Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer.

Abstract

Perineural invasion (PNI) is a typical poor prognostic factor in pancreatic ductal adenocarcinoma (PDAC). The mechanisms linking PNI to poor prognosis remain unclear. This study aimed to clarify what changes occurred alongside PNI in PDAC. A 128-patient cohort undergoing surgery for early-stage PDAC was evaluated. Subdivided into two groups, according to pathological state, a pancreatic nerve invasion (ne) score of less than three (from none to moderate invasion) was designated as the low-grade ne group. The high-grade (marked invasion) ne group (74 cases, 57.8%) showed a higher incidence of lymphatic metastasis (P = 0.002), a higher incidence of early recurrence (P = 0.004), decreased RFS (P < 0.001), and decreased DSS (P < 0.001). The severity of lymphatic (r = 0.440, P = 0.042) and venous (r = 0.610, P = 0.002) invasions was positively correlated with the ne score. Tumors having abundant stroma often displayed severe ne. Proteomics identified eukaryotic initiation factor 2 (EIF2) signaling as the most significantly enriched pathway in high-grade ne PDAC. Additionally, EIF2 signaling-related ribosome proteins decreased according to severity. Results showed that PNI is linked with lymphatic and vascular invasion in early-stage PDAC. Furthermore, the dysregulation of proteostasis and ribosome biogenesis can yield a difference in PNI severity.

• Authors: Taiichi Wakiya, Keinosuke Ishido, Norihisa Kimura, Hayato Nagase, Tadashi Yoshizawa, Satoko Morohashi, Hiroaki Fujita, Taishu Kanda, Yota Tatara, Junji Saruwatari, Hiroshi Kijima, Kenichi Hakamada
• Journal: Scientific reports (Sci Rep) Vol. 11 Issue 1 Pg. 21197 (10 27 2021) ISSN: 2045-2322 [Electronic] England
• PMID: 34707166 (Publication Type: Journal Article, Observational Study)
• Copyright: © 2021. The Author(s).

Chemical References

• Biomarkers, Tumor
• Eukaryotic Initiation Factor-2
• Proteome
• Ribosomal Proteins

Topics

• Aged
• Aged, 80 and over
• Biomarkers, Tumor (metabolism)
• Eukaryotic Initiation Factor-2 (metabolism)
• Female
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Pancreatic Neoplasms (metabolism, pathology)
• Proteome (genetics, metabolism)
• Ribosomal Proteins (metabolism)
• Signal Transduction