Molecular characteristics of primary pulmonary lymphoepithelioma-like carcinoma based on integrated genomic analyses.
Molecular characteristics of primary pulmonary lymphoepithelioma-like carcinoma based on integrated genomic analyses.
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基于整合基因组分析的原发性肺淋巴上皮瘤样癌的分子特征
DOI：
10.1038/s41392-020-00382-6
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发表时间：
2021-01-08
影响因子：
39.3
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Chen B;Zhang Y;Dai S;Zhou P;Luo W;Wang Z;Chen X;Cheng P;Zheng G;Ren J;Yang X;Li W
原发性肺淋巴上皮瘤样癌（pLELC）是一种罕见的非小细胞肺癌（NSCLC）亚型。我们之前的报告已描述了其临床特征，但分子特征仍不清楚。在此，我们对pLELC的基因组特征进行了探究。在41574例肺癌中，纳入了128例pLELC和162例非pLELC的NSCLC。通过免疫组化检测在47例手术切除的pLELC样本中检测程序性细胞死亡配体1（PD - L1）和p53蛋白的表达。对8例冷冻的pLELC组织进行了多组学基因组分析，包括全基因组测序（WGS）、RNA全转录组测序（RNA - seq）和爱泼斯坦 - 巴尔病毒（EBV）整合分析，并与来自癌症基因组图谱（TCGA）的50例肺腺癌（LUAD）和50例肺鳞状细胞癌（LUSC）以及另外26例EBV阳性鼻咽癌（EBV + - NPC）进行比较。pLELC患者的无进展生存期（PFS）和总生存期（OS）优于非pLELC患者。高PD - L1或p53表达与延长的无病生存期（DFS）相关。pLELC有14个频繁突变基因（FMG）。发现了体细胞突变基因和基因损伤的富集情况，这与在LUAD、LUSC和EBV + -鼻咽癌（NPC）中的观察结果不同。三个肿瘤相关基因，含锌指和BTB结构域蛋白16（ZBTB16）、过氧化物酶体增殖物激活受体γ（PPARG）和转化生长因子β受体2（TGFBR2）因拷贝数变异（CNV）缺失而下调。EBV易于整合到基因间和内含子区域，伴有两个上调的miR - BamH1 - A正向转录本（BARTs），即BART5 - 3P和BART20 - 3P。我们的研究结果表明，pLELC具有独特的基因组特征。三个因CNV缺失的肿瘤相关基因和两个miR - BARTs可能参与pLELC的肿瘤发生。
Primary pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare non-small cell lung cancer (NSCLC) subtype. Clinical features have been described in our previous report, but molecular characteristics remain unclear. Herein, pLELC genomic features were explored. Among 41,574 lung cancers, 128 pLELCs and 162 non-pLELC NSCLCs were enrolled. Programmed cell death ligand 1 (PD-L1) and protein 53 (p53) expression was detected in 47 surgically resected pLELC samples by immunohistochemical assays. Multiomics genomic analyses, including whole-genome sequencing (WGS), RNA whole-transcriptome sequencing (RNA-seq), and Epstein-Barr virus (EBV) integration analyses, were performed on eight frozen pLELC tissues and compared with 50 lung adenocarcinomas (LUADs) and 50 lung squamous cell carcinomas (LUSCs) from The Cancer Genome Atlas (TCGA) and another 26 EBV-positive nasopharynx cancers (EBV+-NPCs). Progression-free survival (PFS) and overall survival (OS) of pLELC patients were better than those of non-pLELC patients. High PD-L1 or p53 expression was associated with extended disease-free survival (DFS). pLELC had 14 frequently mutated genes (FMGs). Somatically mutated genes and enrichment of genetic lesions were found, which differed from observations in LUAD, LUSC, and EBV+-nasopharyngeal carcinoma (NPC). Three tumor-associated genes, zinc finger and BTB domain-containing 16 (ZBTB16), peroxisome proliferator activated receptor gamma (PPARG), and transforming growth factor beta receptor 2 (TGFBR2), were downregulated with copy number variation (CNV) loss. EBV was prone to integrating into intergenic and intronic regions with two upregulated miR-BamH1-A rightward transcripts (BARTs),BART5-3PandBART20-3P. Our findings reveal that pLELC has a distinct genomic signature. Three tumor-associated genes with CNV loss and two miR-BARTs might be involved in pLELC tumorigenesis.
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影响因子：
--
作者：
Fang W;Hong S;Chen N;He X;Zhan J;Qin T;Zhou T;Hu Z;Ma Y;Zhao Y;Tian Y;Yang Y;Xue C;Tang Y;Huang Y;Zhao H;Zhang L
通讯作者：
Zhang L
影响因子：
5.2
作者：
Chau, Shuk-Ling;Tong, Joanna Hung-Man;To, Ka-Fai
通讯作者：
To, Ka-Fai
DOI：
10.1002/hed.25544
发表时间：
2019-03-01
影响因子：
2.9
作者：
Gao, Wei;Wong, Thian-Sze;Chan, Jimmy Yu-Wai
通讯作者：
Chan, Jimmy Yu-Wai
影响因子：
14.9
作者：
Forbes, Simon A.;Tang, Gurpreet;Futreal, P. Andrew
通讯作者：
Futreal, P. Andrew
DOI：
10.1002/path.5018
发表时间：
2018-04
期刊：
The Journal of pathology
影响因子：
--
作者：
Lung RW;Hau PM;Yu KH;Yip KY;Tong JH;Chak WP;Chan AW;Lam KH;Lo AK;Tin EK;Chau SL;Pang JC;Kwan JS;Busson P;Young LS;Yap LF;Tsao SW;To KF;Lo KW
通讯作者：
Lo KW