Overexpression of KMT9α is associated with poor outcome in cholangiocarcinoma patients.

Purpose: The newly discovered histone methyltransferase KMT9 serves as an epigenetic regulator of carcinogenesis in various cancer entities. For the first time, we investigated the presence of KMT9α in cholangiocarcinoma, the association with histologic subtypes, and its impact on survival.

Methods: A tissue microarray cohort of all CCA patients who underwent surgical resection with curative intent between 08/2005 and 12/2021 at the University Hospital Frankfurt was immunohistochemically analyzed with the KMT9α antibody. For overall survival, Kaplan-Meier curves and Cox-regression analyses were performed.

Results: In total, 174 patients were suitable for IHC analysis. Of the patients, 35.1% (n = 61) overexpressed KMT9α. Kaplan-Meier curves revealed a median OS of 34.75 months (95% CI = 20.23-49.27 months) for all CCA patients positive for KMT9α in comparison to 54.21 months (95% CI = 41.78-66.63 months) for patients lacking KMT9α overexpression (p = 0.004). Subtype analysis revealed strong differences in KMT9α expression. Multivariate Cox regression analysis identified KMT9α as an independent risk factor for shorter OS in CCA.

Conclusion: This study demonstrates that a marked subset of CCA patients exhibit overexpression of KMT9α. These findings underscore the prognostic significance of KMT9α and reinforce its potential as a therapeutic target, consistent with its role in other cancer types.