DataSheet2_Ferroptosis-related gene ATG5 is a novel prognostic biomarker in nasopharyngeal carcinoma and head and neck squamous cell carcinoma.ZIP

Nasopharyngeal carcinoma (NPC), a subtype of head and neck squamous cell carcinoma (HNSCC), is a malignant tumor that originates in the mucosal epithelium of the nasopharynx. Ferroptosis plays a key role in tumor suppression, while its prognostic value and critical factors in NPC have not been further explored. We select the Cancer Genome Atlas (TCGA) HNSCC dataset and the Gene Expression Omnibus (GEO) dataset of NPC samples, and find that ferroptosis-related factor ATG5 shows a high expression level with poor overall survival (OS) in HNSCC and NPC samples and is positively correlated with PD-L1/PD-L2 expression (p < 0.05). Furthermore, ATG5 high expression HNSCC patients show poor efficacy and short survival after receiving immune checkpoint blockade therapy treatment (p < 0.05). Moreover, ATG5 is significantly positively correlated with G2M checkpoint pathway (ρSpearman = 0.41, p < 0.01), and G2M checkpoint inhibitor drugs have lower IC50 in HNSCC patients with high expression of ATG5 (p < 0.01), indicating the potential value of G2M inhibitors in HNSCC/NPC treatment. In summary, our study shows that ferroptosis-related factors play a key role in immune infiltration in NPC and HNSCC, and ATG5, as a key immune invasion-related ferroptosis-related factor, has the potential to be a novel prognostic biomarker and a potential target in therapy for NPC and HNSCC.

鼻咽癌（Nasopharyngeal carcinoma, NPC）是头颈部鳞状细胞癌（head and neck squamous cell carcinoma, HNSCC）的一个亚型，是一种起源于鼻咽黏膜上皮的恶性肿瘤。铁死亡（Ferroptosis）在肿瘤抑制中发挥关键作用，但其在NPC中的预后价值及关键调控因子尚未得到深入探究。本研究选取了癌症基因组图谱（Cancer Genome Atlas, TCGA）的头颈部鳞状细胞癌数据集以及基因表达综合数据库（Gene Expression Omnibus, GEO）的鼻咽癌样本数据集，研究发现铁死亡相关因子ATG5在头颈部鳞状细胞癌和鼻咽癌样本中呈高表达，且与较差的总生存期（overall survival, OS）相关，同时其表达与程序性死亡受体配体1/2（PD-L1/PD-L2）的表达呈正相关（p < 0.05）。进一步分析显示，ATG5高表达的头颈部鳞状细胞癌患者在接受免疫检查点阻断治疗后疗效更差、生存期更短（p < 0.05）。此外，ATG5的表达与G2/M检查点通路呈显著正相关（斯皮尔曼相关系数ρ=0.41，p < 0.01），且在ATG5高表达的头颈部鳞状细胞癌患者中，G2/M检查点抑制剂的半数抑制浓度（IC50）更低（p < 0.01），这表明G2/M抑制剂在头颈部鳞状细胞癌/鼻咽癌治疗中具有潜在应用价值。综上，本研究表明铁死亡相关因子在鼻咽癌和头颈部鳞状细胞癌的免疫浸润中发挥关键作用，而ATG5作为一种与免疫侵袭相关的关键铁死亡调控因子，有望成为鼻咽癌和头颈部鳞状细胞癌新型预后生物标志物及潜在治疗靶点。