Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma.
Single-cell transcriptome analysis demonstrates inter-patient and intra-tumor heterogeneity in primary and metastatic lung adenocarcinoma.
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单细胞转录组分析证明原发性和转移性肺腺癌患者间和肿瘤内的异质性。
DOI：
10.18632/aging.103945
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发表时间：
2020-11-10
期刊：
影响因子：
--
通讯作者：
Qi Y
中科院分区：
文献类型：
--
作者：
Liu Y;Ye G;Huang L;Zhang C;Sheng Y;Wu B;Han L;Wu C;Dong B;Qi Y
在这项研究中，我们对来自GSE123902和GSE131907数据集的50例原发性和转移性肺腺癌（LUAD）样本进行了单细胞转录组数据分析，以确定患者间和肿瘤内异质性的情况。在原发性和转移性LUAD样本中，基因表达谱和拷贝数变异（CNV）显示出显著的异质性。我们观察到，与原发肿瘤样本相比，脑转移样本中与翻译起始、内质网应激、外泌体和未折叠蛋白反应相关的通路上调。与未治疗的LUAD患者相比，化疗治疗的LUAD患者脑转移样本中与外泌体、细胞粘附和代谢相关的途径上调，上皮-间质转化（EMT）途径下调。脑转移样本中的肿瘤细胞亚群显示出与II型肺泡细胞、化疗耐药、糖酵解和氧化磷酸化（代谢重编程）以及EMT相关基因的差异表达。因此，单细胞转录组分析表明，在原发性和转移性LUAD组织中，与肿瘤进展、化疗耐药和代谢相关的通路调节在患者内部和肿瘤内部存在异质性。此外，我们的研究表明，单细胞转录组分析是准确诊断和个性化靶向治疗LUAD患者的潜在有用工具。
In this study, we performed single-cell transcriptome data analysis of fifty primary and metastatic lung adenocarcinoma (LUAD) samples from the GSE123902 and GSE131907 datasets to determine the landscape of inter-patient and intra-tumoral heterogeneity. The gene expression profiles and copy number variations (CNV) showed significant heterogeneity in the primary and metastatic LUAD samples. We observed upregulation of pathways related to translational initiation, endoplasmic reticulum stress, exosomes, and unfolded protein response in the brain metastasis samples as compared to the primary tumor samples. Pathways related to exosomes, cell adhesion and metabolism were upregulated and the epithelial-to-mesenchymal-transition (EMT) pathway was downregulated in brain metastasis samples from chemotherapy-treated LUAD patients as compared to those from the untreated LUAD patients. Tumor cell subgroups in the brain metastasis samples showed differential expression of genes related to type II alveolar cells, chemoresistance, glycolysis and oxidative phosphorylation (metabolic reprogramming), and EMT. Thus, single-cell transcriptome analysis demonstrated intra-patient and intra-tumor heterogeneity in the regulation of pathways related to tumor progression, chemoresistance and metabolism in the primary and metastatic LUAD tissues. Moreover, our study demonstrates that single cell transcriptome analysis is a potentially useful tool for accurate diagnosis and personalized targeted treatment of LUAD patients.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
DOI：
10.1158/1078-0432.ccr-13-0623
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dennison JB;Molina JR;Mitra S;González-Angulo AM;Balko JM;Kuba MG;Sanders ME;Pinto JA;Gómez HL;Arteaga CL;Brown RE;Mills GB
通讯作者：
Mills GB
影响因子：
20.4
作者：
Caiola, Elisa;Iezzi, Alice;Marabese, Mirko
通讯作者：
Marabese, Mirko
影响因子：
3.4
作者：
Emmanouilidi, Aikaterini;Paladin, Dino;Falasca, Marco
通讯作者：
Falasca, Marco
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D