Hypoxia inducible factor‐1 alpha plays a pivotal role in hepatic metastasis of pancreatic cancer: an immunohistochemical study
Abstract
Background: Hypoxia is an important condition to promote angiogenesis that is essential to tumor progression, including pancreatic ductal adenocarcinoma ( PDAC ). We evaluated whether the immunohistochemistry for hypoxia inducible factor‐1α ( HIF ‐1α) was correlated with hepatic metastases in PDAC . Methods: We examined the expression of HIF ‐1α, vascular endothelial growth factor‐ A ( VEGF ‐ A ), thymidine phosphorylase ( TP ) and basic fibroblast growth factor ( bFGF ) in a total of 100 paraffin‐embedded PDAC primary tumors using immunohistochemical staining, and assessed their clinicopathological correlations. We determined microvessel count ( MVC ) and apoptotic index ( AI ), and assessed their correlations with hepatic metastases. Student's t ‐test, the M ann– W hitney U ‐test, and S pearman correlation coefficients were used to validate the model, and regression analysis was used to test the model. Results: Hypoxia inducible factor‐1α expression induced the expression of multiple angiogenic factors, leading to a higher MVC and a lower AI . HIF ‐1α expression ( P = 0.0087) and angiogenic factors ( P = 0.0079) were significantly associated with not only the microvessel status ( P = 0.022) but also the high incidence of hepatic metastasis ( P = 0.02), resulting in the worse survival of PDAC patients ( P < 0.05). Conclusions: Hypoxia inducible factor‐1α plays a pivotal role in hepatic metastasis through its association with the expression of angiogenic factors in PDAC patients. These results may contribute future therapeutic strategies to prevent pancreatic cancer metastasis.
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High HIF-1 expression is associated with metastasis in patients with gynecological, pancreatic, esophageal, lung, and prostate cancers.
“Immunohistochemical analysis of human primary tumor samples has revealed an association between high HIF-1 expression and metastasis in patients with gynecological, pancreatic, esophageal, lung, and prostate cancers”
From Hypoxic control of metastasis (2016) · cites this paper as [37]
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- Authors
- Matsuo, Y., Ding, Q., Desaki, R., Maemura, K., Mataki, Y., Shinchi, H., Natsugoe, S., & Takao, S.
- Affiliations
- Kagoshima University (JP)
- Corresponding author
- Takao, Sonshin
- Venue
- Journal of Hepato-Biliary-Pancreatic Sciences
- Publisher
- Wiley
- Published
- 2013-06-20
- Volume
- 21
- Issue
- 2
- Pages
- 105-112
- ISSN
- 1868-6974 (ISSN-L)
- 1868-6982
- OpenAlex
- W2149415725
- Cited by
- 50
- References
- 42
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 3 · 2016: 6 · 2015: 5 · 2014: 6 · 2013: 1
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepato-Biliary-Pancreatic Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- hypoxia-inducible factor-1α, pancreatic ductal adenocarcinoma, liver metastasis, tumor angiogenesis, VEGF-A, thymidine phosphorylase, basic fibroblast growth factor, microvessel count, apoptosis, patient survival
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Humans, Immunohistochemistry, Liver Neoplasms, Male, Middle Aged, Pancreatic Neoplasms, Pyrimidines, Sulfonamides, Thymidine Phosphorylase, Fibroblast Growth Factor 2, In Situ Nick-End Labeling, Vascular Endothelial Growth Factor A, Hypoxia-Inducible Factor 1, alpha Subunit, Microvessels
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