Skip to main content
Top
Published in: Tumor Biology 2/2014

01-02-2014 | Research Article

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

Authors: Wen-Fang Zhu, Jian Li, Li-Chao Yu, Yian Wu, Xin-Ping Tang, Yi-Ming Hu, Yong-Chang Chen

Published in: Tumor Biology | Issue 2/2014

Login to get access

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.
Literature
1.
go back to reference Brundage MD, Devies D, Mackillop WJ. Prognostic factors in non-small cell lung cancer. Chest. 2002;122:1037–57.PubMedCrossRef Brundage MD, Devies D, Mackillop WJ. Prognostic factors in non-small cell lung cancer. Chest. 2002;122:1037–57.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
4.
go back to reference Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6:339–51.PubMedCrossRef Pantel K, Alix-Panabieres C, Riethdorf S. Cancer micrometastases. Nat Rev Clin Oncol. 2009;6:339–51.PubMedCrossRef
5.
go back to reference Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–40.PubMedCrossRef Pantel K, Brakenhoff RH, Brandt B. Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer. 2008;8:329–40.PubMedCrossRef
6.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
7.
go back to reference Ross JS, Slodkowska EA. Circulating and disseminated tumour cells in the management of breast cancer. Am J Clin Pathol. 2009;132:237–45.PubMedCrossRef Ross JS, Slodkowska EA. Circulating and disseminated tumour cells in the management of breast cancer. Am J Clin Pathol. 2009;132:237–45.PubMedCrossRef
8.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
9.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
10.
go back to reference Alix-Panabieres C, Sabine Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Cin Caner Res. 2008;14:5013–21. Alix-Panabieres C, Sabine Riethdorf S, Pantel K. Circulating tumor cells and bone marrow micrometastasis. Cin Caner Res. 2008;14:5013–21.
12.
go back to reference Went PTH, Lugli A, Meier S, et al. Frequent EpCAM protein expression in human carcinomas. Hum Pathol. 2004;35:122–8.PubMedCrossRef Went PTH, Lugli A, Meier S, et al. Frequent EpCAM protein expression in human carcinomas. Hum Pathol. 2004;35:122–8.PubMedCrossRef
13.
go back to reference Went P, Dirnhofer S, Schöpf D, et al. Expression and prognostic significance of EpCAM. J Cancer Mol. 2008;3:169–74. Went P, Dirnhofer S, Schöpf D, et al. Expression and prognostic significance of EpCAM. J Cancer Mol. 2008;3:169–74.
14.
go back to reference 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.PubMed 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.PubMed
16.
go back to reference Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4:45–60.PubMedCrossRef Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4:45–60.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
19.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
28.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
29.
go back to reference Fidler IL. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.PubMedCrossRef Fidler IL. The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nat Rev Cancer. 2003;3:453–8.PubMedCrossRef
30.
go back to reference 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 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
31.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
32.
go back to reference Zieglschmid V, Hollmann C, Bocher O. Detection of disseminated tumor cells in peripheral blood. Crit Rev Clin Lab Sci. 2005;42:155–96.PubMedCrossRef Zieglschmid V, Hollmann C, Bocher O. Detection of disseminated tumor cells in peripheral blood. Crit Rev Clin Lab Sci. 2005;42:155–96.PubMedCrossRef
Metadata
Title
Prognostic value of EpCAM/MUC1 mRNA-positive cells in non-small cell lung cancer patients
Authors
Wen-Fang Zhu
Jian Li
Li-Chao Yu
Yian Wu
Xin-Ping Tang
Yi-Ming Hu
Yong-Chang Chen
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 2/2014
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-013-1162-8

Other articles of this Issue 2/2014

Tumor Biology 2/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine