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通过 LDL 代谢解码皮肤黑色素瘤预后:基于 101 种机器学习算法的单细胞转录组学分析。

Deciphering cutaneous melanoma prognosis through LDL metabolism: Single-cell transcriptomics analysis via 101 machine learning algorithms.

机构信息

Department of Plastic Surgery, Xiangya Hospital, Central South University, Changsha, China.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

出版信息

Exp Dermatol. 2024 Apr;33(4):e15070. doi: 10.1111/exd.15070.

DOI:10.1111/exd.15070
PMID:38570935
Abstract

Cutaneous melanoma poses a formidable challenge within the field of oncology, marked by its aggressive nature and capacity for metastasis. Despite extensive research uncovering numerous genetic and molecular contributors to cutaneous melanoma development, there remains a critical knowledge gap concerning the role of lipids, notably low-density lipoprotein (LDL), in this lethal skin cancer. This article endeavours to bridge this knowledge gap by delving into the intricate interplay between LDL metabolism and cutaneous melanoma, shedding light on how lipids influence tumour progression, immune responses and potential therapeutic avenues. Genes associated with LDL metabolism were extracted from the GSEA database. We acquired and analysed single-cell sequencing data (GSE215120) and bulk-RNA sequencing data, including the TCGA data set, GSE19234, GSE22153 and GSE65904. Our analysis unveiled the heterogeneity of LDL across various cell types at the single-cell sequencing level. Additionally, we constructed an LDL-related signature (LRS) using machine learning algorithms, incorporating differentially expressed genes and highly correlated genes. The LRS serves as a valuable tool for assessing the prognosis, immunity and mutation status of patients with cutaneous melanoma. Furthermore, we conducted experiments on A375 and WM-115 cells to validate the function of PPP2R1A, a pivotal gene within the LRS. Our comprehensive approach, combining advanced bioinformatics analyses with an extensive review of current literature, presents compelling evidence regarding the significance of LDL within the cutaneous melanoma microenvironment.

摘要

皮肤黑色素瘤在肿瘤学领域构成了严峻的挑战,其特点是侵袭性强且易于转移。尽管大量研究揭示了许多导致皮肤黑色素瘤发展的遗传和分子因素,但关于脂质(尤其是低密度脂蛋白 LDL)在这种致命皮肤癌中的作用,仍存在关键的知识空白。本文通过深入探讨 LDL 代谢与皮肤黑色素瘤之间的复杂相互作用,努力填补这一知识空白,阐明脂质如何影响肿瘤进展、免疫反应以及潜在的治疗途径。从 GSEA 数据库中提取与 LDL 代谢相关的基因。我们获取并分析了单细胞测序数据(GSE215120)和批量 RNA 测序数据,包括 TCGA 数据集、GSE19234、GSE22153 和 GSE65904。我们的分析揭示了 LDL 在单细胞测序水平上在各种细胞类型中的异质性。此外,我们使用机器学习算法构建了一个 LDL 相关特征(LRS),其中包含差异表达基因和高度相关基因。LRS 可作为评估皮肤黑色素瘤患者预后、免疫和突变状态的有用工具。此外,我们还在 A375 和 WM-115 细胞上进行了实验,以验证 LRS 中的关键基因 PPP2R1A 的功能。我们的综合方法结合了先进的生物信息学分析和对现有文献的广泛回顾,为 LDL 在皮肤黑色素瘤微环境中的重要性提供了令人信服的证据。

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