A novel chromatin regulator-related immune checkpoint related gene prognostic signature and potential candidate drugs for endometrial cancer patients.

IF 2.7 3区生物学

Hereditas Pub Date : 2022-10-18 DOI:10.1186/s41065-022-00253-w

Zesi Liu, Hongxia Yang, Ziyu Chen, Chunli Jing

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引用次数: 1

Abstract

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries and its prevalence is increasing. As an emerging therapy with a promising efficacy, immunotherapy has been extensively applied in the treatment of solid tumors. In addition, chromatin regulators (CRs), as essential upstream regulators of epigenetics, play a significant role in tumorigenesis and cancer development.

Methods: CRs and immune checkpoint-related genes (ICRGs) were obtained from the previous top research. The Genome Cancer Atlas (TCGA) was utilized to acquire the mRNA expression and clinical information of patients with EC. Correlation analysis was utilized for screen CRs-related ICRGs (CRRICRGs). By Cox regression and least absolute shrinkage and selection operator (LASSO) analysis, prognosis related CRRICRGs were screened out and risk model was constructed. The Kaplan-Meier curve was used to estimate the prognosis between high- and low-risk group. By comparing the IC50 value, the drugs sensitivity difference was explored. We obtained small molecule drugs for the treatment of UCEC patients based on CAMP dataset.

Results: We successfully constructed a 9 CRRICRs-based prognostic signature for patients with UCEC and found the riskscore was an independent prognostic factor. The results of functional analysis suggested that CRRICRGs may be involved in immune processes associated with cancer. Immune characteristics analysis provided further evidence that the CRRICRGs-based model was correlated with immune cells infiltration and immune checkpoint. Eight small molecule drugs that may be effective for the treatment of UCEC patients were screened. Effective drugs identified by drug sensitivity profiling in high- and low-risk groups.

Conclusion: In summary, our study provided novel insights into the function of CRRICRGs in UCEC. We also developed a reliable prognostic panel for the survival of patients with UCEC.

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一种新的染色质调控因子相关免疫检查点相关基因预后标记和子宫内膜癌患者的潜在候选药物。

背景:子宫内膜癌是发达国家最常见的妇科恶性肿瘤，其发病率呈上升趋势。免疫治疗作为一种新兴的治疗方法，在实体肿瘤的治疗中得到了广泛的应用。此外，染色质调节因子(CRs)作为表观遗传学上游的重要调节因子，在肿瘤发生和癌症发展中起着重要作用。方法:从以往的顶级研究中获得CRs和免疫检查点相关基因(ICRGs)。利用肿瘤基因组图谱(TCGA)获取EC患者的mRNA表达和临床信息。采用相关性分析筛选crs相关ICRGs (CRRICRGs)。通过Cox回归和最小绝对收缩和选择算子(LASSO)分析，筛选出与预后相关的CRRICRGs，构建风险模型。采用Kaplan-Meier曲线估计高、低危组预后。通过比较IC50值，探讨药物敏感性差异。我们基于CAMP数据集获得治疗UCEC患者的小分子药物。结果:我们成功构建了基于9 crricrs的UCEC患者预后特征，并发现风险评分是一个独立的预后因素。功能分析结果提示，CRRICRGs可能参与与癌症相关的免疫过程。免疫特性分析进一步证明基于crricrgs的模型与免疫细胞浸润和免疫检查点相关。筛选了8种可能有效治疗UCEC患者的小分子药物。通过药物敏感性分析在高危和低危人群中确定有效药物。结论:总之，我们的研究为CRRICRGs在UCEC中的功能提供了新的见解。我们还为UCEC患者的生存开发了一个可靠的预后小组。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.