KDM4A as a prognostic marker of oral squamous cell carcinoma: Evidence from tissue microarray studies in a multicenter cohort

PURPOSE: Previous studies have identified histone demethylase KDM4A to be a key epigenetic priming factor for the invasive squamous cell carcinoma growth and metastasis. The purpose of this study was to examine KDM4A as an independent prognostic marker in oral squamous cell carcinoma, using multicenter tissue microarrays. RESULTS: The expression of KDM4A was significantly correlated with lymph node metastasis and TNM stage. KDM4A overexpression was associated with poor overall survival, and it was found to be a statistically significant independent predictor of all-cause mortality. These findings are validated by external TCGA HNSCC data. Addition of KDM4A expression improved the discriminatory accuracy of standard clinicopathologic features for prediction of cancer-specific survival (Model 4, area under the curve = 0.740, 95% confidence interval = 0.685 to 0.795, and Model 3, AUC = 0.695, 95% CI = 0.637 to 0.753, respectively). MATERIALS AND METHODS: KDM4A expression was measured by immunohistochemistry, using tissue microarrays of OSCC samples collected from 313 patients. Kruskal-Wallis and chi-square tests were applied to investigate the correlation between KDM4A expression and clinicopathological factors. Overall survival analysis was performed using the Kaplan-Meier and multivariable logistic regression models, and the predictive ability of KDM4A in combination with known OSCC risk factors was evaluated. Receiver operating characteristic curves were used to assess discriminatory accuracy of these models. Additionally, disease-free survival was analyzed in patients with head and neck SCC reported on The Cancer Genome Atlas database. CONCLUSIONS: KDM4A expression is an independent predictor for the survival time of patients with OSCC and may be a valuable consideration to postoperative treatment options.