Prognosis of non-small cell lung cancer patients by detecting circulating cancer cells in the peripheral blood with multiple marker genes.
OBJECTIVE
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.


METHODS
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 Lc 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 Lc 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.


CONCLUSIONS
Circulating cancer cell detection by a panel of markers and the Lc 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.
Sher
Yuh-Pyng
YP
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Shih
Jin-Yuan
JY
Yang
Pan-Chyr
PC
Roffler
Steve R
SR
Chu
Yi-Wen
YW
Wu
Cheng-Wen
CW
Yu
Chia-Li
CL
Peck
Konan
K
D000368:Aged; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D017931:DNA Primers / Q000737:chemistry; D019992:Databases as Topic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism; D009360:Neoplastic Cells, Circulating / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D017931:DNA Primers; D012313:RNA