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基于二硫键相关 lncRNA 特征的黑色素瘤新型分子亚分型和精准治疗的阐明。

Clarifying new molecular subtyping and precise treatment of melanoma based on disulfidptosis-related lncRNA signature.

机构信息

Department of Blood Transfusion, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, China.

Zhongshan City People's Hospital, Zhongshan, 528400, Guangdong, China.

出版信息

Eur J Med Res. 2024 Sep 28;29(1):468. doi: 10.1186/s40001-024-02035-8.

DOI:10.1186/s40001-024-02035-8
PMID:39342368
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11438283/
Abstract

Disulfidptosis, the newest form of programmed cell death, is closely associated with the immune microenvironment of cancer cells. Long non-coding RNA (lncRNA) has also been found to play a crucial role in melanoma. However, the role of disulfidptosis-related lncRNA in melanoma remains unclear. Through bioinformatic analysis of the transcriptional, clinical, and pathological data from the TCGA-SKCM (The Cancer Genome Atlas-Skin cutaneous melanoma) database, we established a 2-Disulfidptosis-related lncRNA (DRL) prognostic model and a novel molecular subtype for melanoma. The survival and ROC curves of the 2-DRL prognostic model demonstrated its strong efficacy in predicting the prognosis of melanoma. The high-risk group of melanoma exhibited a significant decrease in ESTIMATEScore, ImmuneScore, and StromalScore, indicative of pronounced immune suppression and exhaustion. Subgroup C2 of melanoma displayed an immune-activated state, while subgroups C1 and C3 showed immune suppression and exhaustion, potentially leading to poorer prognosis. Subgroup C1 demonstrated better sensitivity to Zoledronate, UMI-77, Nilotinib, and Cytarabine. Subgroup C2 exhibited greater sensitivity to Ribociclib, XAV939, Topotecan, and Ruxolitinib. Subgroup C3 showed higher sensitivity to VX-11e, Ulixertinib, Trametinib, and Afatinib. This study revealed the immune microenvironment status and targeted drug sensitivity in melanoma patients with different risk scores and molecular subtypes, offering valuable guidance for clinical treatment and identifying significant DRL targets for future in-depth research.

摘要

二硫键程序性细胞死亡,是最新的形式程序化细胞死亡,与肿瘤细胞的免疫微环境密切相关。长链非编码 RNA(lncRNA)也被发现于黑色素瘤中发挥关键作用。然而,二硫键程序性细胞死亡相关 lncRNA 在黑色素瘤中的作用仍不清楚。通过对 TCGA-SKCM(癌症基因组图谱-皮肤黑色素瘤)数据库中的转录组、临床和病理数据进行生物信息学分析,我们建立了一个二硫键程序性细胞死亡相关 lncRNA(DRL)预后模型和黑色素瘤的新分子亚型。二硫键程序性细胞死亡相关 lncRNA 预后模型的生存和 ROC 曲线表明其在预测黑色素瘤预后方面具有很强的效果。黑色素瘤的高风险组表现出 ESTIMATEScore、ImmuneScore 和 StromalScore 的显著降低,表明存在明显的免疫抑制和衰竭。黑色素瘤亚组 C2 表现出免疫激活状态,而亚组 C1 和 C3 表现出免疫抑制和衰竭,可能导致预后较差。亚组 C1 对唑来膦酸、UMI-77、尼洛替尼和阿糖胞苷的敏感性更好。亚组 C2 对瑞博西利、XAV939、拓扑替康和鲁索利替尼的敏感性更高。亚组 C3 对 VX-11e、Ulixertinib、曲美替尼和阿法替尼的敏感性更高。本研究揭示了不同风险评分和分子亚型黑色素瘤患者的免疫微环境状态和靶向药物敏感性,为临床治疗提供了有价值的指导,并为未来深入研究确定了重要的 DRL 靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce7/11438283/c3fad298573b/40001_2024_2035_Fig8_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce7/11438283/1f1ef9d26200/40001_2024_2035_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce7/11438283/898c74606996/40001_2024_2035_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce7/11438283/8b3a30956095/40001_2024_2035_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ce7/11438283/c3fad298573b/40001_2024_2035_Fig8_HTML.jpg

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