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基于生物信息学分析构建肥胖子宫内膜癌患者免疫相关基因预后模型

Construction of an immune-related gene prognostic model for obese endometrial cancer patients based on bioinformatics analysis.

作者信息

Tong Yun, Zhu Tao, Xu Fei, Yang Wenjun, Wang Yakun, Zhang Xianze, Chen Xiujie, Liu Lei

机构信息

Department of Pharmacogenomics, College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Department of Pharmacy, Beidahuang Industry Group General Hospital, Harbin, 150088, China.

出版信息

Heliyon. 2024 Jul 30;10(15):e35488. doi: 10.1016/j.heliyon.2024.e35488. eCollection 2024 Aug 15.

Abstract

BACKGROUND

The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported.

METHODS

This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients' responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram.

RESULTS

The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability.

CONCLUSION

Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

摘要

背景

肿瘤微环境(TME)影响肿瘤预后。然而,其对肥胖型子宫内膜癌(EC)患者结局的影响尚未见报道。

方法

本研究对503例EC患者的转录组谱和医学数据进行回顾性分析。通过评估算法计算免疫评分。利用Cox和LASSO回归分析确定与预后相关的关键基因,并创建风险预后评分(RPS)以预测肥胖型EC患者的结局。使用拷贝数变异(CNV)和体细胞突变信息研究基因突变与RPS之间的关系。采用单样本基因集富集分析(ssGSEA)和基因集变异分析(GSVA)检测与关键基因相关的免疫浸润和免疫通路富集情况。分别利用肿瘤免疫功能障碍和排除(TIDE)算法和基因表达谱数据库(GDSC)预测患者对免疫治疗和化疗的反应。最后,我们使用“rms”R软件包构建列线图。

结果

肥胖型EC患者的预后与免疫评分相关。鉴定出三个关键基因(EYA4、MBOAT2和SCGB2A1)。通过使用预后基因进行风险分层和预后预测,建立了肥胖型EC患者的风险预后评分(RPS)。RPS越高,预后越差,基因组改变越恶性。与低RPS组相比,高RPS组大多数免疫细胞的比例显著降低。高RPS组与G2M、MYC和E2F相关通路如细胞增殖、细胞周期和细胞死亡有关。顺铂、他莫昔芬和拓扑替康对低RPS组的疗效更佳。值得注意的是,列线图具有良好的预测能力。

结论

我们的研究为肥胖型EC患者设计了一种可靠的RPS,以预测其预后、免疫侵袭性以及对免疫治疗和药物治疗的反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ea2/11336703/0e7030648d95/gr1.jpg

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