3273 - Low expression of Notch1 and combined Notch1/HES1 are associated with adverse survival factor for limited stage small cell lung cancer

Background

Limited stage small cell lung cancer (LS-SCLC) could be potentially curable with chemotherapy and radiation therapy. Notch pathway could be critically implicated with SCLC development, but there are few studies about its expression and clinical implications in SCLC. In this study, we evaluated the expression of Notch1, Notch2, and HES1 in LS-SCLC from clinical tumor tissue and their impact on PFS and OS.

Methods

A total of 75 patients with LS-SCLC, treated between 2010 and 2018, were enrolled, and their retrospective data were analyzed. Notch1, Notch2 and HES1 protein as Notch transcription factor were evaluated by immunohistochemistry. Staining was considered as low expression when 50% or less of the tumor cells expressed Notch1, Notch2, and HES1 with weak intensity.

Results

Among 75 patients, 42 patients (62.7%) received concurrent chemoradiotherapy, and 13 (17.3%) were diagnosed SCLC combined with NSCLC. Notch1, Notch2, and HES1 were identified in 50 (66.7%), 54 (72.0%), 24 (32.0%). There was no correlation of expression between Notch1 and HES1 (P = 0.115). Low expression of Notch1 or Notch2 was not associated with shorter PFS compared to high expression of them (median, 10.0 vs. 14.23, P = 0.172; 9.93 vs. 12.43, P = 0.759). Low expression of HES1 was tended to shorter PFS than high expression (8.40 vs. 13.57, P = 0.068). Low Notch1 expression was significantly associated with poor OS (median, 17.37 vs. 49.83, P = 0.022), but Notch2 and HES1 were not with OS (median; 21.73 vs. 18.40, P = 0.930; 15.37 vs. 27.90, P = 0.076). Of note, combined low expression of Notch1 and HES1 was significantly related with poor OS (median 15.37 vs. 28.63, P = 0.012). Multivariate Cox regression analysis showed that combined low expression Notch1 and HES1 was an independent poor prognostic factor for SCLC (HR = 1.23, P = 0.423).

Conclusions

Despite dramatic response rate of current standard treatment for LS-SCLC, more than half of patients experience failure within 2 years. It is clinically important to previse who the poor responder to the treatment is. In our study, low expression level of Notch1 and combined low expression of Notch1 and HES1 were related to poor overall survival, and these could be used as a prognostic biomarker for LS-SCLC.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.