Metabolic-inflammatory index CTI identifies high-risk early-stage natural killer/T-cell lymphoma and informs a novel prognostic model

The prognostic heterogeneity of early-stage natural killer/T-cell lymphoma (NKTCL) remains inadequately defined. This study aimed to investigate the prognostic value and potential biological relevance of the metabolic-inflammatory biomarkers in early-stage NKTCL. We conducted a secondary analysis on 166 patients with early-stage NKTCL from a multicenter clinical trial (NCT02631239). C-reactive protein-triglyceride-glucose Index (CTI) was calculated as: 0.412* Ln (CRP [mg/L]) + Ln (TG [mg/dL] × FPG [mg/dL])/2. Cox proportional hazards models and restricted cubic spline analyses were applied to assess the association and dose–response relationship between CTI and overall survival (OS). Mechanistic insights were explored through animal experiments and clinical lymphocyte-subset analyses. Independent prognostic factors were identified using multivariable Cox regression, and a composite prognostic model incorporating CTI, body mass index (BMI), and albumin (ALB) was subsequently developed and internally evaluated. High CTI was independently associated with inferior OS in patients with early-stage NKTCL, with a significant linear dose–response relationship. Patients with high CTI had a higher incidence of B symptoms and elevated lactate dehydrogenase and β2-microglobulin levels. A simplified CTI-BMI-ALB prognostic model demonstrated moderate predictive performance for 1-, 3-, and 5-year OS, with AUCs of 0.71, 0.71, and 0.69, respectively, and an overall C-index of 0.69 (95% CI: 0.59–0.79). In the present cohort, the CTI-BMI-ALB model showed improved discriminative performance compared with conventional prognostic indices and provided additional survival stratification among patients classified as low-risk or favorable-risk by these indices within this cohort. In vivo experiments showed that the Gubra-Amylin NASH diet-induced metabolic-inflammatory state with elevated CTI levels was associated with accelerated lymphoma progression, reduced intratumoral CD8 + T-cell infiltration, and increased proportions of Tregs and M2 macrophages. Consistently, clinical lymphocyte-subset analysis confirmed Treg enrichment in patients with high CTI and a positive association between CTI and the proportion of Tregs. CTI is an independent prognostic biomarker in early-stage NKTCL, reflecting systemic metabolic-inflammatory and immune dysregulation. The CTI-BMI-ALB model, which integrates inflammatory, nutritional, and metabolic dimensions, showed potential for complementary risk stratification beyond conventional prognostic indices and warrants further validation before broader clinical application.