Descubrimiento de firmas proteogenómicas urinarias asociadas con el carcinoma de células escamosas de cabeza y cuello

Head and neck squamous cell carcinoma (HNSCC) is a major clinical challenge due to its aggressive nature and poor prognosis in advanced stages. Late detection, often due to delayed diagnosis, limits treatment success. With the aim of improving early diagnosis of HNSCC, we analyzed urine samples from 19 male HNSCC patients and 10 healthy male subjects, identifying 1427 proteins by mass spectrometry-based proteomics. Of these, 351 proteins were consistently detected in all subjects and selected for quantitative comparisons, which highlighted potential prognostic markers such as RNASE1, LRG1 and CD44. Proteogenomic cross-referencing of mass spectrometry-identified peptides with cancer variant databases suggested the presence of HNSCC-associated protein variants (e.g., GAA p.(Trp746Cys), SIAE p.(Pro210Leu)) as potential indicators of advanced disease. Functional analyzes linked the identified proteins to important tumor-related processes, including epithelial-mesenchymal transition and neutrophil degranulation. These results support urine as a valuable body fluid for proteogenomic profiling as it can be collected non-invasively, is available at large volumes, and enables longitudinal monitoring of molecular changes over time, providing a convenient window into systemic and tumor-associated processes. This study provides proof of concept that tumor related protein variants originating from HNSCC can be detected in urine, supporting its potential as a source of biomarkers for early detection. However, given the small, male-only cohort, these findings should be regarded as preliminary and will require validation in larger, sex-balanced cohorts, including patients with benign or inflammatory head and neck conditions, to confirm disease specificity. Altogether, our data underscores the translational promise of urinary proteogenomics in HNSCC management.