Lung cancer is the most prevalent cancer and leading cause of cancer death worldwide. Low-dose spiral computed tomography (LDCT) scan is being recommended as a screening test for smokers in the U.S. However, the poor specificity (73% specificity at 94% sensitivity) of LDCT has raised significant concern for its high chance of false positive (96% of LDCT positives are benign nodules). This study aims to develop a blood (serum) miRNA based molecular diagnostic test for the detection of early stage lung cancer. In the discovery phase, more than 400 miRNAs were profiled with MiRXES's qPCR based high throughput assay platform through a highly defined Chinese male smoker case-control cohort (n=424) where the cases were collected from Zhejiang Cancer Hospital and the controls were collected from the LDCT screening program in Zhejiang province, China. 29 miRNA biomarkers with p-value (FDR) < 0.01 and more than one z-score (standardized score) difference were identified and validated in another Chinese case-control cohort (n=432) collected from similar sources and a Caucasian case-control cohort (n=218) collected from EU and US. 18 out of the 29 miRNA biomarkers were validated in both cohorts (p-value < 0.01 and z-score >0.4). With multiple time of two-fold cross-validation, 5 miRNAs were found to be minimally required to form the biomarker panel for the accurate prediction of early stage lung cancer and the panel gives 0.984 (95% CI 0.973-0.991) AUC for the discovery cohort, 0.936 (95% CI 0.912-0.957) AUC for the Chinese validation cohort and 0.970 (95% CI 0.939-0.986) AUC for the Caucasian validation cohort. The 5-miRNA biomarker panel were then further validated in three additional Asian cohorts: a Chinese cohort collected from the similar sources (0.973, 95% CI 0.950-0.986, AUC), a Chinese cohort collected from independent sources (0.916, 95% CI 0.852-0.949, AUC) and a Singaporean cohort (Chinese, Malay and Indian population) (0.911, 95% CI 0.822-0.963, AUC).

Citation Format: Lisha Ying, Ruiyang Zou, Lingbin Du, Lei Shi, Nan Zhang, Jiaoyue Jin, Junzhou Wu, Fanrong Zhang, Kaiyan Chen, Herbert Yu, Weimin Mao, Dan Su. Development and validation of a serum miRNA biomarker panel for the detection of early stage lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4408.