Profiling of cell-free miRNA in blood plasma yields a panel of lung cancer biomarkers - 11th International Symposium on Circulating Nucleic Acids in Plasma and Serum (CNAPS)

Ivan Zaporozhchenko ^1,2 Anastasia A. Ponomaryova ³ Elena Yu. Rykova ^1,2 Nadezhda V. Cherdyntseva ³ Oksana A. Pashkovskaya ⁴ Aleksandr A. Zheravin ⁴ Pavel P. Laktionov ^1,2

¹Laboratory of Molecular Medicine, Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia
²Laboratory of Biomedical Technologies, Meshalkin National Medical Research Center, Ministry of Health of the Russian Federation, Novosibirsk, Russia
³Laboratory of Molecular Oncology and Immunology, Tomsk National Research Medical Center, Tomsk, Russia
⁴Department of Oncology and Radiotherapy, Department of Oncology and Radiotherapy, Novosibirsk, Russia

Lung cancer (LC) is a major malignancy causing more than 1.3 million deaths worldwide annually. Early detection is critical for LC patients’ survival, but is rarely achieved and many patients are diagnosed at an advanced stage. Liquid biopsy offers an alternative to traditional diagnostic techniques. One of prospective biomarkers is plasma cell-free circulating miRNA, which has been linked to clinical manifestation, and genotype of lung tumours.

Here we describe the discovery and validation of miRNA biomarkers for LC in blood plasma. Study subjects included squamous cell carcinoma (SCC) and adenocarcinoma (AD) patients, individuals diagnosed with hyper- or metaplastic endobronchitis (EB) and cancer-free volunteers (HD). Plasma miRNA were isolated using previously developed original phenol-free protocol and profiled using miRCURY LNA qPCR platform. In the discovery phase profiles of circulating miRNAs in blood plasma of 20 LC patients (14 SCC, 6 AD) and 10 healthy individuals (HD) were investigated. After ratio-based normalization was applied, 241 ratios (98 individual miRNAs) with significantly different expression between LC patients and HD (p<0.05, Benjamini-Hochberg corrected) were identified. Using LASSO penalized regression and filtering of haemolysis-associated miRNAs, a set of 19 miRNAs was selected and their expression was validated in an independent sample (30 LC patients, 20 HD and 10 EB patients). Expression of 20 miRNA ratios was significantly different between LC and both control groups. Using these data, we developed bootstrap-enhanced LASSO-penalized logistic regression model comprised of 10 miRNA ratios (14 miRNAs) that discriminated between LC patients and non-cancer groups with 97.9% accuracy.

Thus, significant association of plasma miRNA expression with lung cancer was discovered, and a prospective miRNA biomarker panel has been developed for further independent validation.

Elena Yu. Rykova and Pavel P. Laktionov acknowledge financial support within the framework of the Russian state funded budget project # АААА-А17-117020210026-2 to the ICBFM SB RAS.