Non-small cell 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 US. However, the poor specificity of LDCT has raised significant concerns about its high chance of false positive results. This study aimed to develop a blood miRNA based molecular diagnostic test for the detection of early stage lung cancer.
The three-phase study was designed with a total of 948 cancer-free controls, and 768 patients with NSCLC. 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 form the LDCT screening program in Zhejiang province, China. Differentially expressed miRNAs were further validated in another Chinese case-control cohort (n = 432) collected from similar sources and a white case-control cohort (n = 218) collected from the EU and US. Finally, the identified miRNAs were further assessed in three additional Asian cohorts: a Chinese cohort collected from the similar sources (n = 237), a Chinese cohort collected from independent sources (n = 340), and a Singaporean cohort (Chinese, Malay and Indian population) (n = 65).
29 miRNA biomarkers with p-value (FDR) <0.01 and more than one z-score (standardized score) difference were identified in the discovery phase. 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 0.936 (95% CI, 0.912-0.957) AUC for the Chinese validation cohort and 0.970 (95% CI, 0.939-0.986) AUC for the white validation cohort. The 5-miRNA biomarker panel were then further validated in three additional Asian cohorts, giving 0.973 (95% CI 0.950-0.986) AUC for similarly sourced Chinese cohort, 0.916 (95% CI, 0.852-0.949) AUC for the independently sourced Chinese cohort, and 0.911 (95% CI, 0.822-0.963) AUC for the Singaporean cohort, respectively.
The five-miRNA panel in serum may serve as a potential non-invasive biomarker in detecting early stage NSCLC.
Clinical trial identification
Legal entity responsible for the study
Zhejiang Cancer Hospital & Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology of Zhejiang Province.
Has not received any funding.
All authors have declared no conflicts of interest.