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-s...
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| Format: | Article |
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Nature Portfolio
2021-10-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-00727-3 |
| _version_ | 1819119318358556672 |
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| author | Taiichi Wakiya Keinosuke Ishido Norihisa Kimura Hayato Nagase Tadashi Yoshizawa Satoko Morohashi Hiroaki Fujita Taishu Kanda Yota Tatara Junji Saruwatari Hiroshi Kijima Kenichi Hakamada |
| author_facet | Taiichi Wakiya Keinosuke Ishido Norihisa Kimura Hayato Nagase Tadashi Yoshizawa Satoko Morohashi Hiroaki Fujita Taishu Kanda Yota Tatara Junji Saruwatari Hiroshi Kijima Kenichi Hakamada |
| author_sort | Taiichi Wakiya |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T06:02:52Z |
| format | Article |
| id | doaj.art-5645eb4925cb41bcb03a95a00576df20 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T06:02:52Z |
| publishDate | 2021-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5645eb4925cb41bcb03a95a00576df202022-12-21T18:36:30ZengNature PortfolioScientific Reports2045-23222021-10-0111111210.1038/s41598-021-00727-3Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancerTaiichi Wakiya0Keinosuke Ishido1Norihisa Kimura2Hayato Nagase3Tadashi Yoshizawa4Satoko Morohashi5Hiroaki Fujita6Taishu Kanda7Yota Tatara8Junji Saruwatari9Hiroshi Kijima10Kenichi Hakamada11Department of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Pathology and Bioscience, Hirosaki University Graduate School of MedicineDepartment of Pathology and Bioscience, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineDepartment of Stress Response Science, Center for Advanced Medical Research, Hirosaki University Graduate School of MedicineDivision of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto UniversityDepartment of Pathology and Bioscience, Hirosaki University Graduate School of MedicineDepartment of Gastroenterological Surgery, Hirosaki University Graduate School of MedicineAbstract 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.https://doi.org/10.1038/s41598-021-00727-3 |
| spellingShingle | Taiichi Wakiya Keinosuke Ishido Norihisa Kimura Hayato Nagase Tadashi Yoshizawa Satoko Morohashi Hiroaki Fujita Taishu Kanda Yota Tatara Junji Saruwatari Hiroshi Kijima Kenichi Hakamada Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer Scientific Reports |
| title | Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| title_full | Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| title_fullStr | Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| title_full_unstemmed | Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| title_short | Eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| title_sort | eukaryotic initiation factor 2 signaling behind neural invasion linked with lymphatic and vascular invasion in pancreatic cancer |
| url | https://doi.org/10.1038/s41598-021-00727-3 |
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