Chen Guoqiang, Zheng Zhen, Ji Qingqing, He Ruihua, Pan Zhouyuan, Chen Yunxia, Zhou Yuqing, Wei Zhihong, Sun Hao, Feng Lixia
Department of Gynecology The People's Hospital of Baoan Shenzhen, The Second Affiliated Hospital of Shenzhen University Shenzhen China.
Department of Obstetrics and Gynecology National Clinical Research Centre for Obstetric and Gynecologic Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.
FASEB Bioadv. 2025 Apr 23;7(5):e70004. doi: 10.1096/fba.2024-00190. eCollection 2025 May.
The reported frequencies of perineural invasion (PNI) in human cervical cancer, ranging from 7.0% to 35.1%, may underestimate the significant role that nerves play in cervical cancer progression. Neurosecretory factors can promote tumor migration and invasion, even in cases classified as "PNI-negative". This study aimed to clarify whether tumor innervation influences tumor progression and cervical cancer patient outcomes. We first evaluated the gene signatures of human myelinating Schwann cells (SCs) using the Inferring Pathway Activity and Suppression (IPAS) scoring system to predict the degree of tumor innervation in 304 cervical cancer patients from The Cancer Genome Atlas (TCGA) database. Subsequently, we constructed a myelin-associated risk prognostic signature using LASSO regression analysis. Finally, we obtained a risk score using a quantitative formula and categorized all samples into high- and low-risk score groups. Our results indicated that tumor innervation in cervical cancer is associated with poor patient survival. Higher levels of innervation were correlated with an impaired immune response and reduced expression of immune checkpoints, including PD-L1. The prognostic model demonstrated excellent consistency between predicted and actual survival outcomes. Overall, tumor innervation plays a crucial role in regulating cervical cancer prognosis. The identified prognostic risk signatures offer a valuable tool for risk stratification and prognostic prediction in clinical practice.
据报道，人类宫颈癌中神经周围浸润（PNI）的发生率在7.0%至35.1%之间，这可能低估了神经在宫颈癌进展中所起的重要作用。神经分泌因子可促进肿瘤迁移和侵袭，即使在分类为“PNI阴性”的病例中也是如此。本研究旨在阐明肿瘤神经支配是否影响肿瘤进展和宫颈癌患者的预后。我们首先使用推断通路活性和抑制（IPAS）评分系统评估人类有髓施万细胞（SCs）的基因特征，以预测来自癌症基因组图谱（TCGA）数据库的304例宫颈癌患者的肿瘤神经支配程度。随后，我们使用LASSO回归分析构建了一个髓鞘相关风险预后特征。最后，我们使用定量公式获得风险评分，并将所有样本分为高风险评分组和低风险评分组。我们的结果表明，宫颈癌中的肿瘤神经支配与患者的不良生存相关。较高水平的神经支配与免疫反应受损和免疫检查点（包括PD-L1）表达降低相关。预后模型在预测生存结果和实际生存结果之间表现出极好的一致性。总体而言，肿瘤神经支配在调节宫颈癌预后中起关键作用。所确定的预后风险特征为临床实践中的风险分层和预后预测提供了一个有价值 的工具。
