Circulating Tumor Cells Identify Early Recurrence in Patients with Non-Small Cell Lung Cancer Undergoing Radical Resection

被引:98
作者
Bayarri-Lara, Clara [1 ]
Ortega, Francisco G. [2 ]
Ladron de Guevara, Antonio Cueto [1 ]
Puche, Jose L. [2 ,3 ]
Ruiz Zafra, Javier [1 ]
de Miguel-Perez, Diego [2 ]
Sanchez-Palencia Ramos, Abel [1 ]
Fernando Giraldo-Ospina, Carlos [1 ]
Navajas Gomez, Juan A. [1 ]
Delgado-Rodriguez, Miguel [4 ]
Lorente, Jose A. [2 ,5 ]
Jose Serrano, Maria [2 ,3 ]
机构
[1] Virgen de las Nieves Univ Hosp, Dept Thorac Surg, Ave Fuerzas Armadas 2, Granada 18014, Spain
[2] Univ Granada, GENYO, Ctr Genom & Oncol Res, Pfizer,Andalusian Reg Govt, PTS Granada Ave Ilustrac 114, Granada 18016, Spain
[3] San Cecilio Clin Univ Hosp, Integral Oncol Div, Ave Dr Oloriz 16, Granada 18012, Spain
[4] Univ Jaen, CIBERESP, Div Prevent Med & Publ Hlth, Campus Lagunillas, Jaen 23071, Spain
[5] Univ Granada, Dept Legal Med, Lab Genet Identificat, Avda Madrid 11, Granada 18012, Spain
关键词
PERIPHERAL-BLOOD; EGFR; EXPRESSION; SURVIVAL;
D O I
10.1371/journal.pone.0148659
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Background Surgery is the treatment of choice for patients with non-small cell lung cancer (NSCLC) stages I-IIIA. However, more than 20% of these patients develop recurrence and die due to their disease. The release of tumor cells into peripheral blood (CTCs) is one of the main causes of recurrence of cancer. The objectives of this study are to identify the prognostic value of the presence and characterization of CTCs in peripheral blood in patients undergoing radical resection for NSCLC. Patients and Methods 56 patients who underwent radical surgery for previously untreated NSCLC were enrolled in this prospective study. Peripheral blood samples for CTC analysis were obtained before and one month after surgery. In addition CTCs were phenotypically characterized by epidermal growth factor receptor (EGFR) expression. Results 51.8% of the patients evaluated were positive with the presence of CTCs at baseline. A decrease in the detection rate of CTCs was observed in these patients one month after surgery (32.1%) (p = 0.035). The mean number of CTCs was 3.16 per 10 ml (range 0-84) preoperatively and 0.66 (range 0-3) in postoperative determination. EGFR expression was found in 89.7% of the patients at baseline and in 38.9% patients one month after surgery. The presence of CTCs after surgery was significantly associated with early recurrence (p = 0.018) and a shorter disease free survival (DFS) (p =.008). In multivariate analysis CTC presence after surgery (HR = 5.750, 95% CI: 1.50-21.946, p = 0.010) and N status (HR = 0.296, 95% CI: 0.091-0.961, p = 0.043) were independent prognostic factors for DFS. Conclusion CTCs can be detected and characterized in patients undergoing radical resection for non-small cell lung cancer. Their presence might be used to identify patients with increased risk of early recurrence.
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共 21 条
[1]  
[Anonymous], CLIN CANCER RES IN P
[2]   Landscape of EGFR signaling network in human cancers: Biology and therapeutic response in relation to receptor subcellular locations [J].
Han, Woody ;
Lo, Hui-Wen .
CANCER LETTERS, 2012, 318 (02) :124-134
[3]   Detection of Circulating Tumor Cells from Lung Cancer Patients in the Era of Targeted Therapy: Promises, Drawbacks and Pitfalls [J].
Hofman, V. ;
Ilie, M. ;
Long, E. ;
Guibert, N. ;
Selva, E. ;
Washetine, K. ;
Mograbi, B. ;
Mouroux, J. ;
Venissac, N. ;
Reverso-Meinietti, J. ;
Milano, G. ;
Mazieres, J. ;
Marquette, C. -H. ;
Paterlini-Brechot, P. ;
Hofman, P. .
