HYDIN mutation status as a potential predictor of immune checkpoint inhibitor efficacy in melanoma

Background: The advent of immune checkpoint inhibitors (ICIs) has altered the outlook for cancer treatment. The estimation of predictive biomarkers could contribute to maximizing the benefits from ICIs treatment. Here, we explored the association between HYDIN mutations (HYDIN-MUT) in melanoma and ICIs efficacy. Methods: Clinical data and sequencing data from published studies were utilized to assess the association between HYDIN-MUT and the efficacy of ICIs treatment in melanoma patients. Results: Compared to other tumor types, HYDIN (36.14%) has the highest mutation rate in melanoma patients. In the anti-PD-1 treated cohort (n = 254), the HYDIN-MUT patients had a longer OS after ICIs treatment than the HYDIN wild-type (HYDIN-WT) patients (HR = 0.590 [95% CI, 0.410-0.847], P = 0.004); the objective response rate (ORR) and durable clinical benefit (DCB) were increased in patients with HYDIN-MUT (ORR = 46.25, DCB = 56.00%) compared to patients with HYDIN-WT (ORR = 30.99%, DCB = 42.76%) (ORR: P = 0.019; DCB: P = 0.060). In the anti-CTLA4 treated cohort (n = 174), HYDIN-MUT patients achieved significantly longer OS than HYDIN-WT patients (HR = 0.549 [95% CI, 0.366-0.823], P = 0.003); the proportion of ORR and DCB in HYDIN-MUT patients was significantly higher than that in HYDIN-WT patients (ORR 40.54% vs. 14.42%, P = 0.031; DCB 45.76% vs. 22.22%, P = 0.002). Further gene set enrichment analysis demonstrated that DNA repair and anti-tumor immunity were significantly enhanced in HYDIN-MUT patients. Conclusions: HYDIN mutations are a potential predictive biomarker of ICIs efficacy in melanoma patients.