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Proteogenomic landscape of squamous cell lung cancer.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-08 , DOI: 10.1038/s41467-019-11452-x Paul A Stewart 1, 2 , Eric A Welsh 2 , Robbert J C Slebos 1 , Bin Fang 3 , Victoria Izumi 3 , Matthew Chambers 2 , Guolin Zhang 1 , Ling Cen 2 , Fredrik Pettersson 2 , Yonghong Zhang 2 , Zhihua Chen 2 , Chia-Ho Cheng 2 , Ram Thapa 2 , Zachary Thompson 2 , Katherine M Fellows 1 , Jewel M Francis 1 , James J Saller 4 , Tania Mesa 5 , Chaomei Zhang 5 , Sean Yoder 5 , Gina M DeNicola 6 , Amer A Beg 7 , Theresa A Boyle 4 , Jamie K Teer 8 , Yian Ann Chen 8 , John M Koomen 9 , Steven A Eschrich 8 , Eric B Haura 1
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-08 , DOI: 10.1038/s41467-019-11452-x Paul A Stewart 1, 2 , Eric A Welsh 2 , Robbert J C Slebos 1 , Bin Fang 3 , Victoria Izumi 3 , Matthew Chambers 2 , Guolin Zhang 1 , Ling Cen 2 , Fredrik Pettersson 2 , Yonghong Zhang 2 , Zhihua Chen 2 , Chia-Ho Cheng 2 , Ram Thapa 2 , Zachary Thompson 2 , Katherine M Fellows 1 , Jewel M Francis 1 , James J Saller 4 , Tania Mesa 5 , Chaomei Zhang 5 , Sean Yoder 5 , Gina M DeNicola 6 , Amer A Beg 7 , Theresa A Boyle 4 , Jamie K Teer 8 , Yian Ann Chen 8 , John M Koomen 9 , Steven A Eschrich 8 , Eric B Haura 1
Affiliation
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How genomic and transcriptomic alterations affect the functional proteome in lung cancer is not fully understood. Here, we integrate DNA copy number, somatic mutations, RNA-sequencing, and expression proteomics in a cohort of 108 squamous cell lung cancer (SCC) patients. We identify three proteomic subtypes, two of which (Inflamed, Redox) comprise 87% of tumors. The Inflamed subtype is enriched with neutrophils, B-cells, and monocytes and expresses more PD-1. Redox tumours are enriched for oxidation-reduction and glutathione pathways and harbor more NFE2L2/KEAP1 alterations and copy gain in the 3q2 locus. Proteomic subtypes are not associated with patient survival. However, B-cell-rich tertiary lymph node structures, more common in Inflamed, are associated with better survival. We identify metabolic vulnerabilities (TP63, PSAT1, and TFRC) in Redox. Our work provides a powerful resource for lung SCC biology and suggests therapeutic opportunities based on redox metabolism and immune cell infiltrates.
中文翻译：
鳞状细胞肺癌的蛋白质组学景观。
基因组和转录组改变如何影响肺癌的功能蛋白质组尚未完全了解。在这里，我们整合了108名鳞状细胞肺癌（SCC）患者队列中的DNA拷贝数，体细胞突变，RNA测序和表达蛋白质组学。我们确定了三种蛋白质组学亚型，其中两种（发炎，氧化还原）占87％的肿瘤。炎症亚型富含嗜中性粒细胞，B细胞和单核细胞，并表达更多的PD-1。氧化还原肿瘤富含氧化还原和谷胱甘肽途径，并在3q2位点具有更多NFE2L2 / KEAP1改变和复制增益。蛋白质组亚型与患者生存率无关。然而，在炎症中较常见的富含B细胞的三级淋巴结结构与更好的生存率相关。我们确定氧化还原中的代谢脆弱性（TP63，PSAT1和TFRC）。
更新日期：2019-08-08
中文翻译：
鳞状细胞肺癌的蛋白质组学景观。
基因组和转录组改变如何影响肺癌的功能蛋白质组尚未完全了解。在这里，我们整合了108名鳞状细胞肺癌（SCC）患者队列中的DNA拷贝数，体细胞突变，RNA测序和表达蛋白质组学。我们确定了三种蛋白质组学亚型，其中两种（发炎，氧化还原）占87％的肿瘤。炎症亚型富含嗜中性粒细胞，B细胞和单核细胞，并表达更多的PD-1。氧化还原肿瘤富含氧化还原和谷胱甘肽途径，并在3q2位点具有更多NFE2L2 / KEAP1改变和复制增益。蛋白质组亚型与患者生存率无关。然而，在炎症中较常见的富含B细胞的三级淋巴结结构与更好的生存率相关。我们确定氧化还原中的代谢脆弱性（TP63，PSAT1和TFRC）。
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