Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer

Shih, Ho-Jun; Chang, Hsin-Fang; Chen, Chi‐Ling; Torng, Pao-Ling

doi:10.1038/s41598-021-02400-1

Cited by 16 publications

(12 citation statements)

References 46 publications

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“…HIF-2α plays an important role in cancer aggressiveness by regulating angiogenesis, invasion, and metastasis that accelerates EOC progression. 16 The hypoxia-induced HIF-1α also affects the expression of genes involved in the formation of metastases. Hepatocyte growth factor (HGF) for example is a cytokine that stimulates proliferation and invasion through its receptor, the proto-oncogene c-MET.…”

Section: Discussionmentioning

confidence: 99%

Association Hypoxia Inducible Factors-1 Alpha (HIF-1 α) Levels and Epithelial Ovarian Cancer (EOC)

Asis

2023

Obgynia

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Objective: This study was conduct to investigate the association of the HIF-1α with stage,hystological type of ephitelial ovarian cancer (EOC). Methods: This study is an observational study with a cross-sectional design on 72 women diagnosed with epithelial ovarian carcinoma who underwent surgical staging in a period of 2017 to 2019 in Wahidin Sudirohusodo Hospital. Measurement of HIF1a concentration was performed and further categorized into weak, moderate and strong and then analyzed with age, parity, history of abortion, ascites, type of histopathology, cancer stage and CA-125 serum level. Result: There’s a significant relationship between HIF-1a expression and stage (p<0.05), where moderate expression of HIF1a was the most dominant with a total of 32 (44.4%) people. Moderate-to-strong expression of HIF1a was found more in patients with epithelial ovarian carcinoma than weak-to-negative HIF1a expression. More patients with stage III-IV ovarian carcinoma were found with moderate-to-strong HIF1a expression (51 people). Conclusion: HIF1a expression was found to be increased along with the progression of epithelial ovarian cancer stage where positive HIF1a expression was found more in patients with stage III/IV compared to stage I/II. Hubungan Antara Kadar Hypoxia Inducible Factors-1 Alpha (HIF-1 α) dengan Karsinoma Ovarium Tipe Epitelial Abstrak Tujuan: Penelitian ini bertujuan untuk mengetahui hubungan antara kadar HIF-1 alpha dan karsinoma ovarium tipe epithelial Metode: Penelitian ini menggunakan desain case-control pada 72 perempuan dengan karsinoma ovarium tipe epitelial yang telah menjalani surgical staging selama tahun 2017 hingga 2019 di RS Wahidin Sudirohusodo. Peneliti mengukur kadar HIF1a dan mengkategorikan dalam negatif, lemah, sedang, dan kuat serta menilai hubungannya dengan usia, paritas, riwayat abortus, ascites, jenis histologi, stadium kanker ovarium, dan kadar CA-125. Hasil: Terdapat hubungan antara stadium dan ekspresi HIF1a (p<0.05). HIF1a dengan ekspresi-sedang didapatkan paling banyak yaitu 32 (44.4%) orang. Lebih banyak ditemukan ekspresi HIF1a sedang-kuat pada pasien karsinoma ovarium tipe epithelial dibandingkan ekspresi HIF1a negatif-lemah. Pasien karsinoma ovarium stadium 3-4 lebih banyak ditemukan dengan ekspresi HIF1a sedang-kuat (51 orang). Kesimpulan: Terdapat hubungan yang bermakna antara ekspresi HIF1a dan stadium kanker ovarium tipe epitelial yaitu ekspresi positif HIF1a lebih banyak ditemukan pada pasien dengan stadium III/IV dibandingkan stadium I/II. Kata kunci: Karsinoma ovarium tipe epitelial, Hypoxia Inducible Factor 1 alpha (HIF1a), stadium kanker

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Section: Discussionmentioning

confidence: 99%

Association Hypoxia Inducible Factors-1 Alpha (HIF-1 α) Levels and Epithelial Ovarian Cancer (EOC)

