Huang Chaobin, Peng Ying, Zheng Xueping, Cai Siqian, Lin Zhongmei, Zheng Yahan, Zheng Wei, Peng Fengying, Xu Yuanji
Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China.
Transl Cancer Res. 2025 Jul 30;14(7):4429-4446. doi: 10.21037/tcr-2025-1263. Epub 2025 Jul 27.
Anoikis resistance is a critical feature enabling cancer cells to survive during detachment from the extracellular matrix. This study aimed to identify and validate anoikis-related differentially expressed genes (ARDEGs) in nasopharyngeal carcinoma (NPC), providing new insights into the molecular mechanisms underlying NPC progression and potential therapeutic targets.
Four gene expression datasets from the Gene Expression Omnibus (GEO) database were integrated to form the GEO-Combined dataset. NPC and adjacent normal nasopharyngeal tissues comprising the Test_Data were subjected to RNA sequencing. The differentially expressed genes (DEGs) from the GEO-Combined and Test_Data datasets were screened. DEGs associated with anoikis were identified and termed as ARDEGs. The key genes were validated by quantitative real-time polymerase chain reaction (qRT-PCR).
A total of 104 ARDEGs were identified in our study. Five key genes (i.e., , , , , and ) were identified using the random forest (RF) and least absolute shrinkage and selection operator (LASSO) algorithms. A nomogram based on these five key genes showed robust diagnostic performance, with the area under the curve (AUC) underscoring its utility as a prognostic tool. Further, the functional enrichment analysis indicated that the risk model was associated with the biological pathways involved in tumor migration and invasion. Based on the model constructed from the five key genes, our study found 152 pairs of messenger RNA (mRNA)-transcription factor (TF) interaction relationships, which may provide insights into the mechanisms of metastasis and recurrence of NPC.
The identification and validation of ARDEGs in NPC highlighted critical molecular players in anoikis resistance, offering potential targets for therapeutic interventions. Our study provides a comprehensive understanding of the role of ARDEGs in NPC, paving the way for further research into targeted therapies for NPC.
失巢凋亡抗性是癌细胞在脱离细胞外基质后存活的关键特征。本研究旨在鉴定和验证鼻咽癌（NPC）中与失巢凋亡相关的差异表达基因（ARDEGs），为NPC进展的分子机制和潜在治疗靶点提供新见解。
整合来自基因表达综合数据库（GEO）的四个基因表达数据集，形成GEO合并数据集。对包含测试数据的NPC和相邻正常鼻咽组织进行RNA测序。筛选GEO合并数据集和测试数据集中的差异表达基因（DEGs）。鉴定与失巢凋亡相关的DEGs并将其称为ARDEGs。通过定量实时聚合酶链反应（qRT-PCR）验证关键基因。
本研究共鉴定出104个ARDEGs。使用随机森林（RF）和最小绝对收缩和选择算子（LASSO）算法鉴定出五个关键基因（即 、 、 、 和 ）。基于这五个关键基因的列线图显示出强大的诊断性能，曲线下面积（AUC）突出了其作为预后工具的效用。此外，功能富集分析表明，风险模型与肿瘤迁移和侵袭相关的生物学途径有关。基于由五个关键基因构建的模型，我们的研究发现了152对信使核糖核酸（mRNA）-转录因子（TF）相互作用关系，这可能为NPC转移和复发机制提供见解。
NPC中ARDEGs的鉴定和验证突出了失巢凋亡抗性中的关键分子参与者，为治疗干预提供了潜在靶点。我们的研究全面了解了ARDEGs在NPC中的作用，为进一步研究NPC的靶向治疗铺平了道路。
