Frontiers in Immunology (Mar 2023)

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

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

DOI
https://doi.org/10.3389/fimmu.2023.1139126
Journal volume & issue
Vol. 14

Abstract

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BackgroundDysregulation 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.MethodsWe 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.ResultsLower 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.ConclusionA comprehensive assessment of CRRS could identify immune activation and improve the efficacy of UCEC treatments.

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