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浸润前和早期浸润性肺腺癌的基因组表观和免疫微环境特征

已有 140 次阅读2021-1-27 15:40 |个人分类:TET学习|系统分类:医学科学| 肺癌

浸润前和早期浸润性肺腺癌的基因组表观和免疫微环境特征。Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma
背景:了解浸润前和早期浸润性肺腺癌的基因组结构和免疫微环境特征,可能为早期发现和干预提供重要的信息和帮助。
Background:Understanding the genomic landscape and immune microenvironment features of preinvasive and early invasive lung adenocarcinoma may provide critical insight and facilitate development of novel strategies for early detection and intervention.

方法:对30例原位腺癌(AIS)患者(n=8)、微浸润癌(MIA)患者(n=8)的80例肿瘤组织和30例配对正常肺组织标本进行分析,对14例浸润性腺癌(IAC)进行CD8和程序性死亡配体1(PD-L1)的多区全外显子组测序和免疫组化染色。
Methods:A total of 80 tumor tissue samples and 30 paired histologically normal lung tissue samples from 30 patients with adenocarcinoma in situ (AIS) (n = 8), minimally invasive adenocarcinoma (MIA) (n = 8), and invasive adenocarcinoma (IAC) (n = 14) were subjected to multiregion whole exome sequencing and immunohistochemistry staining for CD8 and programmed death ligand 1 (PD-L1).

结果:包括AIS在内的所有肿瘤均表现出基因组异质性。EGFR、erb-b2受体酪氨酸激酶2基因(ERBB2)、NRAS和BRAF中的典型癌基因突变仅在每个肿瘤的所有区域检测到主干突变,而与细胞迁移、缝隙连接和转移相关的基因均为亚克隆突变。EGFR突变是AIS、MIA和IAC中最常见的驱动因素改变,而肿瘤蛋白p53基因(TP53)在MIA和IAC中发现,但在AIS中没有发现。AIS、MIA和IAC中PD-L1的表达无差异,但IAC中CD8的阳性率较高。PD-L1和CD8均阳性的肿瘤有较大比例的亚克隆突变。
Results: All tumors, including AIS, exhibited evidence of genomic intratumor heterogeneity. Canonical cancer gene mutations in EGFR, erb-b2 receptor tyrosine kinase 2 gene (ERBB2), 
NRAS, and BRAF were exclusively trunk mutations detected in all regions within each tumor, whereas genes associated with cell mobility, gap junction, and metastasis were all subclonal mutations. EGFR mutation represented the most common driver alterations across AIS, MIA, and IAC, whereas tumor protein p53 gene (TP53) was identified in MIA and IAC but not in AIS. There was no difference in PD-L1 e.xpression among AIS, MIA, and IAC, but the CD8 positivity rate was higher in IAC. Tumors positive for both PD-L1 and CD8 had a larger proportion of subclonal mutations.

结论:EGFR、ERBB2、NRAS和BRAF突变是肺腺癌发生过程中的早期克隆基因组事件,而TP53和细胞迁移、缝隙连接和转移相关基因可能是与亚克隆多样化和肿瘤进展相关的晚期事件。基因组肿瘤内异质性和免疫编辑是常见的和早期的现象,可能发生在获得浸润之前
Conclusions:Mutations in EGFR, ERBB2, NRAS, and BRAF are early clonal genomic events during carcinogenesis of lung adenocarcinoma, whereas TP53 and cell mobility, gap junction, and metastasis-related genes may be late events associated with subclonal diversification and neoplastic progression. Genomic intratumor heterogeneity and immunoediting are common and early phenomena that may have occurred before the acquisition of invasion.

图1.不同亚型肺腺癌(LUAD)的临床病理特征。(A) 三种典型病理亚型的病理及相应影像学表现。红色箭头表示病变。
Figure 1. Clinicopathologic characteristics among different subtypes of lung adenocarcinoma (LUAD). (A) Pathological and corresponding radiological images of three representative pathological subtypes. Red arrow indicates the annotation of the lesion.

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回复 hyc3140 2021-1-27 17:10
Zhang C, et al. Genomic Landscape and Immune Microenvironment Features of Preinvasive and Early Invasive Lung Adenocarcinoma. J Thorac Oncol. 2019 Nov;14(11):1912-1923. PMID: 31446140

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