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Molecular characterization of breast cancer and multiple primary malignancies: the latest application using unmarked quantitative proteomics
Int J Surg. 2025 Jul 22. doi: 10.1097/JS9.0000000000002999. Online ahead of print.
ABSTRACT
BACKGROUND: Breast cancer remains the most prevalent malignancy among women, and patients presenting with both breast and lung cancer pose significant challenges in clinical diagnosis and treatment. Currently, comprehensive multi-omics analyses for such multiple malignancies are lacking.
METHODS: An integrated multi-omics analysis was performed, incorporating quantitative proteomics and radiomics data from patients with single primary breast cancer as well as those with multiple primary tumors (breast and lung cancer).
RESULTS: Quantitative proteomics analysis revealed four distinct molecular signatures (Types I-IV). Patients with single breast cancer exhibited driving pathways primarily linked to cell proliferation (e.g., HER2), whereas those with multiple breast cancers showed enrichment in ER-related and proliferative pathways. In contrast, patients with multiple lung cancers displayed pathways associated with immune response and immune escape. Additionally, immune subtyping identified three distinct immune landscapes (Types I-III). Radiomic analysis demonstrated strong correlations between these molecular/immune subtypes and imaging findings. Patients with high imaging information scores exhibited pronounced tumor heterogeneity and reduced immune infiltration.
CONCLUSIONS: This study provides new insights into the molecular pathogenesis of multiple primary malignancies, particularly breast and lung cancer.
PMID:40694032 | DOI:10.1097/JS9.0000000000002999
Integrated Multi-omics Data Analysis and In Vitro Validation Reveal the Crucial Role of Glycogen Metabolism in Gastric Cancer
J Cancer. 2025 Jan 13;16(4):1243-1263. doi: 10.7150/jca.104424. eCollection 2025.
ABSTRACT
Background: This study aimed to investigate glycogen metabolism in gastric cancer (GC) and develop a glycogen-based riskScore model for predicting GC prognosis. Methods: Patients' expression profiles for 33 tumor types were retrieved from TCGA. Four GC bulk and one single-cell sequencing datasets were obtained from GEO database. This study also enrolled a bladder urothelial carcinoma immunotherapeutic IMvigor210 cohort. The ssGSEA method was conducted to assess glycogen biosynthesis and degradation level. Consensus clustering analysis was conducted to identify different clusters. A glycogen riskScore signature was developed to evaluate prognostic value across different cohorts. Besides, in vitro experiments were conducted to further evaluate the role of glycogen metabolism related genes in GC. Results: Both glycogen biosynthesis and degradation were significantly associated with worse overall survival and were also related with malignant phenotype in GC at both bulk and single-cell levels. Differential outcomes and immune functions were verified in the three identified clusters. The constructed glycogen riskScore model accurately classified GC patients with different outcomes, genomic and immune landscape, and performed well in predicting prognosis through external validation, immunotherapy and pan-cancer cohorts. Furthermore, the riskScore could predict response to chemotherapy and immunotherapy. Functional analyses revealed the signature's connection to pro-tumor and immunosuppression related pathways across pan-cancer. Additionally, glycogen metabolism related genes were found to regulate the malignant phenotypes of GC cells. Conclusion: This study revealed important roles of glycogen metabolism in promoting progression of GC and presented a glycogen riskScore model as a novel tool for predicting prognosis and treatment response.
PMID:39895799 | PMC:PMC11786036 | DOI:10.7150/jca.104424
Tumor-selective activity of RAS-GTP inhibition in pancreatic cancer
Nature, Published online: 08 April 2024; doi:10.1038/s41586-024-07379-z
Tumor-selective activity of RAS-GTP inhibition in pancreatic cancer7-Dehydrocholesterol dictates ferroptosis sensitivity
Nature, Published online: 31 January 2024; doi:10.1038/s41586-023-06983-9
7-Dehydrocholesterol (7-DHC) is a natural anti-ferroptotic metabolite and pharmacological manipulation of 7-DHC levels shows promise as a therapeutic strategy for cancer and ischaemia–reperfusion injury.Cell death affecting the progression of gastric cancer
Cell Death Discovery, Published online: 29 August 2022; doi:10.1038/s41420-022-01161-8
Cell death affecting the progression of gastric cancer