H. Takahashi1, E. Katsuta1, K. Takabe1 1Roswell Park Cancer Institute,Surgical Oncology,Buffalo, NY, USA
Introduction:
Perineural invasion (PNI) is the process of neoplastic invasion of nerves, and is a morphologic feature observed in various malignancies. It serves as one of the pathologically determined poor prognostic factors along with lymphovascular invasion, and also can be a source of distant metastasis for some tumors. PNI is widely prevalent in patients with pancreatic ductal adenocarcinoma (PDAC). Although the exact mechanism of invasion to nerve still remains unclear, several signaling pathways in tumor microenvironment (TME) have been reported to date. Since PNI is relatively subjective pathological evaluation, there have been some conflicting reports of utility of PNI in the management of PDAC. Therefore, in the present study, we aimed to identify biological factors that are associated with PNI in PDAC using publicly available large data set The Cancer Genome Atlas (TCGA).
Methods:
Genomic and clinical data of patients with PDAC were obtained from TCGA through cBioportal. Pathological information associated with TCGA was obtained through TIES. Using Kaplan-Meier survival curve and Cox proportional hazards model, clinical and oncologic parameters were analyzed. Gene Set Enrichment Analysis (GSEA) was also conducted between the groups based on PNI status.
Results:
There were 154 patients with PDAC in TCGA. The mean age of the cohort was 65.1 years old, with 83 (54%) patients being male. PNI was positive in 109 patients (71%), negative in 13 (8%), and unknown in 32 (21%). There was no significant difference in overall survival (OS) based on PNI status in TCGA cohort. Median OS was 17.8 months in PNI positive, and 19.9 months in negative (p=0.30). Subsequently, in order to identify the risk factors for OS, univariate analysis was performed with multiple clinical parameters. There was significantly longer OS in the patients who underwent adjuvant radiation therapy or targeted molecular therapy (p=0.002 and p<0.001, respectively). With multivariate analysis, absence of targeted molecular therapy (Hazard Ratio (HR): 4.76, p<0.001), absence of adjuvant radiation (HR: 2.58, p=0.02), and positive PNI (HR: 8.28, p=0.02) were found as independent risk factors of poor prognosis in patients with PDAC.
Furthermore, the PNI positive group was identified to enrich angiogenesis gene set by GSEA (NES: 1.67, p=0.002).
Conclusion:
Positive PNI was one of independent risk factors of poor prognosis in patients with PDAC in this study. It might be due to the associated angiogenesis and possible distant metastasis.