Tumor innervation in cervical cancer: Prognostic insights from myelin-associated risk signatures

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.