Purpose: Currently focuses on the identification of early-stage lung cancer (ESLC) is the core of the prevention and treatment of lung cancer, which is desperately needed throughout the world to improve lung cancer survival. Our study has primarily aimed at exosome-derived miRNAs in the detection of ESLC and discrimination between Benign lung nodules(BLN) and Healthy individuals. We aim to determine sensitive and specific liquid biopsy-based biomarkers in tackling ESLC.

Methods: Discovering the non-invasive serum exosomal based miRNAs (sEXO-miRNAs) biomarkers through next-generation sequencing (NGS)in 9 participants (ESLC-3, BLN-3 and Healthy-3) and validated by 143 (ESLC-46, BLN-46 and Healthy-51) recruiters via RT-PCR in a cohort of Zhongda Hospital affiliated to the medical school of Southeast University, Nanjing, China.

Results: By doing NGS, we have discovered 769 differently expressed miRNAs mutual between the three groups. Amid those miRNAs, we have selected the topmost highly up-or down-regulated significant sEXO-miRNAs as biomarkers following certain threshold and statistical criteria, which were sEXO-miR-424-5p, sEXO-miR-512-5p, and sEXo-miR-1271-5p for subsequent validation in 3 groups of a single-center cohort. The area under the receiver operating curve (AUC-ROC) of 3 individual miRNAs in between three groups ranged from 0.633 to 0.995 (95%CI: 0.515~1.000 ranged, p<0.0274~p<0.0001) in the validation cohort. Overall in the ESLC vs BLN group, the combination of the three sEXO-miRNAs'AUC was 0.824 (95%CI: 0.738~0.909, p<0.0001) whereas sensitivity, specificity, PPV, NPV and accuracy were 77.08%, 79.55%, 80.43%, 76.09% and 78.26% respectively by logistic regression analysis.

Conclusion: Our study discovered significant three differentials expressed sEXO-miRNAs (hsa-miR-424-5p, hsa-miR-512-5p, and hsa-miR-1271-5p), and validated throughout in between ESLC, BLN and healthy individuals. These sEXO-miRNAs provided substantial diagnostic efficacy towards predicting ESLC and accurately discriminate with BLN and healthy recruiters. Therefore, our novel sEXO-miRNAs as biomarkers for prior detection ESLC is quite promising in clinical practice and can be used for precision-based diagnosing purposes.

Citation Format: Nishant Patel, Haijun Zhang, Lili Ren. Serum Based Exosomal miRNAs as in Novel Biomarkers for the Initial Prediction of Early-Stage Lung Cancer [abstract]. In: Proceedings of the 9th Annual Symposium on Global Cancer Research; Global Cancer Research and Control: Looking Back and Charting a Path Forward; 2021 Mar 10-11. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2021;30(7 Suppl):Abstract nr 58.