Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma

作者：Yang Zhang, Fangqiu Fu, Qiao Zhang, Lingling Li, Hui Liu, Chaoqiang Deng, Qianqian Xue, Yue Zhao, Wenrui Sun, Han Han, Zhendong Gao, Chunmei Guo, Qiang Zheng, Hong Hu, Yihua Sun, Yuan Li, Chen Ding, Haiquan Chen · 发表于：Cell Reports Medicine · 年份：2024 · DOI：10.1016/j.xcrm.2023.101358 · 被引用次数：24 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cancer Genomics and Diagnostics

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.