Tumor innervation in cervical cancer: More is worse

Background: The nervous system plays a significant role in tumor growth and metastasis. However, the low frequencies of perineural invasion reported in previous studies on human cervical cancer — ranging from 7.0% to 35.1% of cases — may overlook the active role that nerves play in cervical cancer progression. Neurosecretory factors can promote tumor migration and invasion, even in cases classified as “PNI-negative”. Therefore, this study aims to clarify whether tumor innervation influences tumor progression and patient outcomes. Methods: We evaluated the gene signatures of human myelinating Schwann cells using the IPAS scoring system to predict the degree of tumor innervation in 304 cervical cancer patients from the TCGA database. Subsequently, we constructed a myelin-associated risk prognostic signature by LASSO regression analysis. Finally, we obtained a risk score by a quantitative formula and divided all samples into high- and low- risk score groups. Results: Our results indicated that tumor innervation in cervical cancer was associated with poor patient survival. Higher levels of innervation correlated with an impaired immune response and reduced expression of immune checkpoints, including PD-1. The prognostic model demonstrated excellent consistency between predictions and actual survival outcomes. Conclusions: Tumor innervation plays a crucial role in the regulation of prognosis in cervical cancer, and the identified risk prognostic signatures offer a valuable tool for risk stratification and prognostic prediction in clinical practice.