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miRNA 调控的预后标志物 LAYN 在泛癌中的免疫浸润和干性的综合全景。

Comprehensive landscape of the miRNA-regulated prognostic marker LAYN with immune infiltration and stemness in pan-cancer.

机构信息

Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

出版信息

J Cancer Res Clin Oncol. 2023 Oct;149(13):10989-11011. doi: 10.1007/s00432-023-04986-7. Epub 2023 Jun 19.

Abstract

BACKGROUND

COVID-19 has created a significant risk to worldwide public health. According to recent research, C-type lectins may be SARS-CoV-2 receptors. Layilin (LAYN), a broadly expressed integral membrane hyaluronan receptor with a C-type lectin structural domain, is a gene related to cell senescence. There are a few studies on C-type lectins in pan-cancer, and no pan-cancer analysis has been conducted for LAYN.

METHODS

The genotype tissue expression (GTEx) portal and the cancer genome map (TCGA) database were used to collect samples from healthy and cancer patients. Bioinformatics methods are used to construct immune landscape, mutation landscape, and stemness landscape of LAYN. The single-cell sequencing data were used from the CancerSEA website to analyze the functions of LAYN. The prognosis potential of LAYN was discussed based on machine learning.

RESULTS

LAYN is differentially expressed among cancers. Survival analysis indicated that LAYN was related to a poor overall survival (OS) rate in cancers, like HNSC, MESO, and OV. Mutational landscapes of LAYN in SKCM and STAD were constructed. LAYN was negatively related to Tumor Mutation Burden (TMB) in THCA, PRAD, and UCEC, and with the Microsatellite Instability (MSI) in STAD, LUAD, and UCEC. The immune landscape in pan-cancer suggested that LAYN may be involved in tumor immune escape. LAYN plays a crucial role in the infiltration of immune cells in malignant tumors. LAYN participates in methylation modifications and affects tumor proliferation and metastasis by regulating stemness. Analysis of single-cell sequencing data suggests that LAYN may participate in several biological processes, like stemness, apoptosis, and DNA repair. LAYN transcript was predicted as a liquid-liquid phase separation (LLPS)-related RNA. The results of KIRC were verified in the GEO and ArrayExpress databases. Furthermore, prognostic models based on machine learning of LAYN-related genes were established. Hsa-miR-153-5p and hsa-miR-505-3p may be the upstream miRNAs of LAYN and have a high value for tumor prognosis.

CONCLUSION

This study elucidated the functional mechanisms of LAYN from a pan-cancer perspective and provided novel insights into cancer prognosis, metastasis, and immunotherapy. LAYN has the potential to become a new target of mRNA vaccines and molecular therapies in tumors.

摘要

背景

COVID-19 对全球公共卫生造成了重大威胁。根据最近的研究,C 型凝集素可能是 SARS-CoV-2 的受体。Layilin(LAYN)是一种广泛表达的整联膜透明质酸受体,具有 C 型凝集素结构域,是与细胞衰老相关的基因。有一些关于泛癌中 C 型凝集素的研究,但没有针对 LAYN 的泛癌分析。

方法

使用基因型组织表达(GTEx)门户和癌症基因组图谱(TCGA)数据库收集来自健康和癌症患者的样本。使用生物信息学方法构建 LAYN 的免疫景观、突变景观和干性景观。使用 CancerSEA 网站的单细胞测序数据分析 LAYN 的功能。基于机器学习探讨 LAYN 的预后潜力。

结果

LAYN 在癌症中存在差异表达。生存分析表明,LAYN 与 HNSC、MESO 和 OV 等癌症的总生存期(OS)不良率相关。构建了 SKCM 和 STAD 中 LAYN 的突变景观。在 THCA、PRAD 和 UCEC 中,LAYN 与肿瘤突变负担(TMB)呈负相关,在 STAD、LUAD 和 UCEC 中与微卫星不稳定性(MSI)相关。泛癌的免疫景观表明,LAYN 可能参与肿瘤免疫逃逸。LAYN 在恶性肿瘤中免疫细胞浸润中起关键作用。LAYN 通过调节干性参与甲基化修饰,并影响肿瘤增殖和转移。单细胞测序数据的分析表明,LAYN 可能参与了几个生物学过程,如干性、细胞凋亡和 DNA 修复。预测 LAYN 转录本为液-液相分离(LLPS)相关 RNA。在 GEO 和 ArrayExpress 数据库中验证了 KIRC 的结果。此外,还建立了基于 LAYN 相关基因的机器学习预后模型。Hsa-miR-153-5p 和 hsa-miR-505-3p 可能是 LAYN 的上游 miRNA,对肿瘤预后具有较高价值。

结论

本研究从泛癌角度阐明了 LAYN 的功能机制,为癌症预后、转移和免疫治疗提供了新的见解。LAYN 有可能成为肿瘤 mRNA 疫苗和分子治疗的新靶点。

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