184P - Long non-coding RNA UCA1 induces acquired resistance of EGFR-TKIs in non-small cell lung cancer

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Translational Research
Non-Small Cell Lung Cancer
Basic Principles in the Management and Treatment (of cancer)
Presenter Ningning Cheng
Citation Annals of Oncology (2014) 25 (suppl_4): iv58-iv84. 10.1093/annonc/mdu326
Authors N. Cheng1, X. Li2, S. Ren3, W. Cai4, C. Zhou2
  • 1Department Of Medical Oncology, Shanghai Pulmonary Hospital,Tongji University Medical School Cancer Insititute, 200433 - Shanghai/CN
  • 2Lung Cancer Institute, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN
  • 3Oncology Department, Shanghai Pulmonary Hospital, Shanghai/CN
  • 4Medical Oncology, Shanghai Pulmonary Hospital, 200433 - Shanghai/CN



Previous research found that UCA1, a long non-coding RNA, aberrantly expressed and associated with cell proliferation and chemo-resistance in many cancers. The aim of this study was to investigate the role of UCA1 in acquired resistance of EGFR-TKIs in NSCLC.


UCA1 expression level was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in NSCLC cell lines or tumor tissues. Si-RNA was used to downregulate the expression of UCA1. The effect of UCA1 on cell proliferation and apoptosis was undergone by CCK-8 and flow cytometry assays. The expression of proteins was determined by western blot and immunohistochemistry (IHC) analysis. The gefitinib-resistant PC9/R xenograft tumor models were used to validate the effect of UCA1 in vivo.


UCA1 was significantly up-regulated in gefitinib-resistant cells PC9/R and H1975 compared with gefitinib-sensitive PC9 cells. By silencing UCA1, the gefitinib sensitivity was partly restored in PC9/R,but this change in sensitivity was not observed in H1975. Inhibiting UCA1 induced cell apoptosis in PC9/R, and significantly restrained tumor growth in nude mice, compared with control group (P < 0.01). The expression of pEGFR, pAKT, pERK and pmTOR was down-regulated by silencing UCA1 in PC9/R. In clinical setting, we detected the expression of UCA1 in EGFR-mutant NSCLC patients, including before starting EGFR-TKIs treatment (n = 74) and another at the presentation of acquired resistance (n = 48). UCA1 expression level after development of acquired resistance to EGFR-TKIs was significantly higher than at sensitivity (1.9 ± 0.05 vs 0.4 ± 0.12, P = 0.0024). We divided the 74 patients into a high UCA1 expression group (n = 24) and a low group (n = 50), according to a UCA1/GAPDH ratio of 0.068 (median level) in EGFR-TKIs sensitive tissues. The objective response rate in high UCA1 expression group was significantly lower than the low expression group (P = 0.007). High expression of UCA1 was associated with a shorter progression free survival(P < 0.01).


UCA1 could regulate cell proliferation and apoptosis through activating PI3K/AKT/mTOR pathway, and its over-expression was associated with acquired resistance of EGFR-TKIs both in cell lines and clinical samples, which suggest that UCA1 might be act as a biomarker to predict the acquired resistance of EGFR-TKIs.


All authors have declared no conflicts of interest.