Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Thorac Cancer. 2021 Jan;12(1):40-47. doi: 10.1111/1759-7714.13705. Epub 2020 Nov 15.
Small cell lung cancer (SCLC) is one of the most aggressive lung cancers. Treatment of SCLC has remained unchanged during the past decades. Preclinical studies have revealed ASCL1 as a transcription regulator in the neuroendocrine (NE) differentiation and carcinogenesis of SCLC. However, there are few studies on correlation of ASCL1 expression and clinicopathological factors in resected SCLCs. Here, we aimed to analyze the ASCL1 expression of SCLC and investigate its associations with clinicopathological factors and survival.
A total of 247 surgically resected pure SCLC specimens were included in this retrospective study, all of which were processed using tissue microarrays for immunohistochemistry analysis of ASCL1. A total of 48 of 247 cases were tested by NanoString for mRNA expression analysis on 50 SCLC related genes. Statistical analysis was performed using R studio and SPSS software.
NE scores of 48 pure SCLC specimens were calculated by analyzing 50 preselected genes. A significant correlation between NE score with both ASCL1 mRNA expression and ASCL1 protein expression were observed. For the entire cohort of 247 patients, ASCL1 was highly expressed in 42.5% of pure SCLC patients according to IHC results. Significant differences were observed between ASCL1 high and low expression groups in variables including staging, lymph node metastasis, nerve invasion and overall survival.
In limited staged pure SCLC, ASCL1 expression was positively correlated with NE signature, pTNM stage, nerve invasion and OS. ASCL1 may therefore serve as a potential biomarker to predict prognosis as well as in the selection of patients for therapies targeting ASCL1-regulated downstream molecules.
小细胞肺癌（SCLC）是最具侵袭性的肺癌之一。在过去的几十年中，SCLC 的治疗方法一直没有改变。临床前研究表明 ASCL1 是 SCLC 神经内分泌（NE）分化和癌变的转录调节剂。然而，关于 ASCL1 表达与 SCLC 切除后临床病理因素的相关性研究较少。在这里，我们旨在分析 SCLC 中 ASCL1 的表达，并探讨其与临床病理因素和生存的关系。
本回顾性研究共纳入 247 例手术切除的纯 SCLC 标本，均采用组织微阵列进行 ASCL1 免疫组织化学分析。其中 48 例采用 NanoString 对 50 个与 SCLC 相关的基因进行 mRNA 表达分析。统计分析采用 R studio 和 SPSS 软件进行。
通过分析 50 个预选基因，计算了 48 例纯 SCLC 标本的 NE 评分。ASCL1 mRNA 表达和 ASCL1 蛋白表达与 NE 评分均呈显著正相关。在 247 例患者的整个队列中，根据 IHC 结果，42.5%的纯 SCLC 患者 ASCL1 高表达。在分期、淋巴结转移、神经侵犯和总生存等变量方面，ASCL1 高表达组和低表达组之间存在显著差异。
在有限分期的纯 SCLC 中，ASCL1 表达与 NE 特征、pTNM 分期、神经侵犯和 OS 呈正相关。因此，ASCL1 可能作为一种潜在的生物标志物，用于预测预后以及选择针对 ASCL1 调节的下游分子的治疗。
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