CURRENT MOLECULAR MEDICINE, 2014, 14 (04) :440-456
[4]   Preoperative Circulating Tumor Cell Detection Using the Isolation by Size of Epithelial Tumor Cell Method for Patients with Lung Cancer Is a New Prognostic Biomarker [J].
Hofman, Veronique ;
Bonnetaud, Christelle ;
Ilie, Marius I. ;
Vielh, Philippe ;
Vignaud, Jean Michel ;
Flejou, Jean Francois ;
Lantuejoul, Sylvie ;
Piaton, Eric ;
Mourad, Nadine ;
Butori, Catherine ;
Selva, Eric ;
Poudenx, Michel ;
Sibon, Stephanie ;
Kelhef, Sabrina ;
Venissac, Nicolas ;
Jais, Jean-Philippe ;
Mouroux, Jerome ;
Molina, Thierry Jo ;
Hofman, Paul .
CLINICAL CANCER RESEARCH, 2011, 17 (04) :827-835
[5]   Clinical Significance of Circulating Tumor Cells, Including Cancer Stem-Like Cells, in Peripheral Blood for Recurrence and Prognosis in Patients With Dukes' Stage B and C Colorectal Cancer [J].
Iinuma, Hisae ;
Watanabe, Toshiaki ;
Mimori, Koshi ;
Adachi, Miki ;
Hayashi, Naoko ;
Tamura, Junko ;
Matsuda, Keiji ;
Fukushima, Ryoji ;
Okinaga, Kota ;
Sasako, Mitsuru ;
Mori, Masaki .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (12) :1547-1555
[6]   Detection of circulating tumor cells in the context of treatment Prognostic value in breast cancer [J].
Jose Serrano, Maria ;
Sanchez-Rovira, P. ;
Delgado-Rodriguez, M. ;
Gaforio, J. J. .
CANCER BIOLOGY & THERAPY, 2009, 8 (08) :671-675
[7]   Local Recurrence After Surgery for Early Stage Lung Cancer An 11-Year Experience With 975 Patients [J].
Kelsey, Chris R. ;
Marks, Lawrence B. ;
Hollis, Donna ;
Hubbs, Jessica L. ;
Ready, Neal E. ;
D'Amico, Thomas A. ;
Boyd, Jessamy A. .
CANCER, 2009, 115 (22) :5218-5227
[8]   Evaluation and Prognostic Significance of Circulating Tumor Cells in Patients With Non-Small-Cell Lung Cancer [J].
Krebs, Matthew G. ;
Sloane, Robert ;
Priest, Lynsey ;
Lancashire, Lee ;
Hou, Jian-Mei ;
Greystoke, Alastair ;
Ward, Tim H. ;
Ferraldeschi, Roberta ;
Hughes, Andrew ;
Clack, Glen ;
Ranson, Malcolm ;
Dive, Caroline ;
Blackhall, Fiona H. .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (12) :1556-1563
[9]   Detection of mutations in EGFR in circulating lung-cancer cells [J].
Maheswaran, Shyamala ;
Sequist, Lecia V. ;
Nagrath, Sunitha ;
Ulkus, Lindsey ;
Brannigan, Brian ;
Collura, Chey V. ;
Inserra, Elizabeth ;
Diederichs, Sven ;
Iafrate, A. John ;
Bell, Daphne W. ;
Digumarthy, Subba ;
Muzikansky, Alona ;
Irimia, Daniel ;
Settleman, Jeffrey ;
Tompkins, Ronald G. ;
Lynch, Thomas J. ;
Toner, Mehmet ;
Haber, Daniel A. .
NEW ENGLAND JOURNAL OF MEDICINE, 2008, 359 (04) :366-377
[10]   SIMULATION STUDY OF CONFOUNDER-SELECTION STRATEGIES [J].
MALDONADO, G ;
GREENLAND, S .
AMERICAN JOURNAL OF EPIDEMIOLOGY, 1993, 138 (11) :923-936