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PD-L2调控EMT影响头颈部鳞状细胞癌转移的机制研究
The mechanism study of PD-L2 influencing metastasis of head and neck squamous cell carcinoma via regulating EMT
【摘要】 目的:探讨程序性死亡受体配体2(programmed death-ligand 2,PD-L2)和上皮间充质转化(epithelial-mesenchymal transition,EMT)相关指标在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)中的特征性表达及其影响HNSCC转移的机制。方法:收集2018年1月至2023年7月天津医科大学肿瘤医院94例HNSCC患者肿瘤组织样本,免疫组织化学染色评估PD-L2蛋白的表达水平,统计评估其与淋巴结转移等临床病理参数的相关性。Western blot实验检测HNSCC中PD-L2的表达水平。慢病毒载体构建过表达和敲除PD-L2的稳转单克隆细胞系,Transwell实验探究PD-L2对HNSCC细胞系的侵袭迁移的影响。RNA测序技术确定受PD-L2调控的下游靶基因。通过Western blot分析检测E-cadherin、N-cadherin和Vimentin等关键EMT标志物的表达水平,以阐明PD-L2通过激活EMT通路促进肿瘤细胞转移的分子机制。结果:HNSCC中PD-L2高表达与N分期呈正相关(P<0.05),并且PD-L2高表达预示HNSCC患者预后不良。结论:PD-L2调控EMT促进HNSCC转移,靶向PD-L2有望成为治疗转移性HNSCC新策略。
【Abstract】 Objective: This study aimed to investigate the characteristic expression of programmed death-ligand 2(PD-L2) and epithelialmesenchymal transition(EMT)-related biomarkers in head and neck squamous cell carcinoma(HNSCC) and their mechanism of action in HNSCC metastasis. Methods: Tumor tissue samples from 94 patients with HNSCC were collected from Tianjin Medical University Cancer Hospital from January 2018 to July 2023, and their correlation with clinicopathological parameters, including lymph node metastasis, was statistically assessed. Western blot was used to detect PD-L2 expression in HNSCC tumor tissues. PD-L2 overexpression and knockdown stablytransfected monoclonal cell lines were generated using lentiviral vectors. Transwell assays were performed to explore the effect of PD-L2 on the invasive migration of the HNSCC cell lines. Additionally, RNA sequencing was used to identify downstream target genes regulated by PDL2. The expression levels of key EMT markers, including E-cadherin, N-cadherin, and Vimentin, were examined by Western blot to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through EMT pathway activation. Additionally, RNA sequencing was employed to identify downstream target genes regulated by PD-L2. The expression levels of key EMT markers, including E-cadherin, Ncadherin, and Vimentin, were examined with Western blot analysis to elucidate the molecular mechanism by which PD-L2 promotes tumor cell metastasis through the EMT pathway activation. Results: High expression of PD-L2 is positively correlated with N staging(P<0.05), and elevated PD-L2 expression predicts a poor prognosis in HNSCC patients. Conclusions: PD-L2 regulates the EMT pathway to promote HNSCC metastasis. Targeting PD-L2 is expected to provide a new strategy for the treatment of metastatic HNSCC.
【Key words】 head and neck squamous cell carcinoma(HNSCC); programmed death-ligand 2(PD-L2); epithelial-mesenchymal transition(EMT); metastasis;
- 【文献出处】 中国肿瘤临床 ,Chinese Journal of Clinical Oncology , 编辑部邮箱 ,2025年11期
- 【分类号】R739.91
- 【下载频次】5