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Prognosis of Non–Small Cell Lung Cancer Patients by Detecting Circulating Cancer Cells in the Peripheral Blood with Multiple Marker Genes

¹ Institute of Biomedical Sciences, Academia Sinica; ² Department of Internal Medicine, National Taiwan University Hospital and ³ Institute of Molecular Medicine, National Taiwan University; and ⁴ National Health Research Institutes, Taipei, Taiwan, Republic of China

Requests for reprints: Konan Peck, Institute of Biomedical Sciences, Academia Sinica, 128, Section 2, Academia Road, Taipei, Taiwan 115, Republic of China. Phone: 886-2-2652-3072; Fax: 886-2-2785-8594; E-mail: konan{at}ibms.sinica.edu.tw.

Purpose: Current lung cancer staging and prognosis methods are based on imaging methods, which may not be sensitive enough for early and accurate detection of metastasis. This study aims to validate the use of a panel of markers for circulating cancer cell detection to improve the accuracy of cancer staging, prognosis, and as a rapid assessment of therapeutic response.

Experimental Design: We analyzed the National Cancer Institute-Cancer Genome Anatomy Project database to identify potential marker genes for the detection of circulating cancer cells in peripheral blood. Nested real-time quantitative PCR and a scoring method using cancer cell load L_c were employed to correlate the amount of circulating cancer cells with clinical outcomes in 54 non–small cell lung cancer (NSCLC) patients. The Kaplan-Meier method was employed for analysis of prognostic variables.

Results: A panel of four marker genes was identified and experimentally validated. With these marker genes, we achieved an overall positive detection rate of 72% for circulating cancer cells in the peripheral blood of NSCLC patients. Patients who had higher L_c values had worse outcomes and shorter survival times. Patients with poor therapeutic response were revealed by positive detection of circulating cancer cells after therapy. The results correlated well with the patients' survival time.

Conclusion: Circulating cancer cell detection by a panel of markers and the L_c scoring method can supplement the current tumor, node, metastasis staging method for improved prognosis and for rapid assessment of therapeutic response. Together, they may facilitate the design of better therapeutic strategies for the treatment of NSCLC patients.

Key Words: lung cancer prognosis • marker genes • cancer staging • circulating cancer cell detection • metastasis

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