Shuaib Mohd, Saini Diksha, Sharma Gargi, Singh Ishwar, Gupta Sanjay, Kumar Shashank, Kumar Pramod
Molecular Signaling & Drug Discovery Laboratory, Department of Biochemistry, Central University of Punjab, Guddha, Bathinda 151401, India.
Department of Molecular Biology, ICMR-National Institute of Cancer Prevention and Research, Noida 201301, India.
Cancers (Basel). 2025 Jun 27;17(13):2169. doi: 10.3390/cancers17132169.
: 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. : 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. : 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. : Taken together, these findings suggest that targeting these miRNAs could modulate immune evasion mechanisms and potentially enhance the efficacy of ICB therapies in HNC.
头颈癌（HNC）仍然是一项全球性的健康挑战，复发或晚期疾病患者的5年生存率较低。免疫检查点阻断疗法已成为一种有望改善治疗结果的方法；然而，由于免疫逃逸机制，其有效性有限，有效率仅为15-20%。微小RNA（miRNA）失调在促进这种免疫逃逸中起关键作用。在本研究中，我们旨在鉴定其表达改变导致HNC免疫逃逸的特定miRNA。
我们采用了一种综合生物信息学方法，包括差异表达分析、生存分析、靶标预测、KEGG免疫途径分析、蛋白质-蛋白质相互作用网络以及使用计算机工具鉴定枢纽基因。
我们的分析表明，miR-18a和miR-2355的高表达与生存率降低相关，在晚期患者中，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的低表达与预后不良相关，在疾病进展过程中，生存率分别从40.1个月降至19.2个月和从50.1个月降至26.8个月。进一步的途径分析表明，这些miRNA显著参与关键免疫逃逸信号通路的调节，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为潜在的失调miRNA靶标，在免疫相关信号通路中富集。
综上所述，这些发现表明，靶向这些miRNA可以调节免疫逃逸机制，并有可能提高ICB疗法在HNC中的疗效。
