ASCL1 and DLL3 expressions and their clinicopathological implications in surgically resected pure small cell lung cancer: A study of 247 cases from the National Cancer Center of China

手术切除的纯小细胞肺癌中 ASCL1 和 DLL3 的表达及其临床病理意义:中国国家癌症中心 247 例病例的研究

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作者:Chunfang Hu, Jiyan Dong, Li Liu, Jingbo Liu, Xujie Sun, Fei Teng, Xin Wang, Jianming Ying, Junling Li, Puyuan Xing, Lin Yang

Conclusion

ASCL1 and DLL3 were highly expressed in SCLC tumor samples, and a positive correlation between these two markers was observed. Co-analysis of ASCL1 and DLL3 may identify a distinct SCLC subgroup benefit from targeted therapy. Therefore, ASCL1 and DLL3 could be potential biomarkers served for the selection of related patients.

Methods

A total of 247 surgically resected pure SCLC samples with limited clinical stage and follow-up data were retrieved in this retrospective study. ASCL1 and DLL3 protein expression was detected by immunohistochemistry staining. The correlations between ASCL1 and DLL3 expressions, as well as their clinicopathological features, were analyzed by χ2 tests. Disease-free survival (DFS) and overall survival (OS) in SCLC patients with ASCL1/DLL3 low and high expressions were compared by the Kaplan-Meier method and log-rank tests.

Objective

Small cell lung cancer (SCLC) is one of the most aggressive malignancies characterized by neuroendocrine (NE) differentiation. The Delta-like protein 3 (DLL3), as a direct downstream target of ASCL1, is involved in NE differentiation and carcinogenesis of SCLC. This study aims to investigate the relationship between ASCL1 and DLL3 expressions and their clinicopathological implications in SCLC.

Results

ASCL1 high expression was detected in 105 (42.5%) patients. Its expression was positively correlated with the clinical stage (p = 0.02) and nerve invasion (p = 0.03). DLL3 high expression was observed in 188 (72.8%) patients and was correlated with vascular invasion (p = 0.04). ASCL1 expression was positively associated with DLL3 expression (p = 0.03). In addition, DLL3 expression has a strong correlation with the expression of thyroid transcription factor-1 (TTF1) and conventional NE markers.

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