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Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients

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Tumor Biology

Abstract

The aim of this study was to assess the prognostic value of EpCAM/MUC1 mRNA-positive circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). The presence of EpCAM/MUC1 mRNA-positive CTCs was evaluated in 74 NSCLC patients before the initiation of any therapy, from which 61 patients with surgical resection of tumor were also evaluable for EpCAM/MUC1 mRNA-positive CTC analysis after surgery, by quantitative real-time PCR assay. Sixty patients with benign lung disease (BLD) entered this study as controls. The results showed that blood levels of EpCAM and MUC1 mRNA in NSCLC patients before and after surgery were significantly higher than those in BLD patients (P = 0.001 and P = 0.015, respectively, for EpCAM; P = 0.003 and P = 0.026, respectively, for MUC1), and the levels of the two gene mRNA in NSCLC patients significantly decreased after surgery (P = 0.025 and P = 0.033, respectively). Disease recurrence significantly increased in NSCLC patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.004 and P = 0.001, respectively). Disease-free survival and overall survival significantly reduced in patients with EpCAM/MUC1 mRNA-positive CTC preoperation and postoperation (P = 0.012 and P = 0.002, respectively, for preoperation; both P < 0.001 for postoperation). Multivariate analysis demonstrated that the presence of EpCAM/MUC1 mRNA-positive CTCs before and after surgery was an independent factor associated with disease recurrence. In conclusion, the detection of EpCAM/MUC1 mRNA-positive CTCs in the blood before and after surgery is useful for predicting a poor prognosis in NSCLC patients who undergo curative surgery.

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References

  1. Brundage MD, Devies D, Mackillop WJ. Prognostic factors in non-small cell lung cancer. Chest. 2002;122:1037–57.

    Article  PubMed  Google Scholar 

  2. Asamura H, Goya T, Koshiishi Y, et al. A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancer. J Thorac Oncol. 2008;3:46–52.

    Article  PubMed  Google Scholar 

  3. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol. 2001;2:533–43.

    Article  CAS  PubMed  Google Scholar 

  4. Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6:339–51.

    Article  CAS  PubMed  Google Scholar 

  5. Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–40.

    Article  CAS  PubMed  Google Scholar 

  6. Lu J, Fan T, Zhao Q, et al. Isolation of circulating epithelial and tumor progenitor cells with an invasive phenotype from breast cancer patients. Int J Cancer. 2010;126:669–83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Ross JS, Slodkowska EA. Circulating and disseminated tumour cells in the management of breast cancer. Am J Clin Pathol. 2009;132:237–45.

    Article  CAS  PubMed  Google Scholar 

  8. Ring AE, Zabaglo L, Ormerod MG, Smith IE, Dowsett M. Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques. Br J Cancer. 2005;92:906–12.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Xenidis N, Ignatiadis M, Apostolaki S, et al. Cytokeratin-19 mRNA-positive circulating tumor cells after adjuvant chemotherapy in patients with early breast cancer. J Clin Oncol. 2009;27:2177–84.

    Article  CAS  PubMed  Google Scholar 

  10. Alix-Panabieres C, Sabine Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Cin Caner Res. 2008;14:5013–21.

    CAS  Google Scholar 

  11. Baeuerle PA, Gires O. EpCAM (CD326) finding its role in cancer. Br J Cancer. 2007;96:417–23.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Went PTH, Lugli A, Meier S, et al. Frequent EpCAM protein expression in human carcinomas. Hum Pathol. 2004;35:122–8.

    Article  CAS  PubMed  Google Scholar 

  13. Went P, Dirnhofer S, Schöpf D, et al. Expression and prognostic significance of EpCAM. J Cancer Mol. 2008;3:169–74.

    CAS  Google Scholar 

  14. Rao CG, Chianese D, Doyle GV, et al. Expression of epithelial cell adhesion molecule in carcinoma cells present in blood and primary and metastatic tumors. Int J Oncol. 2005;27:49–57.

    CAS  PubMed  Google Scholar 

  15. Kufe DW. Mucins in cancer: function, prognosis and therapy. Nat Rev Cancer. 2009;9:874–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4:45–60.

    Article  CAS  PubMed  Google Scholar 

  17. Nagai S, Takenaka K, Sonobe M, Eiji O, Hiromi W, Fumihiro T. A novel classification of MUC1 expression is correlated with tumor differentiation and postoperative prognosis in non-small cell lung cancer. J Thorac Oncol. 2006;1:46–51.

