The Correlation of Expression Levels of HIF-1  and HIF-2  in Hepatocellular Carcinoma with Capsular Invasion, Portal Vein Tumor Thrombi and Patients' Clinical Outcome

Yang, Shengli; Liu, Liping; Jiang, Jianxin; Xiong, Zhifan; He, Qian‐Jin; Wu, Chao

doi:10.1093/jjco/hyt194

Cited by 55 publications

(65 citation statements)

References 31 publications

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“…Sun et al (11) demonstrated that a high expression of HIF2α induces apoptosis through the TFDP3/E2F1 pathway and correlates with an increased overall survival. Notably, Yang et al (12) identified no association between HIF2α and clinicopathological characteristics, overall and disease-free survival. The results of the present study were similar to those of Yang et al (12).…”

Section: Hif2α ------------------------------------------------------mentioning

confidence: 99%

“…A number of studies have reported that HIF2α overexpression is associated with poor prognosis (8-10), however Sun et al (11) reported the opposite results. Previously, Yang et al (12) revealed that there was no correlation between HIF2α and prognosis in patients with HCC.…”

Section: Introductionmentioning

confidence: 99%

“…HIF1α and HIF2α are highly expressed in a number of types of cancer, indicating the important roles of these HIFs. However, the role of HIF2α in HCC remains controversial (8)(9)(10)(11)(12). A number of studies have reported that HIF2α overexpression is associated with poor prognosis (8-10), however Sun et al (11) reported the opposite results.…”

Section: Introductionmentioning

confidence: 99%

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Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

et al. 2017

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Abstract. Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P= 0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

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Section: Hif2α ------------------------------------------------------mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

et al. 2017

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“…Although sorafenib is first choice of treatment for advanced HCC, it has been reported that this systemic drug has limited benefits and poor response rates (22,23). Solid tumors contain hypoxic cells, which exhibit resistance to antitumor treatments due to an enhanced cellular adaptive response to hypoxia, mediated by HIF-1α and HIF-2α, which promotes survival (14,(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

“…Solid tumors contain hypoxic cells, which exhibit resistance to antitumor treatments due to an enhanced cellular adaptive response to hypoxia, mediated by HIF-1α and HIF-2α, which promotes survival (14,(24)(25)(26). HIF-1α synthesis is suppressed following treatment with sorafenib, which results in the altered hypoxic response from HIF-1α to HIF-2α-dependent pathways; this mechanism was reported to result in more aggressive tumor growth (22,23). In the present study, it was demonstrated that targeted HIF-2α knock-down inhibited HCC cell proliferation under hypoxic conditions in vitro; in addition, this acted synergistically with sorafenib to further suppress the growth of HCC tumors in vivo.…”

Section: Discussionmentioning

confidence: 99%

Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma

Liu

Dong

et al. 2015

Oncology Letters

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Abstract. Sorafenib is a type of multikinase inhibitor that exhibits antiangiogenic and antiproliferative effects; in addition, sorafenib is a unique first-line drug recommended for the treatment of advanced hepatocellular carcinoma (HCC). However, the effectiveness of HCC treatment remains poor due to acquired drug resistance. It has been suggested that hypoxia, induced as a results of the antiangiogenic effects of sustained sorafenib treatment, may be an important factor in sorafenib resistance. The transcription factor hypoxia-inducible factor (HIF)-2α has been reported to be associated with cell proliferation under hypoxic conditions; therefore, it was hypothesized that hypoxia may enhance tumor cell proliferation via this mechanism. The present study aimed to evaluate whether the knock-down of HIF-2α was able to enhance the therapeutic efficacy of sorafenib in order to effectively treat HCC. The results demonstrated that hypoxia protected HCC cells against sorafenib; however, short hairpin RNA-HIF-2α transfection in combination with sorafenib treatment exhibited a significantly synergistic effect against HCC cell proliferation. In addition, HCC cells acquired increased β-catenin/C-Myc expression, which enhanced proliferation under hypoxic conditions; however, targeted knock-down of HIF-2α or C-Myc markedly decreased cell proliferation in HCC cells. In conclusion, the results of the present study indicated that the targeted knock-down of HIF-2α in combination with sorafenib may be a promising strategy for the treatment of HCC.

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DCE‐MRI for early evaluation of therapeutic response in esophageal cancer after concurrent chemoradiotherapy and its values in predicting HIF‐1α expression

Xie

Guo

et al. 2021

Precision Medical Sciences

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To examine the feasibility of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the early assessment of the therapeutic response to concurrent chemoradiotherapy (CRT) in esophageal cancer (EC) patients and to determine its value in predicting HIF-1α expression. EC patients underwent DCE-MRI 1 week pre-CRT and 3 weeks post-CRT (3w-CRT). According to tumor regression post-treatment, patients were divided into sensitive group (SG) and resistant group (RG). HIF-1α expression was assessed by immunohistochemistry (IHC). Quantitative parameters (ktrans, kep, and ve) were compared between the SG and RG groups, as well as between the HIF-1α(+) and HIF-1α(À) groups. Receiver operating characteristic (ROC) curve analysis was performed to detect the best predictor of the above parameters in the therapeutic response and in predicting HIF-1α expression.Totally 34 and 5 patients were included in the SG and RG, respectively. Pre-ktrans and pre-kep were decreased significantly in the SG at 3w-CRT (p < .01), whereas only pre-kep was decreased in the RG (p = .037). Pre-ktrans was higher in the SG compared with the RG (p < .01). Meanwhile, absolute Δktrans (post-ktrans-pre-ktrans) was reduced more substantially in the SG compared with the RG. Δktrans also had the highest area under the curve (AUC = 0.929) in distinguishing SG from RG. Based on IHC, 13 and 11 patients were HIF-1α(+) and HIF-1α(À), respectively. At 3w-CRT, post-ktrans was markedly lower than pre-ktrans in the HIF-1α(+) group (p < .01); however, both ktrans and kep in the HIF-1α(À) group were dramatically reduced than pre-treatment values (both p < .01). Pre-ktrans was significantly higher in the HIF-1α (À) group compared with the HIF-1α(+) group (p = .002) and constituted an excellent Xiaodong Xie and Lingling Gu contributed equally to this study.

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The Correlation of Expression Levels of HIF-1 and HIF-2 in Hepatocellular Carcinoma with Capsular Invasion, Portal Vein Tumor Thrombi and Patients' Clinical Outcome

Cited by 55 publications

References 31 publications

Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

Association of PHD3 and HIF2α gene expression with clinicopathological characteristics in human hepatocellular carcinoma

Targeting hypoxia-inducible factor-2α enhances sorafenib antitumor activity via β-catenin/C-Myc-dependent pathways in hepatocellular carcinoma

DCE‐MRI for early evaluation of therapeutic response in esophageal cancer after concurrent chemoradiotherapy and its values in predicting HIF‐1α expression

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