Jin Haiyong, Zheng Lei, Wang Jie, Zheng Bo
Department of Otolaryngology, The Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Transl Cancer Res. 2024 Jul 31;13(7):3620-3636. doi: 10.21037/tcr-23-2360. Epub 2024 Jul 22.
In the context of head-and-neck squamous cell carcinoma (HNSCC), dendritic cells (DCs) assume pivotal responsibilities, acting as architects of antigen presentation and conductors of immune checkpoint modulation. In this study, we aimed to identify hub genes associated with DCs in HNSCC and explore their prognostic significance and implications for immunotherapy.
Integrated clinical datasets from The Cancer Genome Atlas (TCGA)-HNSCC and GSE65858 cohorts underwent meticulous analysis. Employing weighted gene co-expression network analysis (WGCNA), we delineated candidate genes pertinent to DCs. Through the application of random survival forest and least absolute shrinkage and selection operator (LASSO) Cox's regression, we derived key genes of significance. Lisa (epigenetic Landscape In Silico deletion Analysis and the second descendent of MARGE) highlighted transcription factors, with Dual-luciferase assays confirming their regulatory role. Furthermore, immunotherapeutic sensitivity was assessed utilizing the Tumor Immune Dysfunction and Exclusion online tool.
This study illuminated the functional intricacies of HNSCC DC subsets to tailor innovative therapeutic strategies. We leveraged clinical data from the TCGA-HNSCC and GSE65858 cohorts. We subjected the data to advanced analysis, including WGCNA, which revealed 222 DC-related candidate genes. Following this, a discerning approach utilizing random survival forest analysis and LASSO Cox's regression unveiled seven genes associated with the prognostic impact of DCs, notably and , associated with poor overall survival. Differential gene expression analysis between and DC cells revealed 208 differential expressed genes. Lisa analysis identified the top five significant transcription factors as , , , , and . The correlation between and was confirmed through quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Dual-luciferase assays in HEK293T cells. Additionally, and mutations were more common in high-risk DC subgroups. Importantly, the sensitivity to immunotherapy differed among the risk clusters. The low-risk cohorts were anticipated to exhibit favorable responses to immunotherapy, marked by heightened expressions of immune system-related markers. In contrast, the high-risk group displayed augmented proportions of immunosuppressive cells, suggesting a less conducive environment for immunotherapeutic interventions.
Our research may yield a robust DC-based prognostic system for HNSCC; this will aid personalized treatment and improve clinical outcomes as the battle against this challenging cancer continues.
在头颈部鳞状细胞癌（HNSCC）的背景下，树突状细胞（DCs）承担着关键职责，充当抗原呈递的架构师和免疫检查点调节的指挥者。在本研究中，我们旨在识别HNSCC中与DCs相关的枢纽基因，并探讨它们的预后意义以及对免疫治疗的影响。
对来自癌症基因组图谱（TCGA）-HNSCC和GSE65858队列的综合临床数据集进行了细致分析。采用加权基因共表达网络分析（WGCNA），我们描绘了与DCs相关的候选基因。通过应用随机生存森林和最小绝对收缩和选择算子（LASSO）Cox回归，我们得出了具有显著意义的关键基因。Lisa（表观遗传景观计算机删除分析和MARGE的第二代后裔）突出了转录因子，双荧光素酶测定证实了它们的调节作用。此外，利用肿瘤免疫功能障碍和排除在线工具评估免疫治疗敏感性。
本研究阐明了HNSCC DC亚群的功能复杂性，以制定创新的治疗策略。我们利用了来自TCGA-HNSCC和GSE65858队列的临床数据。我们对数据进行了高级分析，包括WGCNA，其揭示了222个与DC相关的候选基因。在此之后，一种利用随机生存森林分析和LASSO Cox回归的敏锐方法揭示了7个与DCs的预后影响相关的基因，特别是与总体生存率较差相关的 和 。 和 DC细胞之间的差异基因表达分析揭示了208个差异表达基因。Lisa分析确定了前五个显著的转录因子为 、 、 、 和 。通过定量逆转录聚合酶链反应（qRT-PCR）和HEK293T细胞中的双荧光素酶测定证实了 和 之间的相关性。此外， 和 突变在高风险DC亚组中更常见。重要的是，不同风险组对免疫治疗的敏感性不同。低风险队列预计对免疫治疗表现出良好反应，其特征是免疫系统相关标志物的表达增加。相比之下，高风险组显示免疫抑制细胞比例增加，这表明免疫治疗干预的环境不太有利。
我们的研究可能为HNSCC产生一个强大的基于DC的预后系统；随着与这种具有挑战性的癌症的斗争继续进行，这将有助于个性化治疗并改善临床结果。
