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Wu, Yige

Publications and source records attributed to Wu, Yige.

6 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Proteogenomic insights suggest druggable pathways in endometrial carcinoma

We characterized a prospective endometrial carcinoma (EC) cohort containing 138 tumors and 20 enriched normal tissues using 10 different omics platforms. Targeted quantitation of two peptides can predict antigen processing and presentation machinery activity, and may inform patient selection for immunotherapy. Association analysis between MYC activity and metformin treatment in both patients and cell lines suggests a potential role for metformin treatment in non-diabetic patients with elevated MYC activity. PIK3R1 in-frame indels are associated with elevated AKT phosphorylation and increased sensitivity to AKT inhibitors. CTNNB1 hotspot mutations are concentrated near phosphorylation sites mediating pS45-induced degradation of β-catenin, which may render Wnt-FZD antagonists ineffective. Deep learning accurately predicts EC subtypes and mutations from histopathology images, which may be useful for rapid diagnosis. Overall, this study identified molecular and imaging markers that can be further investigated to guide patient stratification for more precise treatment of EC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Histopathologic and proteogenomic heterogeneity reveals features of clear cell renal cell carcinoma aggressiveness

Clear cell renal cell carcinomas (ccRCCs) represent ∼75% of RCC cases and account for most RCC-associated deaths. Inter- and intratumoral heterogeneity (ITH) results in varying prognosis and treatment outcomes. To obtain the most comprehensive profile of ccRCC, we perform integrative histopathologic, proteogenomic, and metabolomic analyses on 305 ccRCC tumor segments and 166 paired adjacent normal tissues from 213 cases. Combining histologic and molecular profiles reveals ITH in 90% of ccRCCs, with 50% demonstrating immune signature heterogeneity. High tumor grade, along with BAP1 mutation, genome instability, increased hypermethylation, and a specific protein glycosylation signature define a high-risk disease subset, where UCHL1 expression displays prognostic value. Single-nuclei RNA sequencing of the adverse sarcomatoid and rhabdoid phenotypes uncover gene signatures and potential insights into tumor evolution. In vitro cell line studies confirm the potential of inhibiting identified phosphoproteome targets. This study molecularly stratifies aggressive histopathologic subtypes that may inform more effective treatment strategies.

CPTAC↗
DOE OSTI2020

SupplementalFilesCPTAC_ProteogenomicOvarianPaper_2020_02_27

Interactive plots (in HTML/javascript) as supplemental files for the paper titled: Proteogenomic Characterization of Ovarian High-Grade Serous Cancer Implicates Mitotic Kinases, Replication Stress in Observed Chromosomal Instability. The plots represent the differential expression of proteins (File 1) and phosphopeptides (File 2) comparing tumor to normal tissue.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2020

Proteogenomic Characterization of Endometrial Carcinoma

We undertook a comprehensive proteogenomic characterization of 95 endometrial carcinomas, of which 83 were endometrioid tumors and 12 were serous tumors. This analysis revealed new consequences of perturbations to the p53 and Wnt/ß-catenin pathways, identified a potential role for circRNAs in the epithelial-mesenchymal transition, and provided new insights into proteomic markers of clinical and genomic tumor subgroups, some of which are in known druggable pathways. We performed a broad genome-wide acetylation survey, one of the first of its kind, yielding insights into regulatory mechanisms of histone acetylation. We also characterized the tumor immune landscape, including immunogenic alterations, neoantigens, common cancer/testis antigens, and the immune microenvironment, all of which can inform immunotherapy decisions. Collectively, our multi-omic analyses provide a valuable resource for researchers and clinicians, further our understanding of the molecular mechanisms underlying endometrial carcinoma, and identify new avenues for investigating potential therapeutic targets.

59 BASIC BIOLOGICAL SCIENCES↗