MYC upregulation as candidate predictive biomarker for radioresistance in cervical cancer

BACKGROUND: A subset of uterine cervical cancers recurs locally after definitive radiotherapy, highlighting the need for establishing biomarkers to predict radioresistance for dose optimisation. However, low local recurrence rate constitutes a barrier to research progress. This study aimed at exploring candidate predictive biomarker of radioresistance of uterine cervical cancer by analyzing multiple omics layers using nested case-control approach. METHODS: A discovery cohort (n = 8) was created from a series of 192 patients (all with squamous cell carcinoma of the uterine cervix underwent definitive radiotherapy) by 1:1 random case-control matching on pelvic recurrence (PR) for RNA sequencing. A validation cohort (n = 54) was created from the same series by 1:2 propensity score matching on PR for panel-based DNA sequencing and pelvic recurrence-free survival (PRFS) analysis. by using the Kaplan-Meier method and cause-specific proportional hazards models. RESULTS: In the discovery cohort, Gene set enrichment analysis revealed that the genes targeted by MYC were upregulated in patients with PR. In the validation cohort, the prevalence of MYC amplification was significantly greater in patients with PR than in those without (72% vs. 36%, respectively). The 5-year PRFS of patients with MYC amplification was significantly worse than that of those without (47.4% vs. 80.6%, respectively). Multivariate analysis identified MYC amplification as the significant predictor of PR. CONCLUSIONS: These data suggest that upregulation of MYC plays a role in radioresistance of uterine cervical cancer, making MYC amplification a potential predictive biomarker for radioresistance.