1. Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive Detection of Gastric Cancer
- Author
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Jae-Moon Bae, Min-Sun Lee, Xiaoyan Wang, Janice M. Yoshizawa, Su Mi Kim, Julie Kanjanapangka, T.S. Sohn, David E. Elashoff, Jun Haeng Lee, David T.W. Wong, Rayun Choi, Yong Kim, Shigeo Ishikawa, Kyoung-Mee Kim, So Young Kang, David Akin, Jae J. Kim, Xinmin Yan, David Chia, Jun Ho Lee, Byung-Hoon Min, Min-Gew Choi, Sung Kim, Tristan Grogan, Wei Liao, and Feng Li
- Subjects
0301 basic medicine ,Oncology ,Saliva ,Messenger ,Medical Biotechnology ,Clinical Biochemistry ,Medical Biochemistry and Metabolomics ,Cohort Studies ,0302 clinical medicine ,Prospective Studies ,Prospective cohort study ,General Clinical Medicine ,Cancer ,screening and diagnosis ,Tumor ,Gene Expression Regulation, Neoplastic ,Detection ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Biotechnology ,4.2 Evaluation of markers and technologies ,medicine.medical_specialty ,Clinical Sciences ,Sensitivity and Specificity ,Article ,03 medical and health sciences ,Clinical Research ,Stomach Neoplasms ,Internal medicine ,microRNA ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,RNA, Messenger ,Dental/Oral and Craniofacial Disease ,Neoplastic ,business.industry ,Prevention ,Gene Expression Profiling ,Biochemistry (medical) ,Case-control study ,Reproducibility of Results ,medicine.disease ,Microarray Analysis ,4.1 Discovery and preclinical testing of markers and technologies ,Gene expression profiling ,MicroRNAs ,030104 developmental biology ,Gene Expression Regulation ,ROC Curve ,Case-Control Studies ,RNA ,Digestive Diseases ,business ,Transcriptome ,Biomarkers ,Extracellular RNA - Abstract
BACKGROUND Biomarkers are needed for noninvasive early detection of gastric cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as potential clinical evaluation tools for GC. METHODS Unstimulated whole saliva samples were prospectively collected from 294 individuals (163 GC and 131 non-GC patients) who underwent endoscopic evaluation at the Samsung Medical Center in Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and mRNA biomarker candidates were verified with reverse transcription quantitative real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva samples from GC and non-GC patients. Validated individual markers were configured into a best performance panel. RESULTS We identified 30 mRNA and 15 miRNA candidates whose expression pattern associated with the presence of GC. Among them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by RT-qPCR and further validated with the independent cohort (n = 200). The configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2 miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72–0.89). When combined with demographic factors, the AUC of the biomarker panel reached 0.87 (95% CI, 0.80–0.93). CONCLUSIONS We have discovered and validated a panel of salivary exRNA biomarkers with credible clinical performance for the detection of GC. Our study demonstrates the potential utility of salivary exRNA biomarkers in screening and risk assessment for GC.
- Published
- 2018