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Development of transcriptomic biomarker signature in human saliva to detect lung cancer

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Abstract

Lung cancer is the leading cause of cancer death for both men and women worldwide. Since most of the symptoms found for lung cancer are nonspecific, diagnosis is mostly done at late and progressed stage with the consecutive poor therapy outcome. Effective early detection techniques are sorely needed. The emerging field of salivary diagnostics could provide scientifically credible, easy-to-use, non-invasive and cost-effective detection methods. Recent advances have allowed us to develop discriminatory salivary biomarkers for a variety of diseases from oral to systematic diseases. In this study, salivary transcriptomes of lung cancer patients were profiled and led to the discovery and pre-validation of seven highly discriminatory transcriptomic salivary biomarkers (BRAF, CCNI, EGRF, FGF19, FRS2, GREB1, and LZTS1). The logistic regression model combining five of the mRNA biomarkers (CCNI, EGFR, FGF19, FRS2, and GREB1) could differentiate lung cancer patients from normal control subjects, yielding AUC value of 0.925 with 93.75 % sensitivity and 82.81 % specificity in the pre-validation sample set. These salivary mRNA biomarkers possess the discriminatory power for the detection of lung cancer. This report provides the proof of concept of salivary biomarkers for the non-invasive detection of the systematic disease. These results poised the salivary biomarkers for the initiation of a multi-center validation in a definitive clinical context.

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Abbreviations

CT:

Computerized tomography

MACs:

Malignancy-associated changes

ROC:

Receiver-operating characteristic

AUC:

Calculation of the area under the curve

qPCR:

Quantitative polymerase chain reaction

COPD:

Chronic obstructive pulmonary disease

EGFR:

Epidermal growth factor receptor

BRAF:

v-raf murine sarcoma viral oncogene homolog B1

LZTS1:

Leucine zipper, putative tumor suppressor 1

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Acknowledgments

Supported by the University of California Tobacco Research Related Research Program (TRDRP, 20PT-0032) and DOD Lung Cancer Research Program (LC110207). DTWW is also supported by the Felix & Mildred Yip Endowed Professorship.

Conflict of interest

HX, LZ, HZ, and DTWW have patent application (US 2011/0207622 A1) pertaining to this work. DTWW is the co-founder of RNAmeTRIX. The other authors disclosed no potential conflicts of interests.

Author information

Author notes

  1. Hui Zhou

    Present address: Genome Sciences Resource, Vanderbilt University Medical Center, Nashville, TN, USA

Authors and Affiliations

  1. School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA, 90095, USA

    Lei Zhang, Hua Xiao, Hui Zhou, Jieping Yang, Ole Brinkmann, Xinmin Yan, David Akin, No-Hee Park & David T. W. Wong

  2. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    David Chia

  3. Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Jay M. Lee, David Chia, No-Hee Park & David T. W. Wong

  4. Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    David Elashoff

  5. Division of Head and Neck Surgery/Otolaryngology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    David T. W. Wong

  6. Henry Samueli School of Engineering and Applied Science, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    David T. W. Wong

  7. Dental Research Institute, School of Dentistry, University of California-Los Angeles, 10833 Le Conte Avenue, 73-017 CHS, Los Angeles, CA, 90095, USA

    David T. W. Wong

  8. David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Silverio Santiago & No-Hee Park

  9. Department of Surgery, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Jay M. Lee

  10. Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, 90095, USA

    Edward B. Garon

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  1. Lei Zhang
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  2. Hua Xiao
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  3. Hui Zhou
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Corresponding author

Correspondence to Hua Xiao.

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L. Zhang and H. Xiao contributed equally to this work.

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Zhang, L., Xiao, H., Zhou, H. et al. Development of transcriptomic biomarker signature in human saliva to detect lung cancer. Cell. Mol. Life Sci. 69, 3341–3350 (2012). https://doi.org/10.1007/s00018-012-1027-0

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