Abstract
BACKGROUND: Colon cancer is a prevalent gastrointestinal malignancy that often exhibits distant metastasis, hindering the effectiveness of surgical interventions. In addition to well-known hematogenous and lymphatic metastasis, perineural invasion (PNI) has emerged as a significant mode of distant metastasis in colon tumors. PNI is closely associated with oncologic pain in advanced cancer patients, but the underlying mechanisms and associated biomarkers, which might be the novel therapeutic targets, remain poorly understood. METHODS: In this study, we employed large databases and bioinformatics methods to identify genes strongly linked to PNI in colon cancer and investigated their involvement in tumor nerve invasion, progression mechanisms, and chemotherapy resistance. Immunohistochemical techniques were utilized to validate the expression of target genes in 384 colon cancer tissues, and their expression was correlated with clinicopathological characteristics and patient survival data in our hospital. Furthermore, we conducted a comprehensive literature review to explore the potential functions of the target genes and their associated genes. RESULTS: Our screening revealed a significant correlation between neural proliferation differentiation and control-1 (NPDC1) expression and patient prognosis, suggesting a potential association with neural infiltration in colon cancer. Additionally, NPDC1 may promote tumorigenesis, progression, and chemoresistance through various related pathways. CONCLUSION: Our study provides novel insights into the utility of NPDC1 as a predictive marker for PNI status, disease-free survival, and overall survival in patients with colon cancer, highlighting the prevalence of NPDC1 overexpression in patients with PNI in colon cancer.