ArticleMedicine2025
A cancer-testis antigen signature for predicting prognosis and response to immunotherapy in acute myeloid leukemia.
Article in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Acute myeloid leukemia (AML) remains a challenging hematologic malignancy with poor survival rates, underscoring the need for precise prognostic biomarkers and therapeutic strategies. Cancer-testis antigens (CTAs), with tumor-restricted expression and immunogenicity, have not been systematically explored for prognosis prediction in AML. Here, we developed a novel CTA-based prognostic signature to predict survival and immunotherapy response in AML patients. Utilizing RNA-seq and clinical data from the TCGA-Acute Myeloid Leukemia cohort (n = 126, training set) and the GSE71014 dataset (n = 104, validation set), we identified 21 prognosis-associated CTAs via univariate Cox regression. Least absolute shrinkage and selection operator and multivariate Cox regression refined the model to 5 key genes: ACRBP, IGF2BP3, SPAG1, TEX101, and KDM5B. The CTA score, calculated from gene expression and regression coefficients, stratified patients into high- and low-risk groups with distinct overall survival (P < .001). The model exhibited robust predictive accuracy, with time-dependent area under the curve values of 0.863 (TCGA-Acute Myeloid Leukemia training set) and 0.723 (GSE71014 validation cohort) for 5-year overall survival. High CTA scores correlated with adverse prognosis, elevated monocytes and M0 macrophages infiltration, and enhanced immunotherapy responsiveness. Functional enrichment analysis revealed dysregulation in several key AML-related pathways, including leukocyte migration, PI3K-Akt signaling, and cytokine pathways. A nomogram integrating CTA score and age further improved prognostic precision (concordance index = 0.77). Drug sensitivity profiling highlighted differential therapeutic vulnerabilities between risk groups. This study established and validated a novel CTA-based prognostic tool for prognostic stratification and personalized treatment guidance in AML, bridging molecular insights with clinical applications.
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