Liu Qian, Peng Yuanhao, Liu Wenbin, Luo Xiangjian
Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China.
Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, PR China.
PLoS One. 2025 Jul 24;20(7):e0329007. doi: 10.1371/journal.pone.0329007. eCollection 2025.
Cervical cancer remains the second leading cause of female cancer mortality worldwide, with metastasis representing a critical therapeutic challenge. This study systematically reveals the key role of SERPINH1 (Serpin Family H Member 1) as a hub regulator of malignant progression in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Through analysis of TCGA-CESC datasets, we identified that high SERPINH1 expression is significantly correlated with poor prognosis and contributes to tumor progression by promoting cell proliferation, invasion, and metastatic phenotypes. In vitro experiments validated these findings, demonstrating that SERPINH1 overexpression markedly enhanced the proliferation, invasion, and metastasis of cervical cancer cells, whereas its knockdown substantially inhibited these processes. Furthermore, based on the SERPINH1-related differentially expressed genes, a prognostic risk model was constructed, successfully identifying PLOD1, ITGA5, and ESM1 as core collaborative genes affecting patient prognosis. Overall, our findings underscore the multiple functions of SERPINH1 as a hub for cervical cancer metastasis regulation, suggesting its potential as a promising biomarker for tailoring strategies in metastasis patients of CESC.
宫颈癌仍是全球女性癌症死亡的第二大主要原因,转移是一个关键的治疗挑战。本研究系统地揭示了丝氨酸蛋白酶抑制剂H1(SERPINH1)作为宫颈鳞状细胞癌和宫颈内膜腺癌(CESC)恶性进展的枢纽调节因子的关键作用。通过对TCGA-CESC数据集的分析,我们发现SERPINH1高表达与预后不良显著相关,并通过促进细胞增殖、侵袭和转移表型促进肿瘤进展。体外实验验证了这些发现,表明SERPINH1过表达显著增强了宫颈癌细胞的增殖、侵袭和转移,而其敲低则显著抑制了这些过程。此外,基于与SERPINH1相关的差异表达基因,构建了一个预后风险模型,成功地将PLOD1、ITGA5和ESM1鉴定为影响患者预后的核心协同基因。总体而言,我们的研究结果强调了SERPINH1作为宫颈癌转移调节枢纽的多种功能,表明其作为CESC转移患者定制策略的有前景生物标志物的潜力。