    Article  PubMed  Google Scholar 

  18. Tsutsumida H, Goto M, Kitajima S, Kubota I, Hirotsu Y, Yonezawa S. Combined status of MUC1 mucin and surfactant apoprotein A expression can predict the outcome of patients with small-size lung adenocarcinoma. Histopathology. 2004;44:147–55.

    Article  CAS  PubMed  Google Scholar 

  19. Ohgami A, Tsuda T, Osak T, et al. MUC1 mucin mRNA expression in stage I lung adenocarcinoma and its association with early recurrence. Ann Thorac Surg. 1999;67:810–4.

    Article  CAS  PubMed  Google Scholar 

  20. Livak KJ, Schnittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods. 2001;25:402–8.

    Article  CAS  PubMed  Google Scholar 

  21. Sergeant G, Penninckx F, Topal B. Quantitative RT-PCR detection of colorectal tumor cells in peripheral blood—a systematic review. J Surg Res. 2008;150:144–52.

    Article  CAS  PubMed  Google Scholar 

  22. Xenidis N, Perraki M, Kafousi M, et al. Predictive and prognostic value of peripheral blood cytokeratin-19 mRNA-positive cells detected by real-time polymerase chain reaction in node-negative breast cancer patients. J Clin Oncol. 2006;24:3756–62.

    Article  CAS  PubMed  Google Scholar 

  23. Liu Z, Jiang M, Zhao J, Ju H. Circulating tumor cells in perioperative esophageal cancer patients: quantitative assay system and potential clinical utility. Clin Cancer Res. 2007;13:2992–7.

    Article  CAS  PubMed  Google Scholar 

  24. de Albuquerque A, Kubisch L, Stolzel U, et al. Prognostic and predictive value of circulating tumor cell analysis in colorectal cancer patients. J Transl Med. 2012;10:222–8.

    Article  PubMed Central  PubMed  Google Scholar 

  25. Tanaka F, Yoneda K, Kondo N, et al. Circulating tumor cell as a diagnostic marker in primary lung cancer. Clin Cancer Res. 2009;15:6980–6.

    Article  CAS  PubMed  Google Scholar 

  26. Yamashita J, Matsuo A, Kurusu Y, Saiahoji T, Hayashi N, Ogawa M. Preoperative evidence of circulating tumor cells by means of reverse transcriptase-polymerase chain reaction for carcinoembryonic antigen messenger RNA is a independent predictor of survival in non-small cell lung cancer: a prospective study. J Thorac Cardiovasc Surg. 2002;124:299–305.

    Article  CAS  PubMed  Google Scholar 

  27. Yie S-M, Lou B, Ye S-R, et al. Clinical significance of detecting survivin-expressing circulating cancer cell in patients with non-small cell lung cancer. Lung Cancer. 2009;63:284–90.

    Article  PubMed  Google Scholar 

  28. Yoon SO, Kim YT, Jung KC, Jeon YK, Kim BH, Kim CW. TTF-1 mRNA-positive circulating tumor cells in the peripheral blood predict poor prognosis in surgically resected non-small cell lung cancer patients. Lung Cancer. 2011;71:209–16.

    Article  PubMed  Google Scholar 

  29. Fidler IL. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.

    Article  CAS  PubMed  Google Scholar 

  30. O'Sullivan GC, Collins JK, Kelly J, Morgan J, Madden M, Shanahan F. Micrometastases: marker of metastatic potential or evidence or residual disease? Gut. 1997;40:512–5.

    PubMed  Google Scholar 

  31. Fehm T, Becker S, Becker-Pergola G, et al. Presence of apoptotic and nonapotptotic disseminated tumor cells reflects the response to neoadjuvant systemic therapy in breast cancer. Breast Cancer Res. 2006;8:R60.

    Article  PubMed Central  PubMed  Google Scholar 

  32. Zieglschmid V, Hollmann C, Bocher O. Detection of disseminated tumor cells in peripheral blood. Crit Rev Clin Lab Sci. 2005;42:155–96.

    Article  CAS  PubMed  Google Scholar 

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Zhu, WF., Li, J., Yu, LC. et al. Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients. Tumor Biol. 35, 1211–1219 (2014). https://doi.org/10.1007/s13277-013-1162-8

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  • DOI: https://doi.org/10.1007/s13277-013-1162-8

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