Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Otorhinolaryngology, Fujian Provincial Hospital, Fuzhou, China.
J Gene Med. 2024 Jan;26(1):e3653. doi: 10.1002/jgm.3653.
Nasopharyngeal carcinoma (NPC) is a highly aggressive and metastatic malignancy originating in the nasopharyngeal tissue. Pyroptosis is a relatively newly discovered, regulated form of necrotic cell death induced by inflammatory caspases that is associated with a variety of diseases. However, the role and mechanism of pyroptosis in NPC are not fully understood.
We analyzed the differential expression of pyroptosis-related genes (PRGs) between patients with and without NPC from the GSE53819 and GSE64634 datasets of the Gene Expression Omnibus (GEO) database. We mapped receptor operating characteristic profiles for these key PRGs to assess the accuracy of the genes for disease diagnosis and prediction of patient prognosis. In addition, we constructed a nomogram based on these key PRGs and carried out a decision curve analysis. The NPC patients were classified into different pyroptosis gene clusters by the consensus clustering method based on key PRGs, whereas the expression profiles of the key PRGs were analyzed by applying principal component analysis. We also analyzed the differences in key PRGs, immune cell infiltration and NPC-related genes between the clusters. Finally, we performed differential expression analysis for pyroptosis clusters and obtained differentially expressed genes (DEGs) and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.
We obtained 14 differentially expressed PRGs from GEO database. Based on these 14 differentially expressed PRGs, we applied least absolute shrinkage and selection operator analysis and the random forest algorithm to obtain four key PRGs (CHMP7, IL1A, TP63 and GSDMB). We completely distinguished the NPC patients into two pyroptosis gene clusters (pyroptosis clusters A and B) based on four key PRGs. Furthermore, we determined the immune cell abundance of each NPC sample, estimated the association between the four PRGs and immune cells, and determined the difference in immune cell infiltration between the two pyroptosis gene clusters. Finally, we obtained and functional enrichment analyses 259 DEGs by differential expression analysis for both pyroptosis clusters.
PRGs are critical in the development of NPC, and our research on the pyroptosis gene cluster may help direct future NPC therapeutic approaches.
鼻咽癌（NPC）是一种起源于鼻咽组织的高度侵袭性和转移性恶性肿瘤。细胞焦亡是一种由炎症半胱天冬酶诱导的新型调节性细胞坏死形式，与多种疾病有关。然而，细胞焦亡在 NPC 中的作用和机制尚不完全清楚。
我们从基因表达综合数据库（GEO）的 GSE53819 和 GSE64634 数据集分析了 NPC 患者和无 NPC 患者之间细胞焦亡相关基因（PRG）的差异表达。我们绘制了这些关键 PRG 的受体工作特征曲线，以评估这些基因对疾病诊断和预测患者预后的准确性。此外，我们基于这些关键 PRG 构建了一个列线图，并进行了决策曲线分析。根据关键 PRG 对 NPC 患者进行共识聚类，将其分为不同的细胞焦亡基因簇，应用主成分分析分析关键 PRG 的表达谱。我们还分析了不同细胞焦亡基因簇之间关键 PRG、免疫细胞浸润和 NPC 相关基因的差异。最后，我们对细胞焦亡簇进行差异表达分析，获得差异表达基因（DEG），并进行基因本体论和京都基因与基因组百科全书富集分析。
我们从 GEO 数据库中获得了 14 个差异表达的 PRG。基于这 14 个差异表达的 PRG，我们应用最小绝对收缩和选择算子分析和随机森林算法，获得了 4 个关键 PRG（CHMP7、IL1A、TP63 和 GSDMB）。我们完全根据这 4 个关键 PRG 将 NPC 患者分为两个细胞焦亡基因簇（细胞焦亡簇 A 和 B）。此外，我们确定了每个 NPC 样本的免疫细胞丰度，估计了这 4 个 PRG 与免疫细胞的关联，并确定了两个细胞焦亡基因簇之间免疫细胞浸润的差异。最后，我们通过对两个细胞焦亡簇的差异表达分析获得了 259 个差异表达基因，并进行了功能富集分析。
PRG 在 NPC 的发生发展中起着关键作用，我们对细胞焦亡基因簇的研究可能有助于指导未来 NPC 的治疗方法。
