Zhang Xinyi, Lin Yiqi, Shi Liang, Zhai Aixia, Wu Chao, Zhu Qian-Ying
Department of Laboratory Medicine, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Department of Endocrinology, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
Front Oncol. 2025 Jan 24;15:1451034. doi: 10.3389/fonc.2025.1451034. eCollection 2025.
Nasopharyngeal carcinoma (NPC), one of the most common malignancies of the head and neck, is characterised by a complex pathogenesis and an unfavourable prognosis. Recently, disulfidoptosis, a novel form of cell death, has been proposed. Several studies in recent years have extensively investigated the function of the disulfidoptosis-related SLC7A11 gene in cancer, but the role of its partner protein, SLC3A2, remains unknown unclear in NPC.
GEO database analysis confirmed SLC3A2's prognostic impact on nasopharyngeal carcinoma. ROC, Kaplan-Meier analyses, and stage-specific expression studies showed a strong correlation with poor HNSC prognosis. GO and KEGG analyses pinpointed relevant signaling pathways. In vitro, SLC3A2's influence on cell proliferation, migration, and invasion was evaluated through CCK8, wound healing, colony formation, transwell assays, and cell cycle analysis.
In this study, we identified the high expression of SLC3A2 in NPC and head and neck squamous cell carcinoma (HNSC) and analyzed its potential mechanism and correlation with patient prognosis. Furthermore, a negative relationship was found between the expression level of SLC3A2 and the extent of immune cell infiltration and immune checkpoint. Differentially expressed genes (DEGs) between the high and low SLC3A2 expression groups were primarily involved in cytokine-cytokine receptor interaction and immune response. Finally, in vitro experiments demonstrated that SLC3A2 stimulates tumor cell proliferation and migration.
In conclusion, these results indicated a strong association between SLC3A2 and progression in both NPC and HNSC, suggesting it as a promising biomarker for predicting adverse prognosis in NPC and HNSC patients.
鼻咽癌（NPC）是头颈部最常见的恶性肿瘤之一，其发病机制复杂，预后不良。最近，一种新的细胞死亡形式——二硫键介导的细胞凋亡（disulfidoptosis）被提出。近年来，多项研究广泛探讨了二硫键介导的细胞凋亡相关的溶质载体家族7成员11（SLC7A11）基因在癌症中的作用，但其伴侣蛋白溶质载体家族3成员2（SLC3A2）在鼻咽癌中的作用仍不清楚。
基因表达综合数据库（GEO）分析证实SLC3A2对鼻咽癌有预后影响。受试者工作特征曲线（ROC）、Kaplan-Meier分析和阶段特异性表达研究表明其与头颈部鳞状细胞癌（HNSC）预后不良密切相关。基因本体（GO）和京都基因与基因组百科全书（KEGG）分析确定了相关信号通路。在体外，通过细胞计数试剂盒8（CCK8）、伤口愈合实验、集落形成实验、Transwell实验和细胞周期分析评估SLC3A2对细胞增殖、迁移和侵袭的影响。
在本研究中，我们发现SLC3A2在鼻咽癌和头颈部鳞状细胞癌中高表达，并分析了其潜在机制及其与患者预后的相关性。此外，还发现SLC3A2的表达水平与免疫细胞浸润程度和免疫检查点呈负相关。SLC3A2高表达组和低表达组之间的差异表达基因主要参与细胞因子-细胞因子受体相互作用和免疫反应。最后，体外实验表明SLC3A2可刺激肿瘤细胞增殖和迁移。
总之，这些结果表明SLC3A2与鼻咽癌和头颈部鳞状细胞癌的进展密切相关，提示它有望作为预测鼻咽癌和头颈部鳞状细胞癌患者不良预后的生物标志物。
