XXII. Nádory jícnu a žaludku

341. INTEGROVANÁ PROSTOROVÁ PROTEOMIKA A SEKVENOVÁNÍ DNA JÍCNOVÝCH NÁDORŮ A PŘILEHLÝCH ŽALUDEČNÍCH A JÍCNOVÝCH TKÁNÍ

HENEK T.¹, HRŮZOVÁ K.¹, MIHAL JURÍKOVÁ Z.¹, HERNYCHOVÁ L.¹, HUPP T.², O’NEILL J.³

¹ RECAMO, MOÚ Brno, ² Cancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, ³ Cambridge Oesophagogastric Centre, Cambridge University Hospitals NHS Foundation Trust

Esophageal tumors exhibit substantial molecular heterogeneity, complicating classification and therapeutic stratification. In this study, we performed spatial proteomic analysis of esophageal tumor tissue, adjacent gastric, and esophageal tissues from four patients (three tissue regions per patient) using liquid chromatography coupled to high-resolution mass spectrometry. Proteomic profiling against a canonical protein database revealed distinct tumor proteotypes consistent with recently described molecular tumor genotypes, corroborating published sequencing-based classifications at the protein level [1]. Integration with available DNA sequencing data from cut tumor tissues demonstrated concordance between selected genomic alterations and corresponding protein variants. However, many DNA mutations were instead detected as wild-type proteins. This discrepancy may have several possible explanations, including intratumor heterogeneity, spatial mismatch between the tissue regions subjected to sequencing and proteomic analysis, allelic expression bias or stromal contamination. Furthermore, a subset of DNA sequencing identified mutations appeared to be enriched in adjacent gastric tissue rather than in tumor tissue, suggesting distinct tissue origins for some genomic alterations. Unique protein identifications can reveal actively dysregulated biological pathways, enabling a more accurate functional classification of tumor subtypes than genomic data alone. This enables a more accurate and biologically relevant classification of tumor subtypes, particularly in heterogeneous cancers where genomic mutations may not necessarily translate into functional protein expression. Consequently, integrating proteomic data with genomic analyses can improve molecular stratification, refine subtype classification, and identify clinically relevant pathways that may serve as diagnostic markers or therapeutic targets.

Supported by the project SALVAGE (P JAC; reg. no. CZ.02.01.01/00/22_008/0004644) –⁠ funded by the European Union and by the State Budget of the Czech Republic and by MH CZ –⁠ DRO (MMCI, 00209805).

Literature: [1] Zamani SA, Wu L, Black EL et al. Integrated epidemiological and molecular data inform the relationship between precancer and cancer states of esophageal adenocarcinoma. Nat Med 2026; 32 : 1805–1816. doi: 10.1038/s41591-026-04331-8.