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Circulating levels of autoantibodies against L1-cell adhesion molecule as a potential diagnostic biomarker in esophageal squamous cell carcinoma

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Abstract

Background

Esophageal squamous cell carcinoma (ESCC) is a common malignant disease worldwide, especially in China. We aimed to determine the level of autoantibodies against L1CAM in patients with ESCC.

Methods

Levels of circulating autoantibodies against L1CAM antigens were determined by an enzyme-linked immunosorbent assay in cohort 1 (191 patients with ESCC and 94 normal controls) and validated in cohort 2 (47 patients with ESCC and 47 normal controls). Receiver-operating characteristics were employed to calculate diagnostic accuracy. Cumulative survival time was calculated by the Kaplan–Meier method and analyzed by the log-rank test.

Results

In cohorts 1 and 2, levels of autoantibodies against L1CAM were all significantly higher in sera of patients with ESCC compared to normal controls (P < 0.05). Detection of autoantibodies against L1CAM provided a sensitivity of 26.2%, a specificity of 90.4%, and an area under the curve (AUC) of 0.603 (95% CI 0.535–0.672) in diagnosing ESCC in cohort 1, and a sensitivity of 27.7%, a specificity of 91.5%, and an AUC of 0.628 (95% CI 0.516–0.741). Similar results were observed in the diagnosis of early stage ESCC (25.2% sensitivity, 90.4% specificity, and an AUC of 0.611 (95% CI 0.533–0.689) in cohort 1, and 33.3% sensitivity, 91.5% specificity, and an AUC of 0.636 (95% CI 0.439–0.832) in cohort 2). Moreover, positive rates of autoantibodies against L1CAM had no statistical correlation with clinical outcome of ESCC (P > 0.05).

Conclusions

Our results suggest that circulating autoantibodies against L1CAM is a potential biomarker for the early detection of ESCC.

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References

  1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108.

    Article  PubMed  Google Scholar 

  2. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–86.

    Article  CAS  PubMed  Google Scholar 

  3. Enzinger PC, Mayer RJ. Esophageal cancer. N Engl J Med. 2003;349(23):2241–52.

    Article  CAS  PubMed  Google Scholar 

  4. Pennathur A, Farkas A, Krasinskas AM, Ferson PF, Gooding WE, Gibson MK, Schuchert MJ, Landreneau RJ, Luketich JD. Esophagectomy for T1 esophageal cancer: outcomes in 100 patients and implications for endoscopic therapy. Ann Thorac Surg. 2009;87(4):1048–54 (discussion 1054–5).

  5. Shiku H, Takahashi T, Resnick LA, Oettgen HF, Old LJ. Cell surface antigens of human malignant melanoma. III. Recognition of autoantibodies with unusual characteristics. J Exp Med. 1977;145(3):784–9.

    Article  CAS  PubMed  Google Scholar 

  6. Wang X, Yu J, Sreekumar A, Varambally S, Shen R, Giacherio D, Mehra R, Montie JE, Pienta KJ, Sanda MG, Kantoff PW, Rubin MA, Wei JT, Ghosh D, Chinnaiyan AM. Autoantibody signatures in prostate cancer. N Engl J Med. 2005;353(12):1224–35.

    Article  CAS  PubMed  Google Scholar 

  7. Chapman C, Murray A, Chakrabarti J, Thorpe A, Woolston C, Sahin U, Barnes A, Robertson J. Autoantibodies in breast cancer: their use as an aid to early diagnosis. Ann Oncol. 2007;18(5):868–73.

    Article  CAS  PubMed  Google Scholar 

  8. Peng YH, Xu YW, Huang LS, Zhai TT, Dai LH, Qiu SQ, Yang YS, Chen WZ, Zhang LQ, Li EM, Xu LY. Autoantibody signatures combined with Epstein–Barr virus capsid antigen-IgA as a biomarker panel for the detection of nasopharyngeal carcinoma. Cancer Prev Res (Phila). 2015;8(8):729–36.

    Article  CAS  Google Scholar 

  9. Dai L, Tsay JC, Li J, Yie TA, Munger JS, Pass H, Rom WN, Zhang Y, Tan EM, Zhang JY. Autoantibodies against tumor-associated antigens in the early detection of lung cancer. Lung Cancer. 2016;99:172–9.

    Article  PubMed  Google Scholar 

  10. Felix K, Hauck O, Schnölzer M, Kempf T, Warnken U, Schneider K, Bergmann F, Fritz S, Werner J. Identification of novel serum autoantibodies for differential diagnosis of autoimmune pancreatitis and pancreatic ductal adenocarcinoma. Pancreas. 2016;45(9):1309–19.

