Zhang Nenghua, Qiu Xinyi, Chen Xingying, Du Cheng, Dong Jingyi, Li Xiaohong, Chen Bing, Zhang Lin, Zhang Yuyan
Clinical Laboratory, Jiaxing Hospital of Traditional Chinese Medicine, Zhejiang Chinese Medical University, Jiaxing, 314033, China.
The First School of Clinical Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310053, China.
Discov Oncol. 2025 Feb 28;16(1):253. doi: 10.1007/s12672-025-01971-z.
Aging and long non-coding RNAs (lncRNAs) are research hotspots in melanoma. However, no study has so far explored the relationship between melanoma prognosis and aging-related lncRNAs (ARLs).
The Cancer Genome Atlas database, the GTEx database, and the HAGR database were used in this study in a combined manner. Univariate and multivariate cox regression analyses were used to screen out lncRNA signatures associated with overall survival (OS) in the primary dataset. The risk scoring model was analyzed by risk stratification and tested internally. The protein expression levels of possible target genes of ARLs were verified by immunohistochemistry analysis in HPA database. Finally, gene enrichment analysis was performed.
In the primary dataset, five OS-related lncRNA signatures (AC011481.1, USP30-AS1, EBLN3P, LINC01527, HLA-DQB1-AS1) were screened out. The survival curve showed that the high-risk group had a worse prognosis than the low-risk group. The immunohistochemical analysis revealed that reduced expression of Epidermal Growth Factor Receptor (EGFR), along with increased expression of Activating Transcription Factor 2 (ATF2) and DNA Polymerase Delta 1 (POLD1), was linked to a worse prognosis. Finally, enrichment analysis revealed that OS-related DELs were significantly enriched in the regulation of reactive oxygen metabolism, etc. The ARGs were significantly activated in the SKCM tissues. The regulation of aging in melanoma cells may be realized through ferroptosis, immunity, and autophagy and so on.
The ARL signature obtained in this study had better prognostic ability than individual clinical features.
衰老和长链非编码RNA(lncRNA)是黑色素瘤研究的热点。然而,迄今为止尚无研究探讨黑色素瘤预后与衰老相关lncRNA(ARL)之间的关系。
本研究联合使用了癌症基因组图谱数据库、GTEx数据库和HAGR数据库。采用单因素和多因素cox回归分析在原始数据集中筛选出与总生存期(OS)相关的lncRNA特征。通过风险分层分析风险评分模型并进行内部验证。在HPA数据库中通过免疫组织化学分析验证ARL可能的靶基因的蛋白表达水平。最后进行基因富集分析。
在原始数据集中,筛选出5个与OS相关的lncRNA特征(AC011481.1、USP30-AS1、EBLN3P、LINC01527、HLA-DQB1-AS1)。生存曲线显示,高危组的预后比低危组差。免疫组织化学分析显示,表皮生长因子受体(EGFR)表达降低,同时激活转录因子2(ATF2)和DNA聚合酶δ1(POLD1)表达增加与预后较差有关。最后,富集分析显示,与OS相关的差异表达基因在活性氧代谢调控等方面显著富集。ARGs在皮肤黑色素瘤(SKCM)组织中显著激活。黑色素瘤细胞中的衰老调节可能通过铁死亡、免疫和自噬等实现。
本研究获得的ARL特征比个体临床特征具有更好的预后预测能力。