Zhang Miao, Song Shaoran, Wang Bo, Shang Yangyang, Liu Peijun, Li Juan
Center for Translational Medicine, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Key Laboratory for Tumor Precision Medicine of Shaanxi Province, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Transl Cancer Res. 2025 Feb 28;14(2):949-965. doi: 10.21037/tcr-24-1532. Epub 2025 Feb 26.
The prognostic value of necroptosis-related microRNAs (miRNAs), which are important in tumorigenesis and development, remains unclear. Therefore, we aimed to screen prognostic necroptosis-related miRNAs in esophageal cancer (EC).
Nine necroptosis-related miRNA expression profiles and associated clinical data of EC patients were obtained from The Cancer Genome Atlas (TCGA) database. The relationships between necroptosis-related miRNAs and overall survival (OS) were determined via Cox regression model analysis. Target genes of the miRNAs were investigated in TargetScan, miRDB, and miRTarBase. The biological functions of these genes were evaluated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. For the most significant correlation between miR-425-5p expression and the survival of EC patients, the effect of miR-425-5p on necroptosis was explored in EC cells. The relationship between targeted gene expression and immune infiltration was also analyzed and validated.
Hsa-miR-425-5p, hsa-miR-500a-3p, hsa-miR-7-5p and hsa-miR-200a-5p were selected for the construction of a prognostic signature based on their correlation with the survival of EC patients. EC patients were divided into high- and low-risk groups according to the median value of the risk score. Patients in the high-risk group tended to have higher death rates than those in the low-risk group (P<0.05). The risk score was an independent prognostic indicator for the OS of EC patients [hazard ratio (HR) >1, P<0.05]. The prognostic model had good predictive efficiency. The genes targeted by necroptosis-related miRNAs were significantly enriched in apoptosis etc. The inhibition of miR-425-5p promoted necroptosis in EC cells by targeting branched chain amino acid transaminase 1 (). The expression level of was significantly correlated with immune infiltration.
A necroptosis-related four-miRNA model was constructed successfully to predict the potential value of the four miRNAs in the prognosis of EC, which can be conducive to promoting the therapeutic effect on EC.
坏死性凋亡相关的微小RNA（miRNA）在肿瘤发生和发展中起重要作用，但其预后价值仍不清楚。因此，我们旨在筛选食管癌（EC）中与坏死性凋亡相关的预后miRNA。
从癌症基因组图谱（TCGA）数据库中获取9个与坏死性凋亡相关的miRNA表达谱以及EC患者的相关临床数据。通过Cox回归模型分析确定坏死性凋亡相关miRNA与总生存期（OS）之间的关系。在TargetScan、miRDB和miRTarBase中研究miRNA的靶基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析评估这些基因的生物学功能。对于miR-425-5p表达与EC患者生存之间最显著的相关性，在EC细胞中探讨了miR-425-5p对坏死性凋亡的影响。还分析并验证了靶基因表达与免疫浸润之间的关系。
基于hsa-miR-425-5p、hsa-miR-500a-3p、hsa-miR-7-5p和hsa-miR-200a-5p与EC患者生存的相关性，选择它们构建预后特征。根据风险评分的中位数将EC患者分为高风险组和低风险组。高风险组患者的死亡率往往高于低风险组（P<0.05）。风险评分是EC患者OS的独立预后指标[危险比（HR）>1，P<0.05]。预后模型具有良好的预测效率。坏死性凋亡相关miRNA靶向的基因在凋亡等方面显著富集。抑制miR-425-5p通过靶向支链氨基酸转氨酶1促进EC细胞中的坏死性凋亡。其表达水平与免疫浸润显著相关。
成功构建了一种与坏死性凋亡相关的四miRNA模型，以预测这四种miRNA在EC预后中的潜在价值，这有助于提高对EC的治疗效果。
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