Identification of 14-3-3θ as an antigen that induces a humoral response in lung cancer

Sandra R. Pereira-Faca, Rork Kuick, Eric Puravs, Qing Zhang, Alexei L. Krasnoselsky, Douglas Phanstiel, Ji Qiu, David E. Misek, Robert Hinderer, Martin Tammemagi, Maria Teresa Landi, Neil Caporaso, Ruth Pfeiffer, Cim Edelstein, Gary Goodman, Matt Barnett, Mark Thornquist, Dean Brenner, Samir M. Hanash

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

We have implemented a strategy to identify tumor antigens that induce a humoral immune response in lung cancer based on the analysis of tumor cell proteins. Chromatographically fractionated protein extracts from three lung cancer cell lines were subjected to Western blotting and hybridization with individual sera to determine serum antibody binding. Two sets of sera were initially investigated. One set consisted of sera from 19 newly diagnosed subjects with lung adenocarcinoma and 19 matched controls. A second independent set consisted of sera from 26 newly diagnosed subjects with lung adenocarcinoma and 24 controls matched for age, gender, and smoking history. One protein that exhibited significant reactivity with both sets of cancer sera (P = 0.0008) was confidently identified by mass spectrometry as 14-3-3θ. Remarkably, significant autoantibody reactivity against 14-3-3θ was also observed in an analysis of a third set consisting of 18 prediagnostic lung cancer sera collected as part of the Beta-Carotene and Retinol Efficacy Trial cohort study, relative to 19 matched controls (P = 0.0042). A receiver operating characteristic curve constructed with a panel of three proteins consisting of 14-3-3θ identified in this study, plus annexin 1 and protein gene product 9.5 proteins previously identified as associated with autoantibodies in lung cancer, gave a sensitivity of 55% at 95% specificity (area under the curve, 0.838) in discriminating lung cancer at the preclinical stage from matched controls.

Original languageEnglish (US)
Pages (from-to)12000-12006
Number of pages7
JournalCancer Research
Volume67
Issue number24
DOIs
StatePublished - Dec 15 2007
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Pereira-Faca, S. R., Kuick, R., Puravs, E., Zhang, Q., Krasnoselsky, A. L., Phanstiel, D., Qiu, J., Misek, D. E., Hinderer, R., Tammemagi, M., Landi, M. T., Caporaso, N., Pfeiffer, R., Edelstein, C., Goodman, G., Barnett, M., Thornquist, M., Brenner, D., & Hanash, S. M. (2007). Identification of 14-3-3θ as an antigen that induces a humoral response in lung cancer. Cancer Research, 67(24), 12000-12006. https://doi.org/10.1158/0008-5472.CAN-07-2913