title: Enhancement of a multianalyte serum biomarker panel to identify lymph node metastases in non-small cell lung cancer with circulating autoantibody biomarkers.
abstract: 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.
authors.affiliation: Department of Biochemistry, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Kalpa
authors.initials: K
authors.lastname: Patel
authors.forename: Erin C
authors.initials: EC
authors.lastname: Farlow
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Kim
authors.forename: Bao-Shiang
authors.initials: BS
authors.lastname: Lee
authors.forename: Sanjib
authors.initials: S
authors.lastname: Basu
authors.forename: John S
authors.initials: JS
authors.lastname: Coon
authors.forename: David
authors.initials: D
authors.lastname: DeCresce
authors.forename: Lida
authors.initials: L
authors.lastname: Thimothy
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Walters
authors.forename: Cristina
authors.initials: C
authors.lastname: Fhied
authors.forename: Christopher
authors.initials: C
authors.lastname: Chang
authors.forename: Ssu-Hsien
authors.initials: SH
authors.lastname: Chen
authors.forename: L Penfield
authors.initials: LP
authors.lastname: Faber
authors.forename: Philip
authors.initials: P
authors.lastname: Bonomi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Liptay
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Borgia
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D001323:Autoantibodies / Q000097:blood*; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000276:immunology / Q000473:pathology; D015331:Cohort Studies; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D053719:Tandem Mass Spectrometry
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor