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机器学习鉴定皮肤黑色素瘤中的乳酰化基因 CALML5 及其相关 lncRNAs。

Identification of lactylation gene CALML5 and its correlated lncRNAs in cutaneous melanoma by machine learning.

机构信息

Department of Stomatology, Linping Campus, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Department of Emergency Surgery, Linping Campus, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Medicine (Baltimore). 2023 Nov 24;102(47):e35999. doi: 10.1097/MD.0000000000035999.

Abstract

As a product of glycolysis, lactate contributes to cancer proliferation, immunosuppression, and metastasis via histone lactylation. However, the relationship between cutaneous melanoma (CM) and lactylation-associated genes and lncRNAs has remained unclear. In this study, 4 mechanism learning algorithms and integrated bioinformatic analyses were employed to identify the core lactylation-associated genes and lncRNAs. Subsequently, 2 risk signatures based on the hub lactylation-associated genes and lncRNAs were constructed for CM patients. As a result, CALML5 was identified as a core lactylation-associated gene in CM, and its expression was found to be associated with patients survival and immune infiltration, suggesting its relevance as a potential therapeutic target. Additionally, this study provided clarification on hub CALML5-associated lncRNAs in CM, offering insights into their roles in the disease. Meanwhile, 2 identified risk signatures were both strongly linked to the prognosis and cancer growth of CM, underscoring their potential as valuable prognostic indicators. Furthermore, mechanistic analyses suggested a significant association between the risk signature and the immune microenvironment in CM, highlighting potential immune-related implications in disease progression. In conclusion, we propose that lactylation-associated genes and lncRNAs hold promise as potential targets in CM. Moreover, our findings revealed a significant correlation between lactylation and the immune microenvironment, providing crucial insights for guiding individualized treatment strategies in CM.

摘要

作为糖酵解的产物,乳酸通过组蛋白乳酰化促进癌症增殖、免疫抑制和转移。然而,皮肤黑色素瘤(CM)与乳酰化相关基因和 lncRNA 之间的关系仍不清楚。在这项研究中,采用了 4 种机制学习算法和综合生物信息学分析来识别核心乳酰化相关基因和 lncRNA。随后,基于核心乳酰化相关基因和 lncRNA 构建了 2 个 CM 患者的风险签名。结果表明,CALML5 是 CM 中核心乳酰化相关基因,其表达与患者的生存和免疫浸润有关,表明其作为潜在治疗靶点的相关性。此外,本研究阐明了 CM 中核心 CALML5 相关 lncRNA 的作用,为其在疾病中的作用提供了深入了解。同时,鉴定的 2 个风险签名都与 CM 的预后和癌症生长密切相关,强调了它们作为有价值的预后指标的潜力。此外,机制分析表明,风险签名与 CM 中的免疫微环境之间存在显著关联,强调了在疾病进展中免疫相关的潜在影响。总之,我们提出乳酰化相关基因和 lncRNA 可能成为 CM 的潜在治疗靶点。此外,我们的研究结果揭示了乳酰化与免疫微环境之间的显著相关性,为指导 CM 的个体化治疗策略提供了重要的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2d/10681499/3c38ce2649a1/medi-102-e35999-g001.jpg

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