Tumor Biology

, Volume 34, Issue 3, pp 1813–1818

ADAM17 is overexpressed in non-small cell lung cancer and its expression correlates with poor patient survival

  • Shuang-Shuang Ni
  • Ji Zhang
  • Wei-Li Zhao
  • Xiao-Chun Dong
  • Jin-Lin Wang
Research Article


The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients’ survival rate was assessed by Kaplan–Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P = 0.026), tumor size (P = 0.001), clinical stage (P = 0.016), and lymph node metastases (P < 0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.


ADAM17 NSCLC Biomarker Prognosis 


  1. 1.
    Mascaux C, Iannino N, Martin B, Paesmans M, Berghmans T, Dusart M, et al. The role of RAS oncogene in survival of patients with lung cancer: a systematic review of the literature with meta-analysis. Br J Cancer. 2005;92:131–9. doi:10.1038/sj.bjc.6602258.PubMedCrossRefGoogle Scholar
  2. 2.
    Steels E, Paesmans M, Berghmans T, Branle F, Lemaitre F, Mascaux C, et al. Role of p53 as a prognostic factor for survival in lung cancer: a systematic review of the literature with a meta-analysis. Eur Respir J. 2001;18:705–19.PubMedCrossRefGoogle Scholar
  3. 3.
    Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med. 2007;356:800–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Xu P, Derynck R. Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. Mol Cell. 2010;37:551–66. doi:10.1016/j.molcel.2010.01.034.PubMedCrossRefGoogle Scholar
  5. 5.
    Kenny PA, Bissell MJ. Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest. 2007;117:337–45. doi:10.1172/JCI29518.PubMedCrossRefGoogle Scholar
  6. 6.
    Bozkulak EC, Weinmaster G. Selective use of ADAM10 and ADAM17 in activation of Notch1 signaling. Mol Cell Biol. 2009;29:5679–95. doi:10.1128/MCB.00406-09.PubMedCrossRefGoogle Scholar
  7. 7.
    Szalad A, Katakowski M, Zheng X, Jiang F, Chopp M. Transcription factor Sp1 induces ADAM17 and contributes to tumor cell invasiveness under hypoxia. J Exp Clin Cancer Res. 2009;28:129. doi:10.1186/1756-9966-28-129.PubMedCrossRefGoogle Scholar
  8. 8.
    Yoshimura T, Tomita T, Dixon MF, Axon AT, Robinson PA, Crabtree JE. ADAMs (a disintegrin and metalloproteinase) messenger RNA expression in Helicobacter pylori-infected, normal, and neoplastic gastric mucosa. J Infect Dis. 2002;185:332–40.PubMedCrossRefGoogle Scholar
  9. 9.
    Yasuda H, Hirata S, Inoue K, Mashima H, Ohnishi H, Yoshiba M. Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. Biochem Biophys Res Commun. 2007;354:154–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Ebi M, Kataoka H, Shimura T, Kubota E, Hirata Y, Mizushima T, et al. TGFβ induces proHB-EGF shedding and EGFR transactivation through ADAM activation in gastric cancer cells. Biochem Biophys Res Commun. 2010;402:449–54. doi:10.1016/j.bbrc.2010.09.130.PubMedCrossRefGoogle Scholar
  11. 11.
    Baumgart A, Seidl S, Vlachou P, Michel L, Mitova N, Schatz N, et al. ADAM17 regulates epidermal growth factor receptor expression through the activation of Notch1 in non-small cell lung cancer. Cancer Res. 2010;70:5368–78. doi:10.1158/0008-5472.CAN-09-3763.PubMedCrossRefGoogle Scholar
  12. 12.
    Tu L, Liu Z, He X, He Y, Yang H, Jiang Q, et al. Over-expression of eukaryotic translation initiation factor 4 gamma 1 correlates with tumor progression and poor prognosis in nasopharyngeal carcinoma. Mol Cancer. 2010;9:78. doi:10.1186/1476-4598-9-78.PubMedCrossRefGoogle Scholar
  13. 13.
    Liu Z, Li L, Yang Z, Luo W, Li X, Yang H, et al. Increased expression of MMP9 is correlated with poor prognosis of nasopharyngeal carcinoma. BMC Cancer. 2010;10:270. doi:10.1186/1471-2407-10-270.PubMedCrossRefGoogle Scholar
  14. 14.
    Arribas J, Bech-Serra JJ, Santiago-Josefat B. ADAMs, cell migration and cancer. Cancer Metastasis Rev. 2006;25:57–68.PubMedCrossRefGoogle Scholar
  15. 15.
    Duffy MJ, McKiernan E, O'Donovan N, McGowan PM. The role of ADAMs in disease pathophysiology. Clin Chim Acta. 2009;403:31–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Scheller J, Chalaris A, Garbers C, Rose-John S. ADAM17: a molecular switch to control inflammation and tissue regeneration. Trends Immunol. 2011;32:380–7. doi:10.1016/j.it.2011.05.005.PubMedCrossRefGoogle Scholar
  17. 17.
    Willems SH, Tape CJ, Stanley PL, Taylor NA, Mills IG, Neal DE, et al. Thiol isomerases negatively regulate the cellular shedding activity of ADAM17. Biochem J. 2010;428:439–50. doi:10.1042/BJ20100179.PubMedCrossRefGoogle Scholar
  18. 18.
    Lin P, Sun X, Feng T, Zou H, Jiang Y, Liu Z, et al. ADAM17 regulates prostate cancer cell proliferation through mediating cell cycle progression by EGFR/PI3K/AKT pathway. Mol Cell Biochem. 2012;359:235–43. doi:10.1007/s11010-011-1018-8.PubMedCrossRefGoogle Scholar
  19. 19.
    Stokes A, Joutsa J, Ala-Aho R, Pitchers M, Pennington CJ, Martin C, et al. Expression profiles and clinical correlations of degradome components in the tumor microenvironment of head and neck squamous cell carcinoma. Clin Cancer Res. 2010;16:2022–35. doi:10.1158/1078-0432.CCR-09-2525.PubMedCrossRefGoogle Scholar
  20. 20.
    McGowan PM, Ryan BM, Hill AD, McDermott E, O'Higgins N, Duffy MJ. ADAM-17 expression in breast cancer correlates with variables of tumor progression. Clin Cancer Res. 2007;13:2335–43. doi:10.1158/1078-0432.CCR-06-2092.PubMedCrossRefGoogle Scholar
  21. 21.
    Saftig P, Reiss K. The "A Disintegrin And Metalloproteases" ADAM10 and ADAM17: novel drug targets with therapeutic potential? Eur J Cell Biol. 2011;90:527–35. doi:10.1016/j.ejcb.2010.11.005.PubMedCrossRefGoogle Scholar
  22. 22.
    Sinnathamby G, Zerfass J, Hafner J, Block P, Nickens Z, Hobeika A, et al. ADAM metallopeptidase domain 17 (ADAM17) is naturally processed through major histocompatibility complex (MHC) class I molecules and is a potential immunotherapeutic target in breast, ovarian and prostate cancers. Clin Exp Immunol. 2011;163:324–32. doi:10.1111/j.1365-2249.2010.04298.x.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Shuang-Shuang Ni
    • 1
  • Ji Zhang
    • 1
  • Wei-Li Zhao
    • 2
  • Xiao-Chun Dong
    • 2
  • Jin-Lin Wang
    • 1
  1. 1.Department of Radiology, Changzheng HospitalSecond Military Medical UniversityShanghaiChina
  2. 2.School of PharmacyFudan UniversityShanghaiChina

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