铜死亡相关基因与 Jab1 相关，可重塑鼻咽癌肿瘤微环境和药理学特征。
Cuproptosis related genes associated with Jab1 shapes tumor microenvironment and pharmacological profile in nasopharyngeal carcinoma.
机构信息
Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, Hubei, China.
Department of Clinical Pathology, Houjie Hospital of Dongguan, the Affiliated Houjie Hospital of Guangdong Medical University, Dongguan, China.
出版信息
Front Immunol. 2022 Dec 23;13:989286. doi: 10.3389/fimmu.2022.989286. eCollection 2022.
BACKGROUND
Nasopharyngeal carcinoma (NPC) is the most common subcategory of head and neck squamous cell carcinoma (HNSCC). This study focused on the roles of cuproptosis related genes and Jab1 in the tumor microenvironment of NPC and HNSCC.
METHODS
Differential expression analysis of Jab1 and cuproptosis related genes in tumor cell enriched region (PanCK-expressing) and immune cell enriched region (CD45-expressing) of NPC microenvironment were performed by packages of R software. Survival analysis was performed using the survival and survminer packages. Corrplot package was used for correlation analysis. ConsensusClusterPlus package was used for cluster clustering among different regions of NPC, and functional enrichment analysis was performed using GSVA, GSEABase, clusterProfiler, org.Hs.eg.db and enrichplot packages. The pRRophetic package was used to predict drug sensitivity in NPC and HNSCC.
RESULTS
Relationships exist between cuproptosis related genes and Jab1 in the NPC microenvironment. The expression of cuproptosis related genes and Jab1 differed between tumor cell enriched region and immune cell enriched region. AKT inhibitor VIII, Doxorubicin, Bleomycin and Etoposide showed higher sensitivity to tumor cell than immune cell. In the high Jab1 group, higher expression of ATP7A, DBT, DLD and LIAS were associated with better prognosis of HNSCC patients. In contrast, in the low Jab1 group, higher expression of these genes is associated with worse prognosis of HNSCC patients.
CONCLUSIONS
Prognostic cuproptosis related genes and Jab1 provided a basis for targeted therapy and drug development.
背景
鼻咽癌（NPC）是头颈部鳞状细胞癌（HNSCC）中最常见的亚类。本研究专注于 NPC 和 HNSCC 肿瘤微环境中 cuproptosis 相关基因和 Jab1 的作用。
方法
使用 R 软件包对 NPC 微环境中肿瘤细胞富集区（PanCK 表达）和免疫细胞富集区（CD45 表达）中的 Jab1 和 cuproptosis 相关基因进行差异表达分析。使用 survival 和 survminer 包进行生存分析。使用 Corrplot 包进行相关性分析。使用 ConsensusClusterPlus 包对 NPC 不同区域进行聚类聚类，并使用 GSVA、GSEABase、clusterProfiler、org.Hs.eg.db 和 enrichplot 包进行功能富集分析。使用 pRRophetic 包预测 NPC 和 HNSCC 中的药物敏感性。
结果
NPC 微环境中 cuproptosis 相关基因与 Jab1 之间存在关系。cuproptosis 相关基因和 Jab1 的表达在肿瘤细胞富集区和免疫细胞富集区之间存在差异。AKT 抑制剂 VIII、阿霉素、博来霉素和依托泊苷对肿瘤细胞的敏感性高于免疫细胞。在高 Jab1 组中，ATP7A、DBT、DLD 和 LIAS 的高表达与 HNSCC 患者的较好预后相关。相反，在低 Jab1 组中，这些基因的高表达与 HNSCC 患者的较差预后相关。
结论
预后 cuproptosis 相关基因和 Jab1 为靶向治疗和药物开发提供了依据。
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