干旱区生态环境知识资源中心(Arid): Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers

Arid

DOI	10.1016/j.jtho.2021.08.763
	Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers
	Qu, Song; Fetsch, Patricia; Thomas, Anish; Pommier, Yves; Schrump, David S.; Miettinen, Markku M.; Chen, Haobin
通讯作者	Chen, HB (corresponding author)，NCI, Thorac Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 3-5888, Bethesda, MD 20892 USA.
来源期刊	JOURNAL OF THORACIC ONCOLOGY
ISSN	1556-0864
EISSN	1556-1380
出版年	2022
卷号	17 期号:1
英文摘要	Introduction: A new molecular subtype classification was recently proposed for SCLC. It is necessary to validate it in primary SCLC tumors by immunohistochemical (IHC) staining and define its clinical relevance. Methods: We used IHC to assess four subtype markers (ASCL1, NEUROD1, POU2F3, and YAP1) in 194 cores from 146 primary SCLC tumors. The profiles of tumor-associated CD3 thorn and CD8 thorn T-cells, MYC paralogs, SLFN11, and SYP were compared among different subtypes. Validation was performed using publicly available RNA sequencing data of SCLC. Results: ASCL1, NEUROD1, POU2F3, and YAP1 were the dominant molecular subtypes in 78.2%, 5.6%, 7%, and 2.8% of the tumors, respectively; 6.3% of the tumors were negative for all four subtype markers. Notably, three cases were uniquely positive for YAP1. Substantial intratumoral heterogeneity was observed, with 17.6% and 2.8% of the tumors being positive for two and three subtype markers, respectively. The non-ASCL1/NEUROD1 tumors had more CD8 thorn T-cells and manifested more frequently an inflamed immunophenotype. L-MYC and MYC were more often associated with ASCL1/NEUROD1 subtypes and nonASCL1/NEUROD1 subtypes, respectively. SLFN11 expression was absent in 40% of the tumors, especially those negative for the four subtype markers. SYP was often expressed in the ASCL1 and NEUROD1 subtypes and was associated with less tumor-associated CD8 thorn T-cells and a desert immunophenotype. Conclusions: We validated the new molecular subtype classification in primary SCLC tumors by IHC and identified several intriguing associations between subtypes and therapeutic markers. The new subtype classification may potentially assist treatment decisions in SCLC. Published by Elsevier Inc. on behalf of International Association for the Study of Lung Cancer.
英文关键词	CD8(+) T-cells Intratumoral heterogeneity MYC L-MYC SLFN11 Synaptophysin
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:000736948100017
WOS关键词	CELL LUNG-CANCER ; GENE COPY NUMBER ; PROTEIN EXPRESSION ; YAP1 ; IDENTIFICATION ; HETEROGENEITY ; CISPLATIN ; NEUROD1 ; BIOLOGY ; MODELS
WOS类目	Oncology ; Respiratory System
WOS研究方向	Oncology ; Respiratory System
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/376902
作者单位	[Qu, Song] NIH, Dept Lab Med, Clin Ctr, Bldg 10, Bethesda, MD 20892 USA; [Fetsch, Patricia; Miettinen, Markku M.] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA; [Thomas, Anish; Pommier, Yves] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA; [Schrump, David S.; Chen, Haobin] NCI, Thorac Surg Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 3-5888, Bethesda, MD 20892 USA
推荐引用方式 GB/T 7714	Qu, Song,Fetsch, Patricia,Thomas, Anish,et al. Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers[J],2022,17(1).
APA	Qu, Song.,Fetsch, Patricia.,Thomas, Anish.,Pommier, Yves.,Schrump, David S..,...&Chen, Haobin.(2022).Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers.JOURNAL OF THORACIC ONCOLOGY,17(1).
MLA	Qu, Song,et al."Molecular Subtypes of Primary SCLC Tumors and Their Associations With Neuroendocrine and Therapeutic Markers".JOURNAL OF THORACIC ONCOLOGY 17.1(2022).