially expressed in NSCLC versus control serum. Thirteen of the 25 analytes tested showed statistical significance (Mann-Whitney P < 0.05 and a receiver operator characteristic "area under the curve" over 0.65) when evaluated against a second patient cohort. Multivariate statistical analyses identified a six-biomarker panel with only a 7% misclassification rate.


CONCLUSIONS
We developed a six-autoantibody algorithm for detecting cases of NSCLC among several high-risk populations. Population-based validation studies are now required to assign the true value of this tool for identifying early-stage NSCLC.
Farlow
Erin C
EC
Department of General Surgery, Rush University Medical Center, Chicago, Illinois 60612, USA.
Patel
Kalpa
K
Basu
Sanjib
S
Lee
Bao-Shiang
BS
Kim
Anthony W
AW
Coon
John S
JS
Faber
L Penfield
LP
Bonomi
Philip
P
Liptay
Michael J
MJ
Borgia
Jeffrey A
JA
D000230:Adenocarcinoma / Q000097:blood; D000465:Algorithms; D000912:Antibodies, Neoplasm / Q000032:analysis; D000951:Antigens, Neoplasm / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000276:immunology; D045744:Cell Line, Tumor; D055088:Early Detection of Cancer; D006403:Hematologic Tests; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000276:immunology; D040081:Protein Array Analysis; D040901:Proteomics
D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D001323:Autoantibodies