Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer.
Effect of mesenchymal-epithelial transition amplification on immune microenvironment and efficacy of immune checkpoint inhibitors in patients with non-small cell lung cancer.
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间充质-上皮转化扩增对非小细胞肺癌患者免疫微环境的影响及免疫检查点抑制剂的疗效。
DOI：
10.21037/atm-21-4543
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发表时间：
2021-09
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Su S;Lin A;Luo P;Zou J;Huang Z;Wang X;Zeng Y;Cen W;Zhang X;Huang H;Hu J;Zhang J
免疫检查点抑制剂（ICI）为各种组织学类型的肺癌患者带来了临床益处。先前的研究已经表明间充质-上皮转化（MET）与非小细胞肺癌（NSCLC）的免疫治疗反应之间存在相关性，但缺乏MET扩增与NSCLC ICI反应相关性的临床数据。收集并汇总了来自两个免疫治疗队列（Rizvi等人的队列和我们当地的队列）的拷贝数变异（CNA）、体细胞突变和临床数据，以进一步研究MET扩增在接受ICI的非小细胞肺癌患者中的关键作用。在癌症基因组图谱（TCGA）-NSCLC [肺腺癌（LUAD）/肺鳞状细胞癌（LUSC）]数据集中进一步研究了MET扩增与肿瘤免疫原性和抗肿瘤免疫力之间的相关性。在免疫治疗队列中，MET扩增与接受ICI治疗的患者的无进展生存期（PFS）时间延长相关（P=0.039; HR =0.37; 95% CI：0.18-0.73）。在TCGA-NSCLC数据集中，MET扩增与高MET mRNA和蛋白水平、肿瘤突变负荷（TMB）、新抗原负荷（NAL）、免疫激活细胞模式、免疫相关基因表达水平以及DNA损伤反应和修复（DDR）途径中的基因改变数量相关。基因集富集分析（GSEA）结果表明MET扩增组中免疫应答相关途径的显著上调。我们的研究结果表明，MET扩增可能是NSCLC免疫治疗疗效的一种新的预测标志物。
Immune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in non-small cell lung cancer (NSCLC) but there is a lack of clinical data on the correlation of MET amplification with the ICI response in NSCLC. Copy number alteration (CNA), somatic mutation, and clinical data from two immunotherapy cohorts (Rizvi et al. cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC [lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)] data-set. In the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039; HR =0.37; 95% CI: 0.18–0.73). In the TCGA-NSCLC data-set, MET amplification was associated with high MET mRNA and protein levels, tumor mutation burden (TMB), neoantigen load (NAL), immune-activated cell patterns, immune-related gene expression levels, and the number of gene alterations in the DNA damage response and repair (DDR) pathway. Gene set enrichment analysis (GSEA) results indicated significant up-regulation of the immune response-related pathways in the MET-amplification group. Our results suggest that MET amplification may be a novel predictive marker for immunotherapy efficacy in NSCLC.
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影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
DOI：
10.1126/science.aaf1490
发表时间：
2016-03-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
McGranahan N;Furness AJ;Rosenthal R;Ramskov S;Lyngaa R;Saini SK;Jamal-Hanjani M;Wilson GA;Birkbak NJ;Hiley CT;Watkins TB;Shafi S;Murugaesu N;Mitter R;Akarca AU;Linares J;Marafioti T;Henry JY;Van Allen EM;Miao D;Schilling B;Schadendorf D;Garraway LA;Makarov V;Rizvi NA;Snyder A;Hellmann MD;Merghoub T;Wolchok JD;Shukla SA;Wu CJ;Peggs KS;Chan TA;Hadrup SR;Quezada SA;Swanton C
通讯作者：
Swanton C
DOI：
10.1126/science.aar3593
发表时间：
2018-10-12
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cristescu R;Mogg R;Ayers M;Albright A;Murphy E;Yearley J;Sher X;Liu XQ;Lu H;Nebozhyn M;Zhang C;Lunceford JK;Joe A;Cheng J;Webber AL;Ibrahim N;Plimack ER;Ott PA;Seiwert TY;Ribas A;McClanahan TK;Tomassini JE;Loboda A;Kaufman D
通讯作者：
Kaufman D
影响因子：
20.4
作者：
Park, Sehhoon;Lee, Hayoon;Park, Keunchil
通讯作者：
Park, Keunchil