干旱区生态环境知识资源中心(Arid): Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases

Arid

DOI	10.21037/tlcr.2019.11.30
	Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases
	Lohinai, Zoltan 1; Megyesfalvi, Zsolt 1,2,3,4; Suda, Kenichi 5; Harko, Tunde 6; Ren, Shengxiang 7; Moldvay, Judit 1; Laszlo, Viktoria 1,4; Rivard, Christopher 8; Dome, Balazs 1,2,3,4; Hirsch, Fred R.8,9
通讯作者	Lohinai, Zoltan ; Dome, Balazs
来源期刊	TRANSLATIONAL LUNG CANCER RESEARCH
ISSN	2218-6751
EISSN	2226-4477
出版年	2019
卷号	8 期号:6 页码:938-+
英文摘要	Background: Recent preclinical data suggest that neuroendocrine (NE) subtype of small cell lung cancer (SCLC) has strong therapeutic relevance. NE high tumors are associated with immune desert and NE low tumors are considered to have an immune oasis phenotype. Our aim was to investigate the NE phenotypes of surgically resected SCLC tumors according to inter-tumor heterogeneity. Methods: Expression analysis for 2,560 genes was performed in 32 surgically resected SCLC patients' primary tumors and corresponding lymph node (LN) metastases. To analyze tumor heterogeneity, we examined the differences in the gene expression of primary tumors versus LN metastases. We performed cluster analysis and heat map to divide patients into NE high and low subtypes by using the top NE-associated genes described in predinical studies. Results: We found 6% (n=154) genes with significant differences and only 13.1% (n=336) of all genes in the panel had a strong correlation between the primary tumor and LN metastases. Cluster analysis clearly distinguished SCLC NE high versus low subtypes both in primary tumor (20 vs. 12, respectively) and LNs (23 vs. 9, respectively). As for inter-tumor heterogeneity, in case of five patients, a change in the NE pattern was observed. Specifically, we found significant downregulation of the NE-associated genes C4V1 (P=0.004), CAV2 (P=0.029) and ANXA3 (P=0.035) in their LN metastases compared to their primary tumor. Conclusions: Our data confirm the results of preclinical studies and clearly distinguish NE low and high differentiation clusters in SCLC. Moreover, they highlight the gene expression discordance between primary tumors and corresponding LN metastases suggesting that the NE pattern of metastatic LNs might not reflect that of the primary tumor. Altogether, by shedding light on the diversity of SCLC, the current study might help to improve patient selection and treatment in this devastating disease.
英文关键词	Small cell lung cancer (SCLC) neuroendocrine tumor lymph node metastasis tumor heterogeneity RNA sequencing
类型	Article
语种	英语
国家	Hungary ; Austria ; Japan ; Peoples R China ; USA
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000505217600020
WOS关键词	CANCER ; HETEROGENEITY
WOS类目	Oncology ; Respiratory System
WOS研究方向	Oncology ; Respiratory System
EI主题词	2019-12-01
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/311126
作者单位	1.Natl Koranyi Inst Pulmonol, Dept Tumor Biol, Piheno Ut 1, H-1121 Budapest, Hungary; 2.Semmelweis Univ, Dept Thorac Surg, Budapest, Hungary; 3.Natl Inst Oncol, Budapest, Hungary; 4.Med Univ Vienna, Dept Surg, Div Thorac Surg, Waehringer Guertel 18-20, A-1090 Vienna, Austria; 5.Kindai Univ, Fac Med, Dept Surg, Div Thorac Surg, Osaka, Japan; 6.Natl Koranyi Inst Pulmonol, Dept Pathol, Budapest, Hungary; 7.Tongji Univ, Shanghai Pulm Hosp, Dept Med Oncol, Shanghai 200433, Peoples R China; 8.Univ Colorado, Div Med Oncol, Anschutz Med Campus, Aurora, CO USA; 9.Mt Sinai Hlth Syst, Tisch Canc Inst, Ctr Thorac Oncol, New York, NY USA
推荐引用方式 GB/T 7714	Lohinai, Zoltan,Megyesfalvi, Zsolt,Suda, Kenichi,et al. Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases[J],2019,8(6):938-+.
APA	Lohinai, Zoltan.,Megyesfalvi, Zsolt.,Suda, Kenichi.,Harko, Tunde.,Ren, Shengxiang.,...&Hirsch, Fred R..(2019).Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases.TRANSLATIONAL LUNG CANCER RESEARCH,8(6),938-+.
MLA	Lohinai, Zoltan,et al."Comparative expression analysis in small cell lung carcinoma reveals neuroendocrine pattern change in primary tumor versus lymph node metastases".TRANSLATIONAL LUNG CANCER RESEARCH 8.6(2019):938-+.