Long non-coding RNAs (lncRNAs) are RNAs longer than 200 nucleotides that do not code for protein. Recently, the lncRNA-X was implicated in physiological and pathological processes such as proliferation, invasion, and metastasis. However, the roles of lncRNA-X in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma are poorly understood.
qRT-PCR was used to measure lncRNA-X expression in 5 lung cancer cell lines (A549, H1299, PC9, H4006, H1975). Non–small cell lung cancer (NSCLC) cells with knockout of lncRNA-X were generated with a CRISPR-Cas9 system and used to investigate the effect of lncRNA-X on gefitinib-induced cell death in an MTT assay. We studied 21 patients with recurrent postoperative EGFR-mutant lung adenocarcinoma (exon 19 deletion in 11, L858R in 8, G719C in 2) treated with gefitinib during the period from January 2008 to January 2018. Relative quantification of lncRNA-X expression on real-time PCR analysis of formalin-fixed paraffin-embedded slides of surgical specimens was used to determine lncRNA-X expressions in tumors and adjacent normal tissues.
lncRNA-X expression was greater in the cell lines harboring EGFR exon 19 deletions and L858R (PC-9, H4006, H1975) than in those without EGFR mutation (A549, H1299) (p < 0.001). H1299 cells with lncRNA-X knockout were more sensitive to gefitinib. lncRNA-X expressions were significantly greater in NSCLC tumors than in adjacent normal tissues (p < 0.01). Patients with high lncRNA-X expression in tumors had significantly shorter progression-free survival (PFS) after gefitinib therapy and overall survival than did those with low expression (median PFS: 304 vs 1125 days, p = 0.046; MST: 1271 vs 1876 days, p = 0.014).
lncRNA-X expression in EGFR-mutant adenocarcinoma is associated with shorter overall survival and shorter PFS after gefitinib therapy.
Clinical trial identification
Legal entity responsible for the study
Toho University School of Medicine.
Has not received any funding.
All authors have declared no conflicts of interest.