Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel

IF 3 Q2 ONCOLOGY
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引用次数: 0

Abstract

Introduction

The translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers.

Methods

RNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the ASCL1, NEUROD1, POU2F3, and YAP1 genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25).

Results

The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was ASCL1 in 74.2% of the samples, NEUROD1 in 20%, and POU2F3 in 2.9%. The ASCL1, NEUROD1, and POU2F3 gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes DLL3, EZH2, TERT, and RET. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of HLA genes, immune cell, and immune checkpoint genes, except the LAG3 gene.

Conclusions

Clinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.
用临床 RNA 表达面板揭示 SCLC 的分子特征
导言:SCLC 的基因表达谱在临床检测中的应用相对来说仍有待探索。本研究评估了SCLC中的基因表达变异,以确定潜在的生物标记物。方法使用经临床验证的RNA Salah靶向表达面板(RNA STEP)对35名确诊为SCLC患者的44个肿瘤样本进行了RNA表达谱分析。对两个不同的SCLC队列进行了RNA测序(RNA-Seq)和免疫组化,并对ASCL1、NEUROD1、POU2F3和YAP1基因及其相应蛋白进行了相关性分析。对 RNA STEP 和 RNA-Seq 结果进行了评估,以了解 SCLC 原发部位和转移部位之间的基因表达谱和异质性。将独立 SCLC 样本(n = 35)的 RNA STEP 基因表达谱与肺腺癌(n = 160)和鳞状细胞癌(n = 25)的结果进行了比较。74.2% 的样本中,RNA STEP 的主导转录调节因子是 ASCL1,20% 是 NEUROD1,2.9% 是 POU2F3。ASCL1、NEUROD1和POU2F3基因的表达谱在原发部位和转移部位之间存在差异。SCLCs的靶向基因DLL3、EZH2、TERT和RET的表达明显较高。与肺腺癌和鳞状细胞癌相比,SCLC 的免疫特征相对较低,HLA 基因、免疫细胞和免疫检查点基因(LAG3 基因除外)的表达较低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
4.20
自引率
0.00%
发文量
145
审稿时长
19 weeks
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