Toward an early diagnosis of lung cancer: An autoantibody signature for squamous cell lung carcinoma

Abstract

Serum-based diagnosis offers the prospect of early lung carcinoma detection and of differentiation between benign and malignant nodules identified by CT. One major challenge toward a future blood-based diagnostic consists in showing that seroreactivity patterns allow for discriminating lung cancer patients not only from normal controls but also from patients with non-tumor lung pathologies. We addressed this question for squamous cell lung cancer, one of the most common lung tumor types. Using a panel of 82 phage-peptide clones, which express potential autoantigens, we performed serological spot assay. We screened 108 sera, including 39 sera from squamous cell lung cancer patients, 29 sera from patients with other non-tumor lung pathologies, and 40 sera from volunteers without known disease. To classify the serum groups, we employed the standard Na€ ıve Bayesian method combined with a subset selection approach. We were able to separate squamous cell lung carcinoma and normal sera with an accuracy of 93%. Low-grade squamous cell lung carcinoma were separated from normal sera with an accuracy of 92.9%. We were able to distinguish squamous cell lung carcinoma from non-tumor lung pathologies with an accuracy of 83%. Three phage-peptide clones with sequence homology to ROCK1, PRKCB1 and KIAA0376 reacted with more than 15% of the cancer sera, but neither with normal nor with non-tumor lung pathology sera. Our study demonstrates that seroreactivity profiles combined with statistical classification methods have great potential for discriminating patients with squamous cell lung carcinoma not only from normal controls but also from patients with non-tumor lung pathologies.

Immune Responses Are Characterized by Specific Shared Immunoglobulin Peptides That Can Be Detected by Proteomic Techniques*

“…While immunoglobulins were used before to find antigens for biomarker use, the use of the immunoglobulin sequences themselves as markers for a disease would be a novel method (10). Auto-immune diseases could be well-suited for such an approach, but also cancer is known to result in an antibody response (11,12). Thus, specific antibody sequences could be of diagnostic and prognostic use in such diseases.…”

Autoanticorps et diagnostic précoce des cancers

“…Enfin, des travaux récents ont utilisé une banque d'expression d'ADN complémentaire pour identifier six peptides immunogènes. Ceux-ci ont été proposés comme signature humorale et ont permis de distinguer les patients atteints de cancers (n  90) de ceux qui n'étaient pas atteints (n  90) et des patients bronchitiques chroniques (n  30) avec une sensibilité et une spécificité élevées (93 %) [19]. Ainsi, cette signature humorale basée sur l'étude de la fréquence d'apparition d'un panel d'anticorps est une approche prometteuse pour le diagnostic des formes précoces de cancer.…”

Autoantibodies to chromogranin A are potential diagnostic biomarkers for non-small cell lung cancer

“…The overexpression, mutation, misfolding, and aberrant degradation of these selfproteins appear to induce autoreactive immune responses in cancer patients [12]. Indeed, autoantibodies against autologous TAAs have been detected in the peripheral blood, and their early diagnostic value has been recognized [13][14][15]. These novel tumor-associated autoantibodies (AAbs) provide new ideas for the early diagnosis and therapy of tumors.…”

“…According to GLOBOCAN 2012, it is the leading cause of cancer morbidity (1.8 million, 13.0 % of the total) and mortality (1.6 million, 19.4 % of the total) worldwide [1]. Non-small cell lung cancer (NSCLC) accounts for about 80% of lung cancer cases and shows neuroendocrine differentiation features relating to chromogranin A (ChgA) [2][3][4].…”