Abstract 6540: Multiscale protein networks: de novo aberrant protein interactions and oncogenic regulators in seven cancer types

We conducted integrative proteomic network analyses of 687 cases across 7 cancer types including breast cancer (115 tumor samples), clear cell renal carcinoma (100 tumor samples), colorectal cancer (91 tumor samples), hepatocellular carcinoma (101 tumor samples), lung adenocarcinoma (104 tumor samples), stomach adenocarcinoma (80 tumor samples), and uterine corpus endometrial carcinoma (96 tumor samples). Using Multi-scale embedded gene co-expression network analysis (MEGENA), we constructed co-expression protein network for each cancer type, and interrogated the network topology and co-expressed protein modules. For each cancer type, we identified disease-associated pathways as co-expressed protein modules enriched for differentially expressed proteins in tumor. Comparing with respective cancer transcriptome network models, this systematically revealed proteome-specific cancer subnetworks associated with heme metabolism, DNA repair, spliceosome, oxidative phosphorylation and KRAS oncogenic signaling pahways in several cancer types. Cross-cancer comparison identified highly preserved protein modules showing robust pan-cancer interactions and identified endoplasmic reticulum-associated degradation (ERAD) and N-acetyltransferase activity as the central functional axes. Then, we utilized these network models to predict pan-cancer protein network regulators in the up-stream of disease-associated pathways. The predicted pan-cancer regulators were experimentally validated by loss-of-function to confer anti-tumor effects in diverse cancer types: lung (H847), colon (HCT116), fetal kidney (HEK293T) and breast (MDA-MB-231) cancer cells. Overall, the study was designed to provide tractable network models of cancer proteome, and unlock the further potentials to understand oncogenic regulators and mechanisms in different cancer types. Citation Format: Won Min Song, Abdulkadir Elmas, Richard Farias, Peng Xu, Xianxiao Zhou, Benjamin Hopkins, Kuan-lin Huang, Bin Zhang. Multiscale protein networks: de novo aberrant protein interactions and oncogenic regulators in seven cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6540.