Background: Head and neck cancer (HNC) remains a global health challenge with a poor 5-year survival rate among patients with relapsed or advanced-stage disease. Immune checkpoint blockade therapies have emerged as a promising approach to improve outcomes; however, their effectiveness is limited, with response rates of only 15–20% because of immune evasion mechanisms. MicroRNA (miRNA) dysregulation plays a key role in facilitating such immune evasion. In this study, we aim to identify specific miRNAs whose altered expression contributes to immune escape in HNC.Methods: We employed an integrated bioinformatics approach, incorporating differential expression analysis, survival analysis, target prediction, KEGG immune pathway analysis, a protein–protein interaction network, and the identification of hub genes using in silico tools.Results: Our analysis revealed that a high expression of miR-18a and miR-2355 was associated with reduced survival, with the median survival decreasing from 42.9 to 27.8 months, respectively, in advanced-stage patients. Conversely, a low expression of let-7c and miR-6510 was linked to poor prognosis, with survival decreasing from 40.1 to 19.2 months and from 50.1 to 26.8 months, respectively, across disease progression. Further pathway analysis revealed that these miRNAs are significantly involved in the regulation of key immune evasion signaling pathways, including T cell receptor, PD-L1/PD-1 checkpoint, JAK-STAT, TGF-beta, NF-kappa B, and TNF signaling pathways. Hub gene analysis identified AKT1, STAT3, NFKB1, CD4, IL2RB, TLR4, and CTLA-4 as potential dysregulated miRNA targets, with enrichment in immune-related signaling pathways.Conclusions: Taken together, these findings suggest that targeting these miRNAs could modulate immune evasion mechanisms and potentially enhance the efficacy of ICB therapies in HNC.
背景：头颈癌（HNC）仍是全球性的健康挑战，复发或晚期患者的5年生存率较低。免疫检查点阻断疗法已成为改善预后的有效策略，但由于免疫逃逸机制的存在，其疗效有限，应答率仅为15-20%。微小RNA（miRNA）的失调在促进此类免疫逃逸中起关键作用。本研究旨在鉴定在HNC中表达改变并促进免疫逃逸的特异性miRNA。 方法：我们采用整合生物信息学方法，包括差异表达分析、生存分析、靶基因预测、KEGG免疫通路分析、蛋白质-蛋白质相互作用网络构建，并利用计算工具识别枢纽基因。 结果：分析显示，miR-18a和miR-2355的高表达与生存期缩短相关，晚期患者中位生存期分别从42.9个月降至27.8个月。相反，let-7c和miR-6510的低表达与不良预后相关，在疾病进展过程中生存期分别从40.1个月降至19.2个月、从50.1个月降至26.8个月。进一步通路分析表明，这些miRNA显著参与调控关键免疫逃逸信号通路，包括T细胞受体、PD-L1/PD-1检查点、JAK-STAT、TGF-β、NF-κB和TNF信号通路。枢纽基因分析确定AKT1、STAT3、NFKB1、CD4、IL2RB、TLR4和CTLA-4为潜在失调的miRNA靶点，这些基因在免疫相关信号通路中富集。 结论：综上所述，这些发现表明靶向这些miRNA可能调节免疫逃逸机制，并有望增强HNC中免疫检查点阻断疗法的疗效。
Dysregulated miRNA Expression and Its Association with Immune Checkpoints in Head and Neck Cancer
肿瘤(癌症)患者之家