近日，美国博德研究所Michael A. Gillette等研究人员合作绘制出肺鳞状细胞癌的蛋白质组学图谱。相关论文于2021年8月5日发表于国际学术期刊《细胞》。

研究人员报道了肺鳞状细胞癌（LSCC）的蛋白质基因组图谱，对LSCC的生物学进行了更深入的阐述，并具有潜在的治疗意义。研究人员发现NSD3是FGFR1扩增肿瘤和低p63肿瘤中过表达治疗靶标survivin的替代驱动因素。SOX2被认为是不可药物靶向的，但研究人员的分析为探索染色质修饰因子（如LSD1和EZH2）来靶向SOX2过表达肿瘤提供了可能。这些数据表明，翻译后修饰（包括泛素化）之间的串扰会对代谢途径进行复杂的调节。

许多与免疫有关的蛋白质基因组观察表明了进一步研究的方向。对CDKN2A突变的蛋白质基因组学分析表明，在宣布CDK4/6抑制不成功之前，需要对RB1蛋白的表达和磷酸化进行更细致的评估。最后，LSCC、LUAD和HNSCC之间的三角关系确定了独特和共同的治疗弱点。这些观察和蛋白质基因组学数据资源可能指导LSCC的生物学和治疗研究。

据悉，LSCC仍然是癌症死亡的主要原因，但治疗方案很少。

附：英文原文

Title: A proteogenomic portrait of lung squamous cell carcinoma

Author: Shankha Satpathy, Karsten Krug, Pierre M. Jean Beltran, Sara R. Savage, Francesca Petralia, Chandan Kumar-Sinha, Yongchao Dou, Boris Reva, M. Harry Kane, Shayan C. Avanessian, Suhas V. Vasaikar, Azra Krek, Jonathan T. Lei, Eric J. Jaehnig, Tatiana Omelchenko, Yifat Geffen, Erik J. Bergstrom, Vasileios Stathias, Karen E. Christianson, David I. Heiman, Marcin P. Cieslik, Song Cao, Xiaoyu Song, Jiayi Ji, Wenke Liu, Kai Li, Bo Wen, Yize Li, Zeynep H. Gümü, Myvizhi Esai Selvan, Rama Soundararajan, Tanvi H. Visal, Maria G. Raso, Edwin Roger Parra, zgün Babur, Pankaj Vats, Shankara Anand, Tobias Schraink, MacIntosh Cornwell, Fernanda Martins Rodrigues, Houxiang Zhu, Chia-Kuei Mo, Yuping Zhang, Felipe da Veiga Leprevost, Chen Huang, Arul M. Chinnaiyan, Matthew A. Wyczalkowski, Gilbert S. Omenn, Chelsea J. Newton, Stephan Schurer, Kelly V. Ruggles, David Feny, Scott D. Jewell, Mathangi Thiagarajan, Mehdi Mesri, Henry Rodriguez, Sendurai A. Mani, Namrata D. Udeshi, Gad Getz, James Suh, Qing Kay Li, Galen Hostetter, Paul K. Paik, Saravana M. Dhanasekaran, Ramaswamy Govindan, Li Ding, Ana I. Robles, Karl R. Clauser, Alexey I. Nesvizhskii, Pei Wang, Steven A. Carr, Bing Zhang, D.R. Mani

Issue&Volume: 2021/08/05

Abstract: Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

DOI: 10.1016/j.cell.2021.07.016

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00857-6