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The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer

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Abstract

Background

A high level of circulating DNA (cirDNA) in cancer patients has been correlated with poor outcomes. Studies have demonstrated the critical contributions of the tumor-derived cirDNA. In this report, we investigated the roles of the non-tumor-derived cirDNA (nt-cirDNA) in determining the prognosis of non-small cell lung cancer (NSCLC).

Materials and methods

Plasma samples from 58 advanced NSCLC patients and 52 controls were collected. The nt-cirDNA levels were assessed with qPCR assay to detect the unmethylation status of an epithelial-specific marker, the SHP-1 promoter 2 (unmethylated SHP1P2). Clinicopathological correlations were analyzed.

Results

There was a significant increase in the total amount of cirDNA in NSCLC patients compared with controls: 4.3 ng ml−1 [0.82–49.8] and 2.0 ng ml−1 [0.03–26.9], respectively (p < 0.01). An increased amount of the unmethylated SHP1P2 in advanced NSCLC was also detected: 3.4 ng ml−1 [1.2–24.8] versus 2.0 ng ml−1 [0.03–26.9] in the controls (p = 0.026). Survival analyses revealed that high levels of total cirDNA and unmethylated SHP1P2 were significantly associated with decreased survival. However, the total cirDNA had a better prognostic correlation than the unmethylated SHP1P2. Multivariate analysis identified total cirDNA (p = 0.004) and systemic treatment (p = 0.002) as independent prognostic parameters.

Conclusion

The level of total cirDNA in NSCLC is an important prognostic parameter that demonstrates the contributions from both tumor-derived sources and non-tumor-derived sources.

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Acknowledgments

This project was financially supported by The Royal Golden Jubilee., The Higher Education Research Promotion, The National Research University Project of Thailand, The Office of Higher Education Commission, The Ratchadaphiseksomphot Endowment Fund [HR1162A93)] and the National Science and Technology Development Agency (NSTDA), Thailand. The authors thank the nursing staff of the medical oncology unit for completing the blood sample collection from non-small lung cancer patients and Ms. Pornrutsami Jintaridth, at the Department of Tropical Nutrition and Food Science, Faculty of Tropical Medicine, Mahidol University, for providing valuable blood samples from healthy volunteers.

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We declare that we have no conflict of interest.

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Correspondence to Virote Sriuranpong.

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Vinayanuwattikun, C., Winayanuwattikun, P., Chantranuwat, P. et al. The impact of non-tumor-derived circulating nucleic acids implicates the prognosis of non-small cell lung cancer. J Cancer Res Clin Oncol 139, 67–76 (2013). https://doi.org/10.1007/s00432-012-1300-5

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  • DOI: https://doi.org/10.1007/s00432-012-1300-5

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