Fig. 7

The clinical relevance of the OTUD4/GSDME axis and radiotherapy response in NPC. A Representative immunohistochemical images of OTUD4 low- and high- expression in NPC tissues (left and right, respectively). The magnified inset area is shown at the bottom. Scale bars represent 50 μm. B The IHC score of OTUD4 in the radiosensitive and radioresistant tissues. C The association between OTUD4 expression and radiotherapy response, χ2 test. RS, radiosensitive; RR, radioresistant. D 5-year PFS for NPC was calculated by Kaplan–Meier analysis, compared using the Log Rank test, and stratified by low and high OTUD4 levels. Progression-free survival, PFS. E Representative NPC cases received radiotherapy alone, showing the relationship between OTUD4 expression, GSDME expression, serum LDH, and cancer regression. The yellow dashed lines indicate tumor in nasopharyngoscopy images. Scale bars represent 50 μm. RT, radiotherapy. F The correlation between OTUD4 expression and GSDME expression. G The correlation between OTUD4/GSDME expression and radiosensitivity. H Comparison of the progression-free survival and locoregional recurrence-free survival between 39 OTUD4^low/GSDME^low, 56 OTUD4^high/GSDME.^high and 55 others. Actuarial probabilities were analyzed by Kaplan–Meier (Log Rank test). (I) Proposed model showing that GSDME-dependent pyroptosis is identified as a critical determinant of radiosensitivity in NPC. In addition, OTUD4/GSDME interaction inhibits OTUD4-mediated GSDME ubiquitination and stability, thereby promoting GSDME-dependent pyroptosis and enhancing radiosensitivity in NPC. *P < 0.05, **P < 0.01, ****P < 0.0001