Peng Shixiong, Wang Jinhang, Hei Naiheng, Cui Zifeng
Department of stomatology, The Fourth Hospital of Hebei Medical University, Jiankang Road 12, Shijiazhuang, 050011, Hebei, China.
Department of Stomatology, The Second Hospital of Shijiazhuang, Huaxi Road 53, Shijiazhuang, 050051, Hebei, China.
J Cancer. 2024 Jun 3;15(13):4156-4174. doi: 10.7150/jca.95515. eCollection 2024.
Epithelial Cell Transforming Sequence 2 (ECT2) has been implicated in various tumorigenic processes, including proliferation, migration, and invasion. However, its specific role in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study integrates transcriptomic and single-cell RNA sequencing (scRNA-seq) data to explore the potential role of ECT2 in HNSCC. Differential expression analysis, cell-based assays (including CCK-8 for proliferation, transwell for migration, invasion assays, and flow cytometry for apoptosis and cell cycle analysis), and enrichment analysis were employed to investigate ECT2 expression levels and its regulatory effects on cellular phenotypes. Additionally, Mendelian randomization analysis was utilized to identify genes causally related to HNSCC using publicly available Genome-Wide Association Study (GWAS) data. ECT2 is highly expressed in HNSCC samples and its downregulation inhibits proliferation, migration, invasion, induces apoptosis, and affects the cell cycle transition in HSC-3 cells. Furthermore, differential analysis revealed significant differences in the immune microenvironment and drug sensitivity between high and low ECT2 expression groups. The pathways enriched in different groups include CCR and its related chemokines, as well as HLA in antigen presentation and immune response. There are also significant differences in the sensitivity to drugs such as bortezomib and dasatinib between the two groups. Prognostic models constructed from prognosis-related genes showed significant differences in prognosis between high and low-risk groups. Integration of scRNA-seq data identified Monocyte clusters as high-scoring cell clusters based on genes interacting with ECT2.Mendelian randomization analysis identified three genes (LGALS2, SLC11A1, and TKT) causally related to HNSCC within this cell cluster. Conclusion: The findings suggest that ECT2 overexpression is associated with the survival rate of HNSCC, indicating its potential as a prognostic biomarker for this malignancy.
上皮细胞转化序列2（ECT2）与包括增殖、迁移和侵袭在内的多种致瘤过程有关。然而，其在头颈部鳞状细胞癌（HNSCC）中的具体作用仍不清楚。本研究整合转录组和单细胞RNA测序（scRNA-seq）数据，以探索ECT2在HNSCC中的潜在作用。采用差异表达分析、基于细胞的实验（包括用于增殖的CCK-8、用于迁移的Transwell、侵袭实验以及用于凋亡和细胞周期分析的流式细胞术）和富集分析来研究ECT2的表达水平及其对细胞表型的调节作用。此外，利用孟德尔随机化分析，通过公开可用的全基因组关联研究（GWAS）数据来识别与HNSCC因果相关的基因。ECT2在HNSCC样本中高表达，其下调可抑制HSC-3细胞的增殖、迁移、侵袭，诱导凋亡并影响细胞周期转变。此外，差异分析显示ECT2高表达组和低表达组在免疫微环境和药物敏感性方面存在显著差异。不同组中富集的通路包括CCR及其相关趋化因子，以及抗原呈递和免疫反应中的HLA。两组之间对硼替佐米和达沙替尼等药物的敏感性也存在显著差异。由预后相关基因构建的预后模型显示高风险组和低风险组在预后方面存在显著差异。scRNA-seq数据的整合将单核细胞簇识别为基于与ECT2相互作用的基因的高分细胞簇。孟德尔随机化分析在该细胞簇中确定了三个与HNSCC因果相关的基因（LGALS2、SLC11A1和TKT）。结论：研究结果表明ECT2过表达与HNSCC的生存率相关，表明其作为这种恶性肿瘤预后生物标志物的潜力。
