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oai:figshare.com:article/34046880 2026-10-01T16:05:33Z category_1 category_4 category_7 category_12 category_13 category_14 category_15 category_16 category_21 category_873 category_734 category_811 category_64 portal_63 item_type_6 month_year_10_2026

Integrated Multi-Omics Profiling of Thymoma Identifies Subtype-Specific Remodeling and Myasthenia Gravis-Associated Targets Yaohui Sun (400875) Jianfeng Mao (1672816) Xueqian Sun (6654341) Wanwei Cao (25157385) Jian Liu (33711) Guihong Zhang (316743) Xin Xu (11989) Ronghao Wang (11511413) Wenwen Huo (12958348) Jiebin Zuo (19125200) Biophysics Biochemistry Medicine Cell Biology Genetics Molecular Biology Neuroscience Physiology Biotechnology Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Mathematical Sciences not elsewhere classified Cancer link remain unclear free quantitative proteomics cancer genome atlas 4 ), acp5 profiled paired thymoma associated targets thymoma support membrane remodeling lipidomic signature characterized fatty acid pathways mg ), yet external transcriptomic validation thymoma identifies subtype lipid metabolic shifts tcga thymoma cohort specific remodeling reproducible metabolic candidate signature amino acid translational research thymomas exhibited prioritized candidates overall survival omics profiling myasthenia gravis mg status lipid subclasses linked hubs internal evaluation integrated multi independent association highlighting hmgcs1 future mechanistic derived 13 coordinated alterations clinicopathologic data based multi Thymoma is a rare thymic epithelial tumor strongly associated with myasthenia gravis (MG), yet the tumor intrinsic molecular states underlying this link remain unclear. Here, we profiled paired thymoma and distant nontumorous thymic tissues using untargeted metabolomics, lipidomics, and label-free quantitative proteomics, integrating these layers with MG status, clinicopathologic data, immunohistochemistry, and external transcriptomic validation from The Cancer Genome Atlas (TCGA) cohort. Thymomas exhibited a reproducible metabolic and lipidomic signature characterized by coordinated alterations in amino acid and nucleotide metabolism alongside structured changes in lipid subclasses that support membrane remodeling. Proteomic profiling distinguished tumors from distant nontumorous thymic tissue and identified three exploratory proteomic groups with distinct pathway patterns tightly coupled to lipid metabolic shifts. Integrated analyses identified HMGCS1 and SCP2 as subtype-enriched, lipid-linked hubs and uncovered an MG-associated molecular module comprising creatine, MePC(37:4), ACP5, AP1S1, NECTIN4, and fatty acid pathways. AP1S1 showed an independent association with the overall survival in the TCGA thymoma cohort. A derived 13-lipid panel showed high discrimination in an internal evaluation, supporting its potential as a candidate signature for further validation. This tissue-based multi-omics study systematically maps coordinated molecular remodeling in thymoma, highlighting HMGCS1, SCP2, and AP1S1 as prioritized candidates for future mechanistic and translational research. 2026-10-01T00:00:00Z Text Journal contribution 10.1021/acs.jproteome.6c00430.s001 https://figshare.com/articles/journal_contribution/Integrated_Multi-Omics_Profiling_of_Thymoma_Identifies_Subtype-Specific_Remodeling_and_Myasthenia_Gravis-Associated_Targets/34046880 CC BY-NC 4.0