Perineural invasion-associated biomarkers for tumor development

Perineural invasion (PNI) is the process of neoplastic invasion of peripheral nerves and is considered to be the fifth mode of cancer metastasis. PNI has been detected in head and neck tumors and pancreatic, prostate, bile duct, gastric, and colorectal cancers. It leads to poor prognostic outcomes and high local recurrence rates. Despite the increasing number of studies on PNI, targeted therapeutic modalities have not been proposed. The identification of PNI-related biomarkers would facilitate the non-invasive and early diagnosis of cancers, the establishment of prognostic panels, and the development of targeted therapeutic approaches. In this review, we compile information on the molecular mediators involved in PNI-associated cancers. The expression and prognostic significance of molecular mediators and their receptors in PNI-associated cancers are analyzed, and the possible mechanisms of action of these mediators in PNI are explored, as well as the association of cells in the microenvironment where PNI occurs.