Hilal Ozakinci MD , Aileen Y. Alontaga PhD , Pedro Cano MD , John M. Koomen PhD , Bradford A. Perez MD , Amer A. Beg PhD , Alberto A. Chiappori MD , Eric B. Haura MD , Theresa A. Boyle MD, PhD
{"title":"Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel","authors":"Hilal Ozakinci MD , Aileen Y. Alontaga PhD , Pedro Cano MD , John M. Koomen PhD , Bradford A. Perez MD , Amer A. Beg PhD , Alberto A. Chiappori MD , Eric B. Haura MD , Theresa A. Boyle MD, PhD","doi":"10.1016/j.jtocrr.2024.100723","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>ASCL1</em>, <em>NEUROD1</em>, <em>POU2F3</em>, and <em>YAP1</em> 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).</div></div><div><h3>Results</h3><div>The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was <em>ASCL1</em> in 74.2% of the samples, <em>NEUROD1</em> in 20%, and <em>POU2F3</em> in 2.9%. The <em>ASCL1</em>, <em>NEUROD1</em>, and <em>POU2F3</em> gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes <em>DLL3</em>, <em>EZH2</em>, <em>TERT</em>, and <em>RET</em>. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of <em>HLA</em> genes, immune cell, and immune checkpoint genes, except the <em>LAG3</em> gene.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100723"},"PeriodicalIF":3.0000,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JTO Clinical and Research Reports","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666364324000936","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.