    Article  CAS  PubMed  Google Scholar 

  11. Anderson KS, Cramer DW, Sibani S, Wallstrom G, Wong J, Park J, Qiu J, Vitonis A, LaBaer J. Autoantibody signature for the serologic detection of ovarian cancer. J Proteome Res. 2015;14(1):578–86.

    Article  CAS  PubMed  Google Scholar 

  12. Pedersen JW, Gentry-Maharaj A, Nøstdal A, Fourkala EO, Dawnay A, Burnell M, Zaikin A, Burchell J, Papadimitriou JT, Clausen H, Jacobs I, Menon U, Wandall HH. Cancer-associated autoantibodies to MUC1 and MUC4–a blinded case–control study of colorectal cancer in UK collaborative trial of ovarian cancer screening. Int J Cancer. 2014;134(9):2180–8.

    Article  CAS  PubMed  Google Scholar 

  13. Qiu J, Choi G, Li L, Wang H, Pitteri SJ, Pereira-Faca SR, Krasnoselsky AL, Randolph TW, Omenn GS, Edelstein C, Barnett MJ, Thornquist MD, Goodman GE, Brenner DE, Feng Z, Hanash SM. Occurrence of autoantibodies to annexin I, 14-3-3 theta and LAMR1 in prediagnostic lung cancer sera. J Clin Oncol. 2008;26(31):5060–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Peng YH, Xu YW, Guo H, Huang LS, Tan HZ, Hong CQ, Li SS, Xu LY, Li EM. Combined detection of serum Dickkopf-1 and its autoantibodies to diagnose esophageal squamous cell carcinoma. Cancer Med. 2016;5(7):1388–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xu YW, Peng YH, Chen B, Wu ZY, Wu JY, Shen JH, Zheng CP, Wang SH, Guo HP, Li EM, Xu LY. Autoantibodies as potential biomarkers for the early detection of esophageal squamous cell carcinoma. Am J Gastroenterol. 2014;109(1):36–45.

    Article  CAS  PubMed  Google Scholar 

  16. Desmetz C, Mange A, Maudelonde T, Solassol J. Autoantibody signatures: progress and perspectives for early cancer detection. J Cell Mol Med. 2011;15(10):2013–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chai Y, Peng B, Dai L, Qian W, Zhang Y, Zhang JY. Autoantibodies response to MDM2 and p53 in the immunodiagnosis of esophageal squamous cell carcinoma. Scand J Immunol. 2014;80(5):362–8.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang HF, Qin JJ, Ren PF, Shi JX, Xia JF, Ye H, Wang P, Song CH, Wang KJ, Zhang JY. A panel of autoantibodies against multiple tumor-associated antigens in the immunodiagnosis of esophageal squamous cell cancer. Cancer Immunol Immunother. 2016;65(10):1233–42.

    Article  CAS  PubMed  Google Scholar 

  19. Caron M, Choquet-Kastylevsky G, Joubert-Caron R. Cancer immunomics using autoantibody signatures for biomarker discovery. Mol Cell Proteomics. 2007;6(7):1115–22.

    Article  CAS  PubMed  Google Scholar 

  20. Tan HT, Low J, Lim SG, Chung MC. Serum autoantibodies as biomarkers for early cancer detection. FEBS J. 2009;276(23):6880–904.

    Article  CAS  PubMed  Google Scholar 

  21. Anderson KS, LaBaer J. The sentinel within: exploiting the immune system for cancer biomarkers. J Proteome Res. 2005;4(4):1123–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Moos M, Tacke R, Scherer H, Teplow D, Früh K, Schachner M. Neural adhesion molecule L1 as a member of the immunoglobulin superfamily with binding domains similar to fibronectin. Nature. 1988;334(6184):701–3.

    Article  CAS  PubMed  Google Scholar 

  23. Raveh S, Gavert N, Ben-Ze’ev A. L1 cell adhesion molecule (L1CAM) in invasive tumors. Cancer Lett. 2009;282(2):137–45.

    Article  CAS  PubMed  Google Scholar 

  24. Chen MM, Lee CY, Leland HA, Silletti S. Modification of the L1-CAM carboxy-terminus in pancreatic adenocarcinoma cells. Tumour Biol. 2011;32(2):347–57.

    Article  CAS  PubMed  Google Scholar 

  25. Rice TW, Blackstone EH, Rusch VW. 7th edition of the AJCC Cancer Staging Manual: esophagus and esophagogastric junction. Ann Surg Oncol. 2010;17:1721–4.

