O-GlcNAcylation levels predict radiotherapy outcome in non-small cell lung cancer

Limited evidence exists on the role of protein glycosylation, particularly O-GlcNAcylation (O-GlcNAc), in predicting radiotherapy (RT) response in non-small cell lung cancer (NSCLC). This study aimed to investigate O-GlcNAc expression, glucose metabolism indicators, and their associations with RT response and prognosis in NSCLC.

We conducted a retrospective cohort study of 216 NSCLC patients who underwent RT and positron emission tomography-computed tomography (PET-CT) imaging. O-GlcNAc expression in pretreatment primary tumor specimens was evaluated by immunohistochemistry (IHC), and patients were categorized into high- and low-expression groups. All patients were matched for age, sex, diagnosis, and pathological stage. Clinical features were reviewed, and multivariable logistic regression was applied to analyze associations between O-GlcNAc levels and clinical parameters. The conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). Kaplan-Meier analysis was performed to evaluate the prognostic impact of O-GlcNAc expression. Pretreatment blood glucose levels and primary tumor glucose uptake [maximum standardized uptake value (SUVmax)] from PET-CT were also assessed, and correlation analyses were conducted to determine their relationships with RT response and survival outcomes.

Low O-GlcNAc expression was independently associated with poor RT response (P=0.005; OR =2.47; 95% CI: 1.32-4.64) and significantly predicted shorter progression-free survival (PFS; log-rank P=0.049) and overall survival (OS; log-rank P=0.008). In contrast, blood glucose levels (P=0.59) and primary tumor SUVmax (P=0.38) showed no association with RT response, and neither blood glucose nor SUVmax correlated with PFS; however, high SUVmax was predictive of shorter OS (log-rank P=0.03).

High O-GlcNAc expression was a predictor of favorable RT response and improved PFS and OS in NSCLC patients.