Abstract 30P
Background
Small cell lung cancer (SCLC) is a highly aggressive malignancy prone to early recurrence and metastasis. Preclinical studies have found that Hes1, as a transcription repressor of the basic helix-loop-helix (BHLH) family, can not only prevent the proliferation and migration of SCLC tumor cells, but also inhibit the neuroendocrine transcription factor ASCL1. However, the prognostic implication of Hes1 protein on surgically resected SCLCs remains unclear. The current study aims to analyze the expression pattern and prognostic value of Hes1 protein in SCLC.
Methods
Two hundred and forty seven surgically resected pure SCLC specimens were reviewed and included in this study by using tissue microarrays (TMA) for immunohistochemistry(IHC)analysis of Hes1 protein on a fully automatic Roche immunohistochemical instruments. And the corresponding clinicopathological features such as age, lymph node metastasis, major cell shape and tumor infiltrating lymphocytes (TILs), etc were reviewed and collected. Correlation analysis of Hes1 protein with clinic pathological features and survival analysis was performed using SPSS 25.0 and Graphpad Prism 5.0 software.
Results
Among the 247 surgically resected pure SCLC patients, 175 (71%) were male and 202 (82%) were less than 65 years. According to the AJCC Cancer Staging Manual (seventh edition), 78 (31.6%) were stage I, 68 (27.5%) were stage II, and 101 (40.9%) were stage III. Hes1 expression was localized in the nucleus of SCLC tumor cells. A total of 129 of the 247 enrolled SCLC patients showed high expression of Hes1 with a positive rate of 52.2% (129/247), and was found positively correlated with a lower age(≤65 yrs., p=0.014), no lymph node metastasis(P=0.003), main cell morphology of round cells(p=0.002), and TILs≤30% (p=0.010). Univariate survival analysis revealed a favorable survival in high expression group for a significant disease free survival (DFS, HR=1.477,95%CI 1.025-2.129, P=0.036) and a positive trend of overall survival (OS, HR=1.181,95%CI 0.778-1.792, P=0.435).
Conclusions
In limited stage pure small cell lung cancer, high expression of Hes1 protein is related to age, lymph node metastasis, main cell morphology and TILs, which contributes as a potential biomarker for the prognosis of SCLC patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Cancer Foundation of China, Beijing Hope Marathon Foundation [grant number LC2017A20] and the National Key Research and Development Program of China [grant numbers 2017YFC1308704, 2017YFC1311000 and 2017YFC1308700] and CAMS Innovation Fund for Medical Sciences[grant number 2021-I2M C&T-B-062]. Medical Sciences[grant number 2021-I2M C&T-B-062]. the Cancer Foundation of China, Beijing Hope Marathon Foundation [grant number LC2017A20] and the Na tional Key Research and Development Program of China [grant numbers 2017YFC1308704, 2017YFC1311000 and 2017YFC1308700] and CAMS Innovation Fund for Medical Sciences[grant number 2021-I2M C&T-B-062].
Disclosure
All authors have declared no conflicts of interest.