Data Sheet 1_Integrative analysis of m7G methylation-associated genes prognostic signature with immunotherapy and identification of LARP1 as a key oncogene in head and neck squamous cell carcinoma.pdf

BackgroundN7-methylguanosine (m7G) methylation is an RNA modification associated with cancer progression, but its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear.
MethodsThis study analyzed the differential expression of m7G-related genes (m7GRGs) in HNSCC using the TCGA-HNSCC dataset, identifying key pathways associated with the cell cycle, DNA replication, and focal adhesion. A LASSO-Cox regression model was constructed based on four m7GRGs (EIF3D, EIF1, LARP1, and METTL1) and validated with GEO datasets and clinical samples. Further validation of gene upregulation in HNSCC tissues was conducted using RT-qPCR and immunohistochemistry, while the role of LARP1 in HNSCC cells was assessed via knockout experiments.
ResultsThe constructed model demonstrated strong predictive performance, with the risk score significantly correlating with prognosis, immune infiltration, and drug sensitivity. An external dataset and clinical specimens further confirmed the model’s predictive accuracy for immunotherapy response. Additionally, two regulatory axes—LINC00707/hsa-miR-30b-5p/LARP1 and SNHG16/hsa-miR-30b-5p/LARP1—were identified. LARP1 knockout experiments revealed that suppressing LARP1 markedly inhibited HNSCC cell proliferation, migration, and invasion.
ConclusionThe m7GRG-based prognostic model developed in this study holds strong clinical potential for predicting prognosis and therapeutic responses in HNSCC. The identification of LARP1 and its related regulatory pathways offers new avenues for targeted therapy in HNSCC.

背景：N7-甲基鸟苷（N7-methylguanosine，m7G）修饰是一种与癌症进展相关的RNA修饰，但其在头颈部鳞状细胞癌（head and neck squamous cell carcinoma，HNSCC）中的具体作用仍不明确。
方法：本研究利用TCGA-HNSCC数据集分析了HNSCC组织中m7G相关基因（m7G-related genes，m7GRGs）的差异表达情况，筛选出与细胞周期、DNA复制及黏着斑相关的关键通路。基于EIF3D、EIF1、LARP1与METTL1这4个m7GRGs构建了LASSO-Cox回归模型，并通过基因表达综合数据库（Gene Expression Omnibus，GEO）数据集及临床样本对模型进行验证。此外，本研究采用RT-qPCR与免疫组化技术验证了HNSCC组织中目标基因的上调表达，并通过基因敲除实验评估了LARP1在HNSCC细胞中的功能作用。
结果：所构建的模型展现出优异的预测性能，风险评分与患者预后、免疫浸润及药物敏感性显著相关。外部数据集与临床标本进一步证实了该模型对免疫治疗响应的预测准确性。此外，本研究还鉴定出两条调控轴：LINC00707/hsa-miR-30b-5p/LARP1及SNHG16/hsa-miR-30b-5p/LARP1。LARP1基因敲除实验结果显示，抑制LARP1的表达可显著抑制HNSCC细胞的增殖、迁移与侵袭能力。
结论：本研究构建的基于m7GRGs的预后模型在预测HNSCC患者预后及治疗响应方面具备良好的临床应用潜力。LARP1及其相关调控通路的鉴定为头颈部鳞状细胞癌的靶向治疗提供了全新的研究方向。