Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue—influence of a modulated host stroma on the prognosis of HCC

Simon, Frank A.; Bockhorn, Maximilian; Praha, Christian; Baba, Hideo A.; Broelsch, Christoph E.; Frilling, Andrea; Weber, Frank

doi:10.1007/s00423-009-0590-9

Cited by 38 publications

(29 citation statements)

References 32 publications

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“…prognosis, relative to patients with low HIF1α. 27 In conclusion, it appears that HIF1α, but not HIF2α, activation plays an important pro-tumorogenic role in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 81%

Metabolic reprogramming and two-compartment tumor metabolism

et al. 2012

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Section: Discussionmentioning

confidence: 81%

Metabolic reprogramming and two-compartment tumor metabolism

et al. 2012

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“…In these cases, high-level expression of HIF-1a was observed in more than 60% of HCC tissues, which correlated with poor patient prognosis [73]. Interestingly, elevated HIF-1a transcript levels in adjacent non-tumorous liver tissues correlated with poor disease-free and overall survival of HCC patients, indicating a paracrine effect of hypoxia even on non-tumorous cells [74].…”

Section: Hypoxia-inducible Factor-1 (Hif-1)mentioning

confidence: 99%

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Malz

Pinna

Schirmacher

et al. 2012

Journal of Hepatology

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Hepatocellular carcinoma (HCC) is one of the most frequent human malignancies with poor prognosis and increasing incidence in the Western world. Only for a minority of HCC patients, surgical treatment options offer potential cure and therapeutic success of pharmacological approaches is limited. Highly specific approaches (e.g., kinase inhibitors) did not significantly improve the situation so far, possibly due to functional compensation, genetic heterogeneity of HCC, and development of resistance under selective pressure. In contrast, transcriptional regulators (especially transcription factors and co-factors) may integrate and process input signals of different (oncogenic) pathways and therefore represent cellular bottlenecks that regulate tumor cell biology. In this review, we want to summarize the current knowledge about central transcriptional regulators in human hepatocarcinogenesis and their potential as therapeutic target structures. Genomic and transcriptomic data of primary human HCC revealed that many of these factors showed up in subgroups of HCCs with a more aggressive phenotype, suggesting that aberrant activity of transcriptional regulators collect input information to promote tumor initiation and progression. Therefore, expression and dysfunction of transcription factors and co-factors may gain relevance for diagnostics and therapy of HCC.

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“…43,45 Hif-1a mRNA and protein expression in tumor specimens 49 has been shown to be significantly associated with lower levels of Hif-1a transcript in their surrounding nonmalignant tissue, correlating with better 1-and 5-year disease-free survival (DFS). 50 Interestingly, a connection between Hif-1a and HBx protein expression was observed in a case series of 72 hepatitis B virus (HBV)-related HCCs, where worse disease-free and OS was predicted by stronger Hif-1a immunopositivity. 51 An independent effect of patients' mortality from HCC has also been noted in patients displaying higher Hif-2a immunolabeling.…”

Section: Hypoxia-inducible Factorsmentioning

confidence: 99%

Tissue Biomarkers of Prognostic Significance in Hepatocellular Carcinoma

Pinato

Pirisi

Maslen

et al. 2014

Advances in Anatomic Pathology

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Despite major advancements in the clinical management of hepatocellular carcinoma (HCC), the natural history of this disease is characterized by an invariably poor prognosis. However, there are significant interindividual variations in the biologic behavior of this tumor and this combined with the confounding effect of liver function on patient survival makes prognostic prediction particularly difficult. Several studies have attempted to investigate the prognostic role of tissue biomarkers to better understand the molecular basis of HCC progression. These studies have looked at several aspects of cancer biology including proliferative potential, invasive capacity, and angiogenic promotion utilizing different methodologies. The aim of this review is to summarize the role of tissue biomarkers in the prognostic prediction of HCC and to outline questions and strategies in the prognostic assessment of HCC.

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Deregulation of HIF1-alpha and hypoxia-regulated pathways in hepatocellular carcinoma and corresponding non-malignant liver tissue—influence of a modulated host stroma on the prognosis of HCC

Cited by 38 publications

References 32 publications

Metabolic reprogramming and two-compartment tumor metabolism

Metabolic reprogramming and two-compartment tumor metabolism

Transcriptional regulators in hepatocarcinogenesis – Key integrators of malignant transformation

Tissue Biomarkers of Prognostic Significance in Hepatocellular Carcinoma

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