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基于 XGBoost 识别赖氨酸乳酰化(kla)相关 lncRNA 特征,预测乳腺癌患者的预后和免疫微环境。

Identification of lysine lactylation (kla)-related lncRNA signatures using XGBoost to predict prognosis and immune microenvironment in breast cancer patients.

机构信息

School of Clinical Medicine, Fujian Medical University, No. 1 Xuefu North Road, University New District, Fuzhou, 350122, Fujian, China.

Department of Breast Surgery, Affiliated Hospital of Putian University, Putian, 351100, Fujian Province, China.

出版信息

Sci Rep. 2024 Sep 3;14(1):20432. doi: 10.1038/s41598-024-71482-4.

Abstract

Breast cancer (BC) stands as a predominant global malignancy, significantly contributing to female mortality. Recently uncovered, histone lysine lactylation (kla) has assumed a crucial role in cancer progression. However, the correlation with lncRNAs remains ambiguous. Scrutinizing lncRNAs associated with Kla not only improves clinical breast cancer management but also establishes a groundwork for antitumor drug development. We procured breast tissue samples, encompassing both normal and cancerous specimens, from The Cancer Genome Atlas (TCGA) database. Utilizing Cox regression and XGBoost methods, we developed a prognostic model using identified kla-related lncRNAs. The model's predictive efficacy underwent validation across training, testing, and the overall cohort. Functional analysis concerning kla-related lncRNAs ensued. We identified and screened 8 kla-related lncRNAs to formulate the risk model. Pathway analysis disclosed the connection between immune-related pathways and the risk model of kla-related lncRNAs. Significantly, the risk scores exhibited a correlation with both immune cell infiltration and immune function, indicating a clear association. Noteworthy is the observation that patients with elevated risk scores demonstrated an increased tumor mutation burden (TMB) and decreased tumor immune dysfunction and exclusion (TIDE) scores, suggesting heightened responses to immune checkpoint blockade. Our study uncovers a potential link between Kla-related lncRNAs and BC, providing innovative therapeutic guidelines for BC management.

摘要

乳腺癌(BC)是一种主要的全球恶性肿瘤,对女性死亡率有重大影响。最近发现,组蛋白赖氨酸酰化(kla)在癌症进展中起着关键作用。然而,其与 lncRNAs 的相关性尚不清楚。研究与 Kla 相关的 lncRNAs 不仅可以改善临床乳腺癌的管理,还可以为抗肿瘤药物的开发奠定基础。我们从癌症基因组图谱(TCGA)数据库中获取了乳腺组织样本,包括正常和癌症样本。利用 Cox 回归和 XGBoost 方法,我们使用鉴定出的 kla 相关 lncRNAs 开发了一个预后模型。该模型的预测效果在训练、测试和整个队列中进行了验证。接着进行了 kla 相关 lncRNAs 的功能分析。我们鉴定并筛选了 8 个 kla 相关 lncRNAs 来构建风险模型。通路分析揭示了免疫相关通路与 kla 相关 lncRNAs 风险模型之间的联系。重要的是,风险评分与免疫细胞浸润和免疫功能呈正相关,表明存在明确的关联。值得注意的是,观察到风险评分升高的患者具有更高的肿瘤突变负担(TMB)和更低的肿瘤免疫功能障碍和排除(TIDE)评分,提示对免疫检查点阻断有更高的反应。我们的研究揭示了 kla 相关 lncRNAs 与 BC 之间的潜在联系,为 BC 的管理提供了新的治疗指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8acd/11371909/67ec25086399/41598_2024_71482_Fig1_HTML.jpg

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