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Source Data from Comprehensive Proteogenomic Profiling Reveals the Molecular Characteristics of Colorectal Cancer at Distinct Stages of Progression

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posted on 2024-09-04, 07:21 authored by Lingling Li, Dongxian Jiang, Hui Liu, Chunmei Guo, Qiao Zhang, Xuedong Li, Xiaojian Chen, Zheqi Chen, Jinwen Feng, Subei Tan, Wen Huang, Jie Huang, Chen Xu, Chen-Ying Liu, Wei Yu, Yingyong Hou, Chen Ding

Source data of the revised manuscript.

Funding

National Key Research and Development Program of China (NKPs)

National Natural Science Foundation of China (NSFC)

Program of Shanghai Academic Research Leader (Shanghai Academic Research Leader)

Major Projects of Special Development Funds in Zhangjiang National Independent Innovation Demonstration Zone, Shanghai

China Postdoctoral Science Foundation (China Postdoctoral Foundation Project)

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ARTICLE ABSTRACT

Colorectal cancer is the second most common malignant tumor worldwide. Analysis of the changes that occur during colorectal cancer progression could provide insights into the molecular mechanisms driving colorectal cancer development and identify improved treatment strategies. In this study, we performed an integrated multiomic analysis of 435 trace tumor samples from 148 patients with colorectal cancer, covering nontumor, intraepithelial neoplasia (IEN), infiltration, and advanced stage colorectal cancer phases. Proteogenomic analyses demonstrated that KRAS and BRAF mutations were mutually exclusive and elevated oxidative phosphorylation in the IEN phase. Chr17q loss and chr20q gain were also mutually exclusive, which occurred predominantly in the IEN and infiltration phases, respectively, and impacted the cell cycle. Mutations in TP53 were frequent in the advanced stage colorectal cancer phase and associated with the tumor microenvironment, including increased extracellular matrix rigidity and stromal infiltration. Analysis of the profiles of colorectal cancer based on consensus molecular subtype and colorectal cancer intrinsic subtype classifications revealed the progression paths of each subtype and indicated that microsatellite instability was associated with specific subtype classifications. Additional comparison of molecular characteristics of colorectal cancer based on location showed that ANKRD22 amplification by chr10q23.31 gain enhanced glycolysis in the right-sided colorectal cancer. The AOM/DSS-induced colorectal cancer carcinogenesis mouse model indicated that DDX5 deletion due to chr17q loss promoted colorectal cancer development, consistent with the findings from the patient samples. Collectively, this study provides an informative resource for understanding the driving events of different stages of colorectal cancer and identifying the potential therapeutic targets.Significance: Characterization of the proteogenomic landscape of colorectal cancer during progression provides a multiomic map detailing the alterations in each stage of carcinogenesis and suggesting potential diagnostic and therapeutic approaches for patients.

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