TCIRG1+neutrophils: biomarkers of adverse prognosis in tongue squamous cell carcinoma

Tongue squamous cell carcinoma (TSCC) is associated with an unfavorable prognosis, and the involvement of systemic inflammation and tumor-associated neutrophils (TANs) remains inadequately elucidated. This study was designed to assess the prognostic significance of inflammatory biomarkers and to delineate functionally distinct TAN subsets in TSCC. This retrospective investigation enrolled 851 patients with TSCC, stratified into discovery ( n = 596) and validation ( n = 255) cohorts. Pre-treatment hematological parameters were utilized to compute systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Neutrophil infiltration was quantitatively evaluated through hematoxylin and eosin (H&E) staining and multiplex immunohistochemistry (mIHC) in a representative subset of 120 cases. Proteomic profiling facilitated the identification of neutrophil-associated genes, whose prognostic relevance was subsequently corroborated through analysis of The Cancer Genome Atlas (TCGA) dataset and mIHC validation. Elevated NLR and MLR were associated with diminished overall and disease-free survival, with NLR demonstrating superior predictive capability. Increased intratumoral neutrophil density was significantly correlated with unfavorable clinical outcomes. Proteomic profiling identified T cell immunoregulatory protein 1 (TCIRG1) as a pivotal gene associated with neutrophil activity. mIHC analysis demonstrated that the density of TCIRG1 + TANs served as a more robust prognostic indicator of poor survival compared to the overall TANs density. NLR is robust prognostic biomarker in TSCC. The TCIRG1 + TAN subset emerges as a superior predictor of adverse outcomes, highlighting its potential as a therapeutic target.