    Article  PubMed  Google Scholar 

  26. Rathjen FG, Schachner M. Immunocytological and biochemical characterization of a new neuronal cell surface component (L1 antigen) which is involved in cell adhesion. EMBO J. 1984;3(1):1–10.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fogel M, Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Smirnov A, Edler L, Ben-Arie A, Huszar M, Altevogt P. L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas. Lancet. 2003;362(9387):869–75.

    Article  CAS  PubMed  Google Scholar 

  28. Allory Y, Matsuoka Y, Bazille C, Christensen EI, Ronco P, Debiec H. The L1 cell adhesion molecule is induced in renal cancer cells and correlates with metastasis in clear cell carcinomas. Clin Cancer Res. 2005;11(3):1190–7.

    CAS  PubMed  Google Scholar 

  29. Boo YJ, Park JM, Kim J, Chae YS, Min BW, Um JW, Moon HY. L1 expression as a marker for poor prognosis, tumor progression, and short survival in patients with colorectal cancer. Ann Surg Oncol. 2007;14(5):1703–11.

    Article  PubMed  Google Scholar 

  30. Tischler V, Pfeifer M, Hausladen S, Schirmer U, Bonde AK, Kristiansen G, Sos ML, Weder W, Moch H, Altevogt P, Soltermann A. L1CAM protein expression is associated with poor prognosis in non-small cell lung cancer. Mol Cancer. 2011;10:127.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang YY, Li L, Zhao ZS, Wang YX, Ye ZY, Tao HQ. L1 and epithelial cell adhesion molecules associated with gastric cancer progression and prognosis in examination of specimens from 601 patients. J Exp Clin Cancer Res. 2013;32:66.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Kiefel H, Bondong S, Hazin J, Ridinger J, Schirmer U, Riedle S, Altevogt P. L1CAM: a major driver for tumor cell invasion and motility. Cell Adhes Migr. 2012;6(4):374–84.

    Article  Google Scholar 

  33. Zander H, Rawnaq T, von Wedemeyer M, Tachezy M, Kunkel M, Wolters G, Bockhorn M, Schachner M, Izbicki JR, Kaifi J. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients. BMC Cancer. 2011;11:189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Bondong S, Kiefel H, Hielscher T, Zeimet AG, Zeillinger R, Pils D, Schuster E, Castillo-Tong DC, Cadron I, Vergote I, Braicu I, Sehouli J, Mahner S, Fogel M, Altevogt P. Prognostic significance of L1CAM in ovarian cancer and its role in constitutive NF-κB activation. Ann Oncol. 2012;23(7):1795–802.

    Article  CAS  PubMed  Google Scholar 

  35. Zhou SL, Yue WB, Fan ZM, Du F, Liu BC, Li B, Han XN, Ku JW, Zhao XK, Zhang P, Cui J, Zhou FY, Zhang LQ, Fan XP, Zhou YF, Zhu LL, Liu HY, Wang LD. Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma. Dis Esophagus. 2014;27(8):790–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China-Guangdong Joint Fund (No. U1301227); the National Natural Science Foundation of China (Nos. 81472342, 81172264, 81472613); the Science and Technology Program of Guangdong (2013B060300020, 2014A030304060); the Innovative and Strong School Project of Guangdong (2015KQNCX044); the Shantou University Medical College Clinical Research Enhancement Initiative (201428); the Fok Ying-Tong Education Foundation (No. 141034); and the Li Kashing Foundation.

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    Authors and Affiliations

    1. Department of Clinical Laboratory Medicine, The Cancer Hospital of Shantou University Medical College, Shantou, China

      Y.-W. Xu & Y.-H. Peng

    2. The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou, China

      Y.-W. Xu, Y.-H. Peng, E.-M. Li & J.-J. Xie

    3. Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou, China

      L.-Q. Ran, E.-M. Li & J.-J. Xie

    4. Department of Radiation Oncology, The Cancer Hospital of Shantou University Medical College, Shantou, China

      T.-T. Zhai

    5. Department of Head and Neck Surgery, The Cancer Hospital of Shantou University Medical College, Shantou, China

      H.-P. Guo

    6. The Breast Center, The Cancer Hospital of Shantou University Medical College, Shantou, China

      S.-Q. Qiu

    7. Department of Surgical Oncology, Shantou Central Hospital, Shantou, China

      H.-L. Chen & Z.-Y. Wu

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    Y.-W. Xu, Y.-H. Peng, and L.-Q. Ran contributed equally to this work.

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    Xu, YW., Peng, YH., Ran, LQ. et al. Circulating levels of autoantibodies against L1-cell adhesion molecule as a potential diagnostic biomarker in esophageal squamous cell carcinoma. Clin Transl Oncol 19, 898–906 (2017). https://doi.org/10.1007/s12094-017-1623-4

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    • DOI: https://doi.org/10.1007/s12094-017-1623-4

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