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Int J Clin Exp Pathol 2011;4(6):575-586

Original Article
Plasma microRNAs as novel biomarkers for early detection of lung cancer

Dali Zheng, Shadi Haddadin, Yong Wang, Li-Qun Gu, Michael C. Perry, Carl E. Freter, and Michael X. Wang

Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri School of Medicine, 115 Business Loop
70 West, Columbia, MO 65203, USA; Department of Biochemistry and Molecular Biology, Fujian Medical University, 88 Jiaotong Rd, Fuzhou,
350004, P. R. China; Division of Hematology/Medical Oncology, Department of Internal Medicine, Ellis Fischel Cancer Center, University of
Missouri, 115 Business Loop 70 West, Columbia, MO 65203, USA; Department of Biological Engineering and Dalton Cardiovascular Research
Center, University of Missouri, Columbia, MO 65211, USA.

Received August 22, 2011; accepted August 5, 2011; Epub August 8, 2011; published August 15, 2011

Abstract: A diagnosis of lung cancer at its early stages is vital for improving the survival rate of patients. MicroRNAs (miRNAs), a family of 19- to
25-nucleotide non-coding small RNAs, are frequently dysregulated in lung cancer. The objective of this study was to investigate the potential of
circulating miRNAs for early detection of lung cancer. We searched the published literature for the miRNA microarray data of primary lung
cancer and selected 15 miRNAs that were most frequently up-regulated in lung cancer tissues. Total plasma RNA including miRNAs was
isolated, polyadenylated and reverse-transcribed into cDNAs. The levels of miRNAs were determined by real-time RT-PCR in 74 lung cancer
patients and 68 age-matched cancer-free controls. We found that the levels of miR-155, miR-197, and miR-182 in the plasma of lung cancer
including stage I patients were significantly elevated compared with controls (P<0.001). The combination of these 3 miRNAs yielded 81.33%
sensitivity and 86.76% specificity in discriminating lung cancer from controls. The levels of miR-155 and miR-197 were higher in the plasma
from lung cancer patients with metastasis than in those without metastasis (P<0.05) and were significantly decreased in responsive patients
during chemotherapy (P<0.001). These results indicate that miR-155, miR-197, and miR-182 can be potential non-invasive biomarkers for
early detection of lung cancer. (IJCEP1108001).

Keywords: Plasma microRNA, lung cancer, real-time RT-PCR, early diagnosis, metastasis, prognosis

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Address all correspondence to:
Michael X. Wang, MD, PhD
Department of Pathology and Anatomical Sciences
Ellis Fischel Cancer Center
University of Missouri School of Medicine
115 Business Loop 70 West
Columbia, MO 65203, USA.
Tel: (573)-882-1276, Fax: (573)-884-5206
E-mail:
wangmx@health.missouri.edu