Prognostic Value of miR-10a-3p in Non-Small Cell Lung Cancer Patients.

Abstract

Purpose: Poor lung cancer patients' outcomes and survival rates demand the discovery of new biomarkers for the specific, significant, and less invasive detection of non-small cell lung cancer (NSCLC) progression. The present study aimed to investigate the potential of miRNA expression as biomarkers in NSCLC utilizing a preclinical cell culture setup based on screening of miRNAs in NSCLC cells grown in 3D cell culture.

Patients and methods: The study was performed using lung cancer cell lines, varying in different levels of aggressiveness: NCI-H1299, A549, Calu-1, and NCI-H23, as well as noncancerous bronchial epithelial cell line HBEC3, which were grown in 3D cell culture. Total RNA from all cell lines was extracted and small RNA libraries were prepared and sequenced using the Illumina NGS platform. The expression of 8 differentially expressed miRNAs was further validated in 89 paired tissue specimens and plasma samples obtained from NSCLC patients. Statistical analysis was performed to determine whether miRNA expression and clinicopathological characteristics of NSCLC patients could be considered as independent factors significantly influencing PFS or OS.

Results: Differentially expressed miRNAs, including let-7d-3p, miR-10a-3p, miR-28-3p, miR-28-5p, miR-100-3p, miR-182-5p, miR-190a-5p, and miR-340-5p, were identified through next-generation sequencing in NSCLC cell lines with varying levels of aggressiveness. Validation of patient samples, including tumor and plasma specimens, revealed that out of the 8 investigated miRNAs, only plasma miR-10a-3p showed a significant increase, which was associated with significantly extended progression-free survival (PFS) (p=0.009). Furthermore, miR-10a-3p in plasma emerged as a statistically significant prognostic variable for NSCLC patients' PFS (HR: 0.5, 95% CI: 0.3-0.9, p=0.029).

Conclusion: Our findings of screening miRNA expression patterns in NSCLC cells grown in 3D cell culture indicated that the expression level of circulating miR-10a-3p has the potential as a novel non-invasive biomarker to reflect the short-term prognosis of NSCLC patients.