ADAM28 is a serological and histochemical marker for non-small-cell lung cancers

Hiroaki Kuroda, Satsuki Mochizuki, Masayuki Shimoda, Miyuki Chijiiwa, Kazunori Kamiya, Yotaro Izumi, Masazumi Watanabe, Hirohisa Horinouchi, Masahumi Kawamura, Koichi Kobayashi, Yasunori Okada

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Abstract

ADAM28 (a disintegrin and metalloproteinase 28) is over-expressed in non-small-cell lung cancer (NSCLC) with correlation to cancer cell proliferation, tumor size and lymph node metastasis. The present study was aimed to develop an enzyme-linked immunosorbent assay (ELISA) system for diagnosis and monitoring of NSCLC. Our ELISA specifically measured ADAM28, showing negligible cross-reactivity with other metalloproteinases. The ADAM28 level in the NSCLC tissue was remarkably 36.9-fold higher than that in the non-neoplastic lung tissue (p < 0.001). The serum level was significantly 4.6-fold higher in the NSCLC patients (5.41 8.62 ng/ml; n = 102) than in the control subjects (1.17 0.93 ng/ml; n = 20) (p < 0.001), and increased with progress of tumor stage (p < 0.001). The level was also significantly higher in the patients with recurrent carcinoma than the control (p < 0.001) and in the patients with lymph node metastasis than those without metastasis (p < 0.001). The sensitivity, false-negative rate and AUC for ADAM28 were better than those for carcinoembryonic antigen. The combination of both assays improved the sensitivity, specificity, false-positive and false-negative rates for NSCLC. There was a positive correlation between the ADAM28 level measured by ELISA system and the degree of immunostaining in the lung adenocarcinomas with a size of &20 mm in diameter. The adenocarcinoma patients showing the high immunohistochemical reaction exhibited a poorer disease-free survival than those with the lower immunoreactivity (n = 102; p < 0.05). These data demonstrate that our ELISA is specific and sensitive to monitor the levels of ADAM28 in the samples from NSCLC patients and suggest that ADAM28 is a useful serological and histochemical marker for NSCLC.

Original languageEnglish
Pages (from-to)1844-1856
Number of pages13
JournalInternational Journal of Cancer
Volume127
Issue number8
DOIs
Publication statusPublished - 2010 Oct 15

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Keywords

  • ADAM
  • biological marker
  • diagnosis
  • lung cancer
  • prognosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Kuroda, H., Mochizuki, S., Shimoda, M., Chijiiwa, M., Kamiya, K., Izumi, Y., Watanabe, M., Horinouchi, H., Kawamura, M., Kobayashi, K., & Okada, Y. (2010). ADAM28 is a serological and histochemical marker for non-small-cell lung cancers. International Journal of Cancer, 127(8), 1844-1856. https://doi.org/10.1002/ijc.25212