AC099850.3/NCAPG Axis Predicts Poor Prognosis and is Associated with Resistance to EGFR Tyrosine-Kinase Inhibitors in Lung Adenocarcinoma

BACKGROUND: TKI-acquired resistance markedly interferes with treatment of lung cancer patients with EGFR mutant features. Long non-coding RNAs (lncRNAs) modify EGFR-TKI resistance during tumor progression. Non-structural maintenance of chromosomes condensin I complex subunit G (NCAPG) is a mitosis-related protein that is involved in tumorigenesis. We investigated the potential regulatory lncRNAs of NCAPG in lung adenocarcinoma (LUAD) and assessed their roles in EGFR-TKI resistance. METHODS: Data for 1678 lung cancer patients were retrieved from TCGA and GEO databases and used to evaluate NCAPG and lncRNAs expressions, as well as their prognostic significance in LUAD. Protein levels of NCAPG in LUAD were validated by immuno-histochemistry. To assess the relationship between NCAPG levels and EGFR-TKIs sensitivity, a cohort of 57 LUAD patients administered with EGFR-TKIs was used. RESULTS: Both NCAPG and lncRNA AC099850.3 were over-expressed in LUAD tissues, and correlated with tumor progression and poor prognosis in LUAD. LncRNA AC099850.3 was identified as a potential regulator of NCAPG expressions. The AC099850.3/NCAGP axis was markedly correlated with EGFR mutations and IC(50) of EGFR-TKIs. Besides, elevated NCAPG levels were associated with EGFR-TKIs resistance in 57 LUAD patients undergoing TKIs treatment. Gene set enrichment analysis revealed that both AC099850.3 and NCAGP were abundant in the cell cycle and the p53 signaling pathway. CONCLUSION: The AC099850.3/NCAPG axis is a potential prognostic predictor and therapeutic biomarker for EGFR-TKIs in LUAD.