Won Seongjun, Hah Young-Sool, Cheon So Young, Yim Chae Dong, Park Sang-Wook, Lee Seung-Jun, Seo Ji Hyun, Park Jung Je
Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University College of Medicine, Jinju, Republic of Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Gyeongsang National University Hospital, Jinju, Republic of Korea.
Anticancer Res. 2025 Jul;45(7):3099-3115. doi: 10.21873/anticanres.17674.
BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a significant global health burden, with a modest 5-year survival rate; therefore, novel therapeutic targets are needed. Periostin, an extracellular matrix protein, is implicated in tumor progression, yet its role in OSCC, particularly epithelial-mesenchymal transition (EMT), is poorly understood.
We investigated periostin's role in OSCC using a multifaceted approach: retrospective analysis of 97 OSCC patient samples, bioinformatics analyses of GEO and TCGA datasets, and / experiments using the HNSCC-31 cell line and xenograft mouse models. Periostin expression was assessed immunohistochemistry and western blotting. Functional effects were evaluated through cell viability, colony formation, migration, invasion, and EMT marker expression assays following periostin over-expression (Ad-POSTN), knockdown (Lenti-shPOSTN) or recombinant periostin treatment.
Periostin expression was significantly elevated in OSCC tissue compared than normal tissue (<0.001) and correlated with lymph node metastasis (=0.011), higher AJCC stage (=0.008), and recurrence (=0.001). High periostin levels independently predicted poor disease-free [hazard ratio (HR)=2.329, =0.019] and overall survival (HR=2.842, =0.009). , periostin up-regulation enhanced viability, colony formation, migration, and invasion, and EMT (increased vimentin, Snail, MMP-9, N-cadherin; decreased E-cadherin), while knockdown reversed these effects. , Ad-POSTN xenografts were significantly larger (<0.05) and heavier (<0.05) and showed increased periostin expression histologically.
Periostin promotes OSCC progression by enhancing invasiveness and metastasis EMT. It represents a potential prognostic marker and therapeutic target. These findings highlight the need for further clinical validation of periostin-targeted therapies for management of OSCC.
背景/目的:口腔鳞状细胞癌(OSCC)是一项重大的全球健康负担,其5年生存率一般;因此,需要新的治疗靶点。骨膜蛋白是一种细胞外基质蛋白,与肿瘤进展有关,但其在OSCC中的作用,尤其是上皮-间质转化(EMT),尚不清楚。
我们采用多方面方法研究骨膜蛋白在OSCC中的作用:对97例OSCC患者样本进行回顾性分析,对GEO和TCGA数据集进行生物信息学分析,以及使用HNSCC-31细胞系和异种移植小鼠模型进行实验。通过免疫组织化学和蛋白质印迹法评估骨膜蛋白表达。在骨膜蛋白过表达(Ad-POSTN)、敲低(Lenti-shPOSTN)或重组骨膜蛋白处理后,通过细胞活力、集落形成、迁移、侵袭和EMT标志物表达测定评估功能效应。
与正常组织相比,OSCC组织中骨膜蛋白表达显著升高(<0.001),并与淋巴结转移(=0.011)、较高的AJCC分期(=0.008)和复发(=0.001)相关。高骨膜蛋白水平独立预测无病生存期差[风险比(HR)=2.329,=0.019]和总生存期差(HR=2.842,=0.009)。此外,骨膜蛋白上调增强了活力、集落形成、迁移和侵袭以及EMT(波形蛋白、Snail、MMP-9、N-钙黏蛋白增加;E-钙黏蛋白减少),而敲低则逆转了这些效应。此外,Ad-POSTN异种移植瘤明显更大(<0.05)且更重(<0.05),并且在组织学上显示骨膜蛋白表达增加。
骨膜蛋白通过增强侵袭性和转移以及EMT促进OSCC进展。它代表一种潜在的预后标志物和治疗靶点。这些发现凸显了对骨膜蛋白靶向治疗用于OSCC管理进行进一步临床验证的必要性。