Deciphering comprehensive features of tumor microenvironment controlled by chromatin regulators to predict prognosis and guide therapies in uterine corpus endometrial carcinoma

揭示染色质调节因子控制的肿瘤微环境的综合特征,以预测子宫体子宫内膜癌的预后并指导治疗

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作者:Qihui Wu, Ruotong Tian, Jiaxin Liu, Chunlin Ou, Yimin Li, Xiaodan Fu

Background

Dysregulation of chromatin regulators (CRs) can perturb the tumor immune microenvironment, but the underlying mechanism remains unclear. We focused on uterine corpus endometrial carcinoma (UCEC) and used gene expression data from TCGA-UCEC to investigate this mechanism.

Conclusion

A comprehensive assessment of CRRS could identify immune activation and improve the efficacy of UCEC treatments.

Methods

We used weighted gene co-expression network analysis (WGCNA) and consensus clustering algorithm to classify UCEC patients into Cluster_L and Cluster_H. TME-associated CRs were identified using WGCNA and differential gene expression analysis. A CR risk score (CRRS) was constructed using univariate Cox and LASSO-Cox regression analyses. A nomogram was developed based on CRRS and clinicopathologic factors to predict patients' prognosis.

Results

Lower CRRS was associated with lower grade, more benign molecular subtypes, and improved survival. Patients with low CRRS showed abundant immune infiltration, a higher mutation burden, fewer CNVs, and better response to immunotherapy. Moreover, low CRRS patients were more sensitive to 24 chemotherapeutic agents.

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