Asis

2023

Obgynia

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“…This can explain the antitumorigenic effects of HIF-1α in cancers with low MYC oncogenic dependency and demonstrates the complexity of HIF-α in highly MYC oncogenic cancers, suggesting that solely inhibiting HIF-1α may result in preliminary attenuation, but have no impact on overall tumor burden [ 273 ]. Shih et al [ 274 ] demonstrated that HIF-2α was critical for tumor re-proliferation, i.e., the switch from tumor dormancy to proliferation, in epithelial ovarian cancer cells. In addition, a comparison of the acute hypoxic response while HIF-2α mediates the chronic response then initial proliferation and subsequent reoxygenation due to rapid proliferation would be predominantly controlled by HIF-1α.…”

Section: The Hif-α Debatementioning

confidence: 99%

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Davis

Recktenwald

Hutt

et al. 2022

Cancers

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Inadequate oxygen supply, or hypoxia, is characteristic of the tumor microenvironment and correlates with poor prognosis and therapeutic resistance. Hypoxia leads to the activation of the hypoxia-inducible factor (HIF) signaling pathway and stabilization of the HIF-α subunit, driving tumor progression. The homologous alpha subunits, HIF-1α and HIF-2α, are responsible for mediating the transcription of a multitude of critical proteins that control proliferation, angiogenic signaling, metastasis, and other oncogenic factors, both differentially and sequentially regulating the hypoxic response. Post-translational modifications of HIF play a central role in its behavior as a mediator of transcription, as well as the temporal transition from HIF-1α to HIF-2α that occurs in response to chronic hypoxia. While it is evident that HIF-α is highly dynamic, HIF-2α remains vastly under-considered. HIF-2α can intensify the behaviors of the most aggressive tumors by adapting the cell to oxidative stress, thereby promoting metastasis, tissue remodeling, angiogenesis, and upregulating cancer stem cell factors. The structure, function, hypoxic response, spatiotemporal dynamics, and roles in the progression and persistence of cancer of this HIF-2α molecule and its EPAS1 gene are highlighted in this review, alongside a discussion of current therapeutics and future directions.

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“…During tumor progression, oxygen deficiency and accumulation of metabolic products lead to hypoxia and acidity in the TME ( 110 ). Hypoxia in the TME induces the production of hypoxia-inducible factors (HIFs), which promote pro-angiogenic factors secreted by ECs, thereby promoting angiogenesis ( 111 ). In the course of angiogenesis, factors produced by cancer cells contain VEGF, platelet derived growth factor (PDGF), fibroblast growth factor 2 (FGF-2) and angiopoietins ( 112 ).…”

Section: Tumor Microenvironmentmentioning

confidence: 99%

Therapeutic implications of the tumor microenvironment in ovarian cancer patients receiving PD-1/PD-L1 therapy

Wang

Zhang²,

Bai

et al. 2022

Front. Immunol.

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Epithelial ovarian cancer (EOC) ranks as the second most common cause of gynecologic cancer death. The conventional treatment for patients with EOC is postoperative therapy along with platinum chemotherapy. However, a more efficient treatment regimen is of great need for these patients diagnosed with advanced disease (FIGO stages III–IV), whose survival is approximately 29%. Immunotherapy seems to be an encouraging therapeutic strategy for EOC. Given the crucial role in the complicated interactions between tumor cells and other cells, the tumor microenvironment (TME) influences the response to immunotherapy. In this review, we discuss feasible strategies for EOC immunotherapy by exploiting the reciprocity of cancer cells and the constituents of the TME.

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Differential expression of hypoxia-inducible factors related to the invasiveness of epithelial ovarian cancer

Cited by 16 publications

References 46 publications

Association Hypoxia Inducible Factors-1 Alpha (HIF-1 α) Levels and Epithelial Ovarian Cancer (EOC)

Association Hypoxia Inducible Factors-1 Alpha (HIF-1 α) Levels and Epithelial Ovarian Cancer (EOC)

Targeting HIF-2α in the Tumor Microenvironment: Redefining the Role of HIF-2α for Solid Cancer Therapy

Therapeutic implications of the tumor microenvironment in ovarian cancer patients receiving PD-1/PD-L1 therapy

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