Development of transcriptomic biomarker signature in human saliva to detect lung cancer.
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.
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Lei
L
Zhang
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Hua
H
Xiao
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Hui
H
Zhou
David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Silverio
S
Santiago
Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Jay M
JM
Lee
Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Edward B
EB
Garon
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Jieping
J
Yang
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Ole
O
Brinkmann
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
Xinmin
X
Yan
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
David
D
Akin
Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
David
D
Chia
Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA.
David
D
Elashoff
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
No-Hee
NH
Park
School of Dentistry and Dental Research Institute, University of California, 10833 Le Conte Avenue, 73-024 CHS, Los Angeles, CA 90095, USA.
David T W
DTW
Wong
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D055515:Cysteine-Rich Protein 61 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005346:Fibroblast Growth Factors / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012044:Regression Analysis; D012463:Saliva / Q000502:physiology*; D012907:Smoking; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D004268:DNA-Binding Proteins; C117476:FGF19 protein, human; C106534:FRS2 protein, human; C416830:GREB1 protein, human; C118711:LZTS1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D025521:Tumor Suppressor Proteins; D005346:Fibroblast Growth Factors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf