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Background <p>Tumour-associated autoantibodies (TAAbs) are promising biomarkers for cancer detection, but their induction and clinical relevance in lung cancer remain unclear.</p> Methods <p>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.</p> Results <p>Six TAAbs for small cell lung cancer (SCLC) and four for lung adenocarcinoma (LUAD) were identified, demonstrating excellent diagnostic performance (AUC &gt; 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月25日

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

摘要

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.