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Clinical Investigations: CANCER |

Overexpression of Circulating c-Met Messenger RNA Is Significantly Correlated With Nodal Stage and Early Recurrence in Non-Small Cell Lung Cancer*

Tian-Lu Cheng, PhD; Mei-Yin Chang, BS; Sung-Yu Huang, BS; Chau-Chyun Sheu, MD; Eing-Long Kao, MD, FCCP; Yu-Jen Cheng, MD; Inn-Wen Chong, MD, FCCP
Author and Funding Information

*From the MedicoGenomic Research Center (Ms. Chang), School of Biomedical Science and Environmental Biology (Dr. T-L Cheng), Department of Surgery (Drs. Kao and Y-J Cheng), and Department of Internal Medicine (Dr. Sheu), Kaohsiung Medical University, Kaohsiung; Sung-Hua Gene Co., Ltd. (Mr. Huang), Kaohsiung, Taiwan; and the Department of Internal Medicine (Dr. Chong), Kaohsiung Municipal Hsaio-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.

Correspondence to: Inn-Wen Chong, MD, FCCP, Department of Internal Medicine, Kaohsiung Medical University, 100 Shih-Chuan First Rd, Kaohsiung, 807 Taiwan; e-mail: chong@cc.kmu.edu.tw



Chest. 2005;128(3):1453-1460. doi:10.1378/chest.128.3.1453
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Background: The c-met receptor and its ligand hepatocyte growth factor have been shown to be involved in tumor invasiveness and metastasis. Overexpression of c-met has been demonstrated in lung cancer tissues and cell lines, but the expression of c-met in peripheral blood (circulating c-met) has not been addressed. The molecular monitoring of circulating c-met could be helpful for selecting patients for adjuvant therapy.

Objectives: To investigate the expression of circulating c-met in non-small cell lung cancer (NSCLC) patients and to assess its prognostic implications.

Methods: We quantified the levels of c-met messenger RNA (mRNA) in paired tumor and normal lung tissues and their peripheral bloods in 45 patients with NSCLC by real-time polymerase chain reaction (PCR). The expression status of c-met protein in tumor tissues was further evaluated by immunohistochemistry.

Results: c-Met mRNA was significantly higher by 1.5 to 11 times in 34 of 45 tumor tissues (75.5%) than it was in their normal counterparts by real-time PCR. A comparison of this assay to immunohistochemistry suggested that real-time PCR was more sensitive than immunohistochemistry (27 of 45 tumor tissues, 60.0%) for the detection of c-met (p = 0.016). Of these patients with overexpression of c-met in tumors, 67.6% (23 of 34 patients) expressed higher amounts of circulating c-met by 1.4 to 8 times that of the normal control subjects. In addition, overexpression of circulating c-met was significantly correlated with nodal (N) stage (p = 0.011), but weakly correlated with tumor (T) stage (p = 0.056) and overall stages (p = 0.054) in patients with NSCLC. However, no correlations were found among circulating c-met and other factors such as age, gender, and pathologic types. Moreover, by univariate analysis, circulating c-met overexpression and pathologic stages (including T and N stages) were the most important factors correlated with early recurrence (p < 0.05). Only the circulating c-met remained as an independent predictor of early recurrence (hazard ratio, 3.94; 95% confidence interval, 1.17 to 13.33; p = 0.027) after Cox regression multivariate analysis.

Conclusions: Overexpression of circulating c-met is significantly correlated with the N stage and early recurrence. Moreover, early recurrence is frequently noted in patients with overexpression of circulating c-met, indicating that circulating c-met is an independent negative prognostic indicator in NSCLC.

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