Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma
Abstract Pancreatic cancer (PC) is a highly malignant tumor with an extremely poor prognosis, but early diagnosis and treatment can significantly improve prognosis. This study aimed to screen autophagy-related exosome genes associated with poor prognosis in PC and to explore the underlying mechanism...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer
2025-07-01
|
| Series: | Discover Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1007/s12672-025-03061-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849334608338878464 |
|---|---|
| author | Lunbing Liang Pengcheng Guo Mingming Xiao Fuqiang Zu Guoliang Hao Chaochun Zhang Qingfeng Liu |
| author_facet | Lunbing Liang Pengcheng Guo Mingming Xiao Fuqiang Zu Guoliang Hao Chaochun Zhang Qingfeng Liu |
| author_sort | Lunbing Liang |
| collection | DOAJ |
| description | Abstract Pancreatic cancer (PC) is a highly malignant tumor with an extremely poor prognosis, but early diagnosis and treatment can significantly improve prognosis. This study aimed to screen autophagy-related exosome genes associated with poor prognosis in PC and to explore the underlying mechanisms in malignant progression via bioinformatics analysis to provide a reference for the diagnosis, treatment and prognosis evaluation of PC, especially pancreatic ductal adenocarcinoma (PDAC). Matrix files of 178 PC tissues (including 143 PDAC) and 167 healthy human pancreatic tissues and clinical data were downloaded from the UCSC Xena database, exosome database (exoRbase) and autophagy database (HADb), and the relevant mechanisms were explored by bioinformatics methods, including differential analysis, LASSO regression analysis, survival analysis, functional analysis, immune infiltration analysis and drug sensitivity analysis. Finally, the expression of related genes in PDAC was verified via immunohistochemistry. Our research results indicate that the autophagy-related exosome genes PTK6, ITGA3 and ITGB4 are independent risk factors for PC and may promote PC development and invasion by promoting cell–cell adhesion and cell–matrix adhesion, inhibiting tumor cell autophagy, promoting nerve infiltration, reducing CD8 + T-cell content, and increasing M0 and M2 macrophage content. Drug susceptibility analysis showed that crizotinib, tamoxifen, ixazomib, and carboplatin had inhibitory effects on ITGA3, ITGB4, and PTK6. |
| format | Article |
| id | doaj-art-53ba84969ac246da83c6cd22cb14d7f3 |
| institution | Kabale University |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-53ba84969ac246da83c6cd22cb14d7f32025-08-20T03:45:31ZengSpringerDiscover Oncology2730-60112025-07-0116112010.1007/s12672-025-03061-6Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinomaLunbing Liang0Pengcheng Guo1Mingming Xiao2Fuqiang Zu3Guoliang Hao4Chaochun Zhang5Qingfeng Liu6General Surgery, People’s Hospital of Liaoning Province, China Medical UniversityGeneral Surgery, People’s Hospital of Liaoning Province, Dalian Medical UniversityThe Pathology Department, People’s Hospital of Liaoning ProvinceDepartment of General Surgery, The Second Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityGeneral Surgery, People’s Hospital of Liaoning Province, China Medical UniversityGeneral Surgery, People’s Hospital of Liaoning Province, China Medical UniversityGeneral Surgery, JinQiu Hospital of LiaoNing ProvinceAbstract Pancreatic cancer (PC) is a highly malignant tumor with an extremely poor prognosis, but early diagnosis and treatment can significantly improve prognosis. This study aimed to screen autophagy-related exosome genes associated with poor prognosis in PC and to explore the underlying mechanisms in malignant progression via bioinformatics analysis to provide a reference for the diagnosis, treatment and prognosis evaluation of PC, especially pancreatic ductal adenocarcinoma (PDAC). Matrix files of 178 PC tissues (including 143 PDAC) and 167 healthy human pancreatic tissues and clinical data were downloaded from the UCSC Xena database, exosome database (exoRbase) and autophagy database (HADb), and the relevant mechanisms were explored by bioinformatics methods, including differential analysis, LASSO regression analysis, survival analysis, functional analysis, immune infiltration analysis and drug sensitivity analysis. Finally, the expression of related genes in PDAC was verified via immunohistochemistry. Our research results indicate that the autophagy-related exosome genes PTK6, ITGA3 and ITGB4 are independent risk factors for PC and may promote PC development and invasion by promoting cell–cell adhesion and cell–matrix adhesion, inhibiting tumor cell autophagy, promoting nerve infiltration, reducing CD8 + T-cell content, and increasing M0 and M2 macrophage content. Drug susceptibility analysis showed that crizotinib, tamoxifen, ixazomib, and carboplatin had inhibitory effects on ITGA3, ITGB4, and PTK6.https://doi.org/10.1007/s12672-025-03061-6Pancreatic cancerExosomesAutophagyIntegrins α3Integrin β4Protein tyrosine kinase 6 |
| spellingShingle | Lunbing Liang Pengcheng Guo Mingming Xiao Fuqiang Zu Guoliang Hao Chaochun Zhang Qingfeng Liu Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma Discover Oncology Pancreatic cancer Exosomes Autophagy Integrins α3 Integrin β4 Protein tyrosine kinase 6 |
| title | Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma |
| title_full | Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma |
| title_fullStr | Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma |
| title_short | Prognostic analysis and mechanistic exploration of the autophagy-related exosome genes ITGA3, ITGB4, and PTK6 in pancreatic ductal adenocarcinoma |
| title_sort | prognostic analysis and mechanistic exploration of the autophagy related exosome genes itga3 itgb4 and ptk6 in pancreatic ductal adenocarcinoma |
| topic | Pancreatic cancer Exosomes Autophagy Integrins α3 Integrin β4 Protein tyrosine kinase 6 |
| url | https://doi.org/10.1007/s12672-025-03061-6 |
| work_keys_str_mv | AT lunbingliang prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT pengchengguo prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT mingmingxiao prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT fuqiangzu prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT guolianghao prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT chaochunzhang prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma AT qingfengliu prognosticanalysisandmechanisticexplorationoftheautophagyrelatedexosomegenesitga3itgb4andptk6inpancreaticductaladenocarcinoma |