与瞬时受体电位（TRP）通道相关的长链非编码RNA（lncRNA）AC092535.4和LINC01637，作为葡萄膜黑色素瘤的新型预后生物标志物。
TRP channel-related LncRNAs, AC092535.4 and LINC01637, as novel prognostic biomarkers for uveal melanoma.
作者信息
Zhang Min, Ni Jinglan, Liu Dongyue, Cui Yubo, Ma Xiaochen, Zhao Jun
机构信息
The Second Clinical Medical College, Jinan University, Shenzhen, Guangdong, China.
Department of Ophthalmology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University and The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
出版信息
Front Genet. 2024 Jul 23;15:1441732. doi: 10.3389/fgene.2024.1441732. eCollection 2024.
INTRODUCTION
Transient receptor potential (TRP) channels function as cellular sensors with a broad impact, and their dysregulation is linked to numerous cancers. The influence of TRP channel-related long noncoding RNAs (TCRLs) on uveal melanoma (UM) remains poorly understood.
METHODS
We employed bioinformatics to examine the RNA-seq data and relevant clinical information of UM in the TCGA databases. By implementing coexpression analysis, we identified differentially expressed TCRLs. Using univariate Cox regression analysis, selection operator (LASSO) algorithm and stepwise regression, five key prognostic biomarkers were chosen. The high- and low-risk groups were divided based on the risk scores. Afterwards, the prediction performance of the signature was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) survival analysis. The functional enrichment analysis of TCRLs was also investigated. Following that, we examined immune cell infiltration, immune checkpoint expression, and tumor immune microenvironment between patients in high and low risk groups. TCRLs were validated using Random forests and multifactor Cox analysis. Candidate biomarkers were identified and screened. Finally, the effects of the candidate biomarkers on the proliferation, migration and invasion of UM cells were detected by CCK-8 assay, migration assay and perforation invasion assay.
RESULTS
The risk score generated by five TCRLs demonstrated robust predictive power. The high-risk group exhibited a poorer prognosis, increased immune cell infiltration, and an active tumor immune microenvironment compared to the low-risk group. Furthermore, two TCRLs of risk score, AC092535.4 and LINC01637, were screened to multiplex modelling. The experiments demonstrated that UM cells were suppressed following AC092535.4 or LINC01637 knockdown.
DISCUSSION
Two TCRLs, AC092535.4 and LINC01637, serve as novel prognostic biomarkers for uveal melanoma and may present potential therapeutic targets.
引言
瞬时受体电位（TRP）通道作为具有广泛影响的细胞传感器，其功能失调与多种癌症相关。TRP通道相关长链非编码RNA（TCRL）对葡萄膜黑色素瘤（UM）的影响仍知之甚少。
方法
我们运用生物信息学方法分析了TCGA数据库中UM的RNA测序数据及相关临床信息。通过共表达分析，我们鉴定出差异表达的TCRL。利用单因素Cox回归分析、套索（LASSO）算法和逐步回归，筛选出五个关键的预后生物标志物。根据风险评分将患者分为高风险组和低风险组。随后，通过受试者工作特征（ROC）曲线和Kaplan-Meier（K-M）生存分析评估该标志物的预测性能。我们还对TCRL进行了功能富集分析。在此之后，我们检测了高风险组和低风险组患者之间的免疫细胞浸润、免疫检查点表达及肿瘤免疫微环境。使用随机森林和多因素Cox分析对TCRL进行验证。鉴定并筛选候选生物标志物。最后，通过CCK-8检测、迁移实验和穿孔侵袭实验检测候选生物标志物对UM细胞增殖、迁移和侵袭的影响。
结果
由五个TCRL生成的风险评分显示出强大的预测能力。与低风险组相比，高风险组预后较差，免疫细胞浸润增加，肿瘤免疫微环境活跃。此外，筛选出风险评分的两个TCRL，即AC092535.4和LINC01637进行多重建模。实验表明，敲低AC092535.4或LINC01637后UM细胞受到抑制。
讨论
两个TCRL，AC092535.4和LINC01637，作为葡萄膜黑色素瘤新的预后生物标志物，可能成为潜在的治疗靶点。
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