Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer
Annexin A1 (<i>ANXA1</i>) is a calcium-dependent phospholipid-binding protein overexpressed in pancreatic cancer (PC). <i>ANXA1</i> expression has been shown to take part in a wide variety of cancer biology, including carcinogenesis, cell proliferation, invasion, apoptosis, a...
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MDPI AG
2021-03-01
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| Series: | Cells |
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| author | Masanori Oshi Yoshihisa Tokumaru Swagoto Mukhopadhyay Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe |
| author_facet | Masanori Oshi Yoshihisa Tokumaru Swagoto Mukhopadhyay Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe |
| author_sort | Masanori Oshi |
| collection | DOAJ |
| description | Annexin A1 (<i>ANXA1</i>) is a calcium-dependent phospholipid-binding protein overexpressed in pancreatic cancer (PC). <i>ANXA1</i> expression has been shown to take part in a wide variety of cancer biology, including carcinogenesis, cell proliferation, invasion, apoptosis, and metastasis, in addition to the initially identified anti-inflammatory effect in experimental settings. We hypothesized that <i>ANXA1</i> expression is associated with cell proliferation and survival in PC patients. To test this hypothesis, we analyzed 239 PC patients in The Cancer Genome Atlas (TCGA) and GSE57495 cohorts. <i>ANXA1</i> expression correlated with epithelial–mesenchymal transition (EMT) but weakly with angiogenesis in PC patients. <i>ANXA1</i>-high PC was significantly associated with a high fraction of fibroblasts and keratinocytes in the tumor microenvironment. <i>ANXA1</i> high PC enriched multiple malignant gene sets, including hypoxia, tumor necrosis factor (TNF)-α signaling via nuclear factor-kappa B (NF-kB), and MTORC1, as well as apoptosis, protein secretion, glycolysis, and the androgen response gene sets consistently in both cohorts. <i>ANXA1</i> expression was associated with TP53 mutation alone but associated with all KRAS, p53, E2F, and transforming growth factor (TGF)-β signaling pathways and also associated with homologous recombination deficiency in the TCGA cohort. <i>ANXA1</i> high PC was associated with a high infiltration of T-helper type 2 cells in the TME, with advanced histological grade and <i>MKI67</i> expression, as well as with a worse prognosis regardless of the grade. <i>ANXA1</i> expression correlated with a sensitivity to gemcitabine, doxorubicin, and 5-fluorouracil in PC cell lines. In conclusion, <i>ANXA1</i> expression is associated with EMT, cell proliferation, survival, and the drug response in PC. |
| first_indexed | 2024-03-10T13:13:43Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T13:13:43Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a5589346c2364feb9bc38de0cb1772a92023-11-21T10:34:43ZengMDPI AGCells2073-44092021-03-0110365310.3390/cells10030653Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic CancerMasanori Oshi0Yoshihisa Tokumaru1Swagoto Mukhopadhyay2Li Yan3Ryusei Matsuyama4Itaru Endo5Kazuaki Takabe6Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USADepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, JapanDepartment of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Kanagawa 236-0004, JapanDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USAAnnexin A1 (<i>ANXA1</i>) is a calcium-dependent phospholipid-binding protein overexpressed in pancreatic cancer (PC). <i>ANXA1</i> expression has been shown to take part in a wide variety of cancer biology, including carcinogenesis, cell proliferation, invasion, apoptosis, and metastasis, in addition to the initially identified anti-inflammatory effect in experimental settings. We hypothesized that <i>ANXA1</i> expression is associated with cell proliferation and survival in PC patients. To test this hypothesis, we analyzed 239 PC patients in The Cancer Genome Atlas (TCGA) and GSE57495 cohorts. <i>ANXA1</i> expression correlated with epithelial–mesenchymal transition (EMT) but weakly with angiogenesis in PC patients. <i>ANXA1</i>-high PC was significantly associated with a high fraction of fibroblasts and keratinocytes in the tumor microenvironment. <i>ANXA1</i> high PC enriched multiple malignant gene sets, including hypoxia, tumor necrosis factor (TNF)-α signaling via nuclear factor-kappa B (NF-kB), and MTORC1, as well as apoptosis, protein secretion, glycolysis, and the androgen response gene sets consistently in both cohorts. <i>ANXA1</i> expression was associated with TP53 mutation alone but associated with all KRAS, p53, E2F, and transforming growth factor (TGF)-β signaling pathways and also associated with homologous recombination deficiency in the TCGA cohort. <i>ANXA1</i> high PC was associated with a high infiltration of T-helper type 2 cells in the TME, with advanced histological grade and <i>MKI67</i> expression, as well as with a worse prognosis regardless of the grade. <i>ANXA1</i> expression correlated with a sensitivity to gemcitabine, doxorubicin, and 5-fluorouracil in PC cell lines. In conclusion, <i>ANXA1</i> expression is associated with EMT, cell proliferation, survival, and the drug response in PC.https://www.mdpi.com/2073-4409/10/3/653ANXA1biomarkergene setGSEAmetastasispancreatic cancer |
| spellingShingle | Masanori Oshi Yoshihisa Tokumaru Swagoto Mukhopadhyay Li Yan Ryusei Matsuyama Itaru Endo Kazuaki Takabe Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer Cells ANXA1 biomarker gene set GSEA metastasis pancreatic cancer |
| title | Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer |
| title_full | Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer |
| title_fullStr | Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer |
| title_full_unstemmed | Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer |
| title_short | Annexin A1 Expression Is Associated with Epithelial–Mesenchymal Transition (EMT), Cell Proliferation, Prognosis, and Drug Response in Pancreatic Cancer |
| title_sort | annexin a1 expression is associated with epithelial mesenchymal transition emt cell proliferation prognosis and drug response in pancreatic cancer |
| topic | ANXA1 biomarker gene set GSEA metastasis pancreatic cancer |
| url | https://www.mdpi.com/2073-4409/10/3/653 |
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