Investigating the Role of ALPK2 in Endometrial Cancer Progression: From Biological Function to Clinical Translation

Given the limitations of traditional indicators in evaluating the prognosis of endometrial cancer, this study identified the core genes related to prognosis, diagnosis, and treatment within the alpha-protein kinase (ALPK) family to address the lack of research on ALPK family genes in endometrial cancer. Using data from the TCGA database, we combined bioinformatics analyses (Cox regression, Kaplan-Meier analysis, GSVA enrichment, KEGG pathway analysis) and cell experiments (constructing ALPK2 knockdown/overexpression models; conducting clone formation assays; CCK-8 and other experiments), analysis of the associations among gene expression, prognosis, clinicopathological characteristics, and drug sensitivity was conducted. Only ALPK2 was identified as an independent risk factor for poor prognosis of endometrial cancer (HR > 1, P < 0.05). It was highly expressed in tumor tissues (P < 0.01) and associated with high-risk characteristics such as serous subtype and stage III/IV (P < 0.001). ALPK2 promoted tumor progression by regulating core processes such as proliferation and invasion, and pathways including ECM-receptor interaction and PI3K-Akt signaling. Its high expression was associated with resistance to cisplatin and paclitaxel, as well as sensitivity to olaparib (P < 0.01). Moreover, it demonstrated good diagnostic efficacy for stage III with an AUC of 0.872 and showed broad applicability. ALPK2 is a potential key molecule for prognostic assessment, diagnostic accuracy, and targeted therapy of endometrial cancer, providing a new basis for optimizing the diagnosis and treatment of this disease.