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Enhancement of a multianalyte serum biomarker panel to identify lymph node metastases in non‐small cell lung cancer with circulating autoantibody biomarkers
Author(s) -
Patel Kalpa,
Farlow Erin C.,
Kim Anthony W.,
Lee BaoShiang,
Basu Sanjib,
Coon John S.,
DeCresce David,
Thimothy Lida,
Walters Kelly A.,
Fhied Cristina,
Chang Christopher,
Chen SsuHsien,
Faber L. Penfield,
Bonomi Philip,
Liptay Michael J.,
Borgia Jeffrey A.
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25644
Subject(s) - autoantibody , medicine , biomarker , lung cancer , lymph node , cancer , cancer biomarkers , immunology , oncology , antibody , biology , biochemistry
We recently reported the development of a multianalyte serum algorithm to identify nodal status in non‐small cell lung cancer (NSCLC) patients facing an anatomic resection with curative intent. This study aims to enhance the overall performance characteristics of this test by adding autoantibody biomarkers identified through immunoproteomic discovery. More specifically, we used sera from 20 NSCLC patients to probe 2‐D immunoblots of HCC827 lysates for tumor‐associated autoantigens. Relevant differences in immunoreactivity associated with pathological nodal status were then identified via tandem mass spectrometry. Identified autoantigens were then developed into Luminex immunobead assays alongside a series of autoantigen targets relevant to early‐disease detection. These assays were then used to measure circulating autoantibody levels in the identical cohort of NSCLC patients used in our original study. This strategy identified 11 autoantigens found primarily in patients with disease progression to the locoregional lymph nodes. Custom Luminex‐based “direct‐capture” assays (25 total; including autoantibody targets relevant to early‐disease detection) were assembled to measure autoantibody levels in sera from 107 NSCLC patients. Multivariate classification algorithms were then used to identify the optimal combination of biomarkers when considered collectively with our original 6‐analyte serum panel. The new algorithm resulting from this analysis consists of TNF‐α, TNF‐RI, MIP‐1α and autoantibodies against Ubiquilin‐1, hydroxysteroid‐(17‐β)‐dehydrogenase, and triosephosphate isomerase. The inclusion of autoantibody biomarkers provided a dramatic improvement in the overall test performance characteristics, relative to the original test panel, including an 11% improvement in the classification efficiency.