Circulating tumor-associated autoantibody signatures for diagnosis and prognosis in small-cell lung cancer and lung adenocarcinoma

BACKGROUND: Tumour-associated autoantibodies (TAAbs) are promising biomarkers for cancer detection, but their induction and clinical relevance in lung cancer remain unclear. METHODS: Serum samples from 695 individuals were analysed for TAAb profiling by protein-array screening and two-stage ELISA validation. Diagnostic models were constructed with identified TAAbs and compared with conventional tumour markers. Potential mechanisms, clinical and prognostic features of TAAb seropositivity were analysed and its presence in prediagnostic sera was evaluated to assess the potential for early detection. RESULTS: Six TAAbs for small cell lung cancer (SCLC) and four for lung adenocarcinoma (LUAD) were identified, demonstrating excellent diagnostic performance (AUC > 0.8) and outperforming ProGRP and CEA. TAAb induction correlated with antigen overexpression, somatic mutations and HLA class II amino acid polymorphisms. TAAb panel seropositivity was associated with older age and advanced stage in both subtypes, and predicted poor survival in SCLC but a favourable outcome in advanced LUAD. In prediagnostic sera, the TAAb concentration increased progressively, with detectability up to 2 years before clinical diagnosis. CONCLUSIONS: Distinct TAAb panels were identified for SCLC and LUAD, serving as accurate diagnostic markers that enable early detection and as indicators of prognosis in different clinical contexts.

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Publication Details

Journal
British Journal of Cancer
Published
2026-06-25
DOI
https://doi.org/10.1038/s41416-026-03504-z
Primary Topic
Lung Cancer Research Studies
Type
article
Field-Weighted Citation Impact
0.00

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article

Circulating tumor-associated autoantibody signatures for diagnosis and prognosis in small-cell lung cancer and lung adenocarcinoma

Kaori Muto, C B Liu, Yuji Yamanashi, Yasunobu Nagata et al.
British Journal of Cancer
Lung Cancer Research Studies
article

Circulating tumor-associated autoantibody signatures for diagnosis and prognosis in small-cell lung cancer and lung adenocarcinoma

Kaori Muto, C B Liu, Yuji Yamanashi, Yasunobu Nagata, Yoichi Furukawa, Natsuhiko Kumasaka, Shigeo Murayama, Kozo Yoshimori, Yoichiro Kamatani, Yukinori Okada, Wataru Obara, Yoji Sagiya, Yasuo Takahashi, Eriko Fukuda, Naoki Goshima, Takayuki Morisaki, Y NAKAMURA, Koichi Matsuda, Akinori Kanai, Chikako Nito, Chizu Tanikawa, Masahiko Higashiyama, Yoshinori Murakami, Satoshi Wakita, Yoshio Miki, Yuka Okamoto, Yoshinobu Koga, Yu-Ki Iwasaki, Akihide Masumoto, The Biobank Japan Project, Ken Yamaji, Hiroki Yamaguchi, Yutaka Suzuki, Satoshi Asai, Daisuke Obata, Kazuhisa Takahashi, Yukihiro Koretsune, Shuzo Kobayashi, Akiko Nagai, Hiromi Tsuru, Shinichi Higashiue
article en

Abstract

BACKGROUND: Tumour-associated autoantibodies (TAAbs) are promising biomarkers for cancer detection, but their induction and clinical relevance in lung cancer remain unclear. METHODS: Serum samples from 695 individuals were analysed for TAAb profiling by protein-array screening and two-stage ELISA validation. Diagnostic models were constructed with identified TAAbs and compared with conventional tumour markers. Potential mechanisms, clinical and prognostic features of TAAb seropositivity were analysed and its presence in prediagnostic sera was evaluated to assess the potential for early detection. RESULTS: Six TAAbs for small cell lung cancer (SCLC) and four for lung adenocarcinoma (LUAD) were identified, demonstrating excellent diagnostic performance (AUC > 0.8) and outperforming ProGRP and CEA. TAAb induction correlated with antigen overexpression, somatic mutations and HLA class II amino acid polymorphisms. TAAb panel seropositivity was associated with older age and advanced stage in both subtypes, and predicted poor survival in SCLC but a favourable outcome in advanced LUAD. In prediagnostic sera, the TAAb concentration increased progressively, with detectability up to 2 years before clinical diagnosis. CONCLUSIONS: Distinct TAAb panels were identified for SCLC and LUAD, serving as accurate diagnostic markers that enable early detection and as indicators of prognosis in different clinical contexts.

British Journal of Cancer
Nihon University (JP), Tokyo Medical University (JP), Shiga University of Medical Science (JP), Iwate Medical University (JP), Juntendo University (JP), Osaka National Hospital (JP), Fukuoka Tokushukai Hospital (JP), Japan Anti Tuberculosis Association (JP), The Cancer Institute Hospital (JP), Aso Iizuka Hospital (JP), RIKEN Center for Integrative Medical Sciences (JP), Osaka International Cancer Institute (JP), Tokyo Metropolitan Geriatric Hospital (JP), Fukujuji Hospital (JP), Japanese Foundation For Cancer Research (JP), National Institute of Advanced Industrial Science and Technology (JP), The University of Tokyo (JP), Nippon Medical School (JP), The University of Osaka (JP)
Takeda Science Foundation, Japan Agency for Medical Research and Development, National Institute of Advanced Industrial Science and Technology, Ministry of Education, Culture, Sports, Science and Technology, University of Tokyo, Institute of Medical Science, University of Tokyo
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Openalex Percentile: Top 8%
Lung Cancer Research Studies
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