The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis

Han, Susu; Huang, Tao; Hou, Fenggang; Yao, Liting; Wang, Xiyu; Wu, Xing

doi:10.1177/1758835919875851

Cited by 20 publications

(18 citation statements)

References 70 publications

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“…cancer meta-analyses(95,96). The relative risks of high expression of HIF-1, MVD, VEGF, CA9, and other hypoxic markers are only moderate compared to known clinical prognostic factors that already represent the aggressive phenotype associated with HIFs (e.g.…”

mentioning

confidence: 99%

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

237

146

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Hypoxia-inducible factors (HIFs) and the HIF-dependent cancer hallmarks angiogenesis and metabolic rewiring are well-established drivers of breast cancer aggressiveness, therapy resistance, and poor prognosis. Targeting of HIF and its downstream targets in angiogenesis and metabolism has been unsuccessful so far in the breast cancer clinical setting, with major unresolved challenges residing in target selection, development of robust biomarkers for response prediction, and understanding and harnessing escape mechanisms. This Review discusses the pathophysiological role of HIFs, angiogenesis, and metabolism in breast cancer and the challenges of targeting these features in breast cancer patients. Rational therapeutic combinations, especially with immunotherapy and endocrine therapy, seem most promising in the clinical exploitation of the intricate interplay of HIFs, angiogenesis, and metabolism in breast cancer cells and the tumor microenvironment.

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mentioning

confidence: 99%

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Heer¹,

Jalving²,

Harris³

2020

Journal of Clinical Investigation

237

146

View full text Add to dashboard Cite

show abstract

“…Moreover, HIF-1α expression has been associated with worse prognosis in advanced cancer patients treated with chemotherapy and/or radiotherapy; thus, in addition to a useful biomarker, targeting HIF-1α could be an interesting therapeutic approach to improve survival in advanced cancer patients. 68 Here, significant results were observed in some clinicopathological features, including BCLC staging, capsule infiltration, intrahepatic metastasis, lymph node metastasis, TNM classification, tumor differentiation, tumor number, tumor size (contrasting greater or less than 3 cm), vascular invasion and vasculogenic mimicry. After subgroup analysis according to sample size and NOS score, we also observed a possible HIF-1α correlation with AFP levels, cirrhosis, tumor size (5 cm) and albumin, while histological grade showed association after removing one study.…”

Section: Discussionmentioning

confidence: 79%

Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis

et al. 2021

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Background: Hepatocellular carcinoma (HCC) is a highly recurrent tumor after resection and has been closely related to hypoxia. Hypoxia-inducible factors 1α and 2α (HIF-1α and HIF-2α) have been shown to contribute to tumor progression and therapy resistance in HCC. We evaluated the prognostic and clinicopathological significance of HIF-1α and HIF-2α in HCC patients. Methods: We systematically searched Embase, Cochrane, PubMed, Scopus and Web of Science (WOS) from inception to 1 June 2020 for studies evaluating HIF-1α and/or HIF-2α expression in HCC. Selected articles evaluate at least one factor by immunohistochemistry (IHC) in HCC patients who underwent surgical resection, and its relationship with prognosis and/or clinicopathological features. Study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CDR42020191977). We meta-analyzed the data extracted or estimated according to the Parmar method employing STATA software. We evaluated the overall effect size for the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI), as well as heterogeneity across studies with the I2 statistic and chi-square-based Q test. Moreover, we conducted subgroup analysis when heterogeneity was substantial. Publication bias was assessed by funnel plot asymmetry and Egger’s test. Results: HIF-1α overexpression was correlated with overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and clinicopathological features including Barcelona Clinic Liver Cancer (BCLC), capsule infiltration, intrahepatic metastasis, lymph node metastasis, tumor–node–metastasis (TNM), tumor differentiation, tumor number, tumor size (3 cm), vascular invasion and vasculogenic mimicry. We also detected a possible correlation of HIF-1α with alpha-fetoprotein (AFP), cirrhosis, histological grade, tumor size (5 cm) and albumin after subgroup analysis. Initially, only DFS/RFS appeared to be associated with HIF-2α overexpression. Subgroup analysis denoted that HIF-2α overexpression was related to OS and capsule infiltration. Conclusions: HIF-1α and HIF-2α overexpression is related to poor OS, DFS/RFS and some clinicopathological features of HCC patients, suggesting that both factors could be useful HCC biomarkers.

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“…Increased HIF1 expression is associated with overall poorer survival in breast cancer patients [ 169 ], and several studies directly or indirectly implicate HIF1-α in the diabetes-breast cancer crosstalk. A study conducted in 2015, reported HIF1 mediated advancement of breast metastasis in comorbid patients [ 170 ], however the article cannot be fully reviewed, as it was excluded based on language discrepancy.…”

Section: Hif1’s Regulation Of the Multilayered Relationship Between T2dm And Breast Cancermentioning

confidence: 99%

The prognostic outcome of ‘type 2 diabetes mellitus and breast cancer’ association pivots on hypoxia-hyperglycemia axis

2021

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Type 2 diabetes mellitus and breast cancer are complex, chronic, heterogeneous, and multi-factorial diseases; with common risk factors including but not limited to diet, obesity, and age. They also share mutually inclusive phenotypic features such as the metabolic deregulations resulting from hyperglycemia, hypoxic conditions and hormonal imbalances. Although, the association between diabetes and cancer has long been speculated; however, the exact molecular nature of this link remains to be fully elucidated. Both the diseases are leading causes of death worldwide and a causal relationship between the two if not addressed, may translate into a major global health concern. Previous studies have hypothesized hyperglycemia, hyperinsulinemia, hormonal imbalances and chronic inflammation, as some of the possible grounds for explaining how diabetes may lead to cancer initiation, yet further research still needs to be done to validate these proposed mechanisms. At the crux of this dilemma, hyperglycemia and hypoxia are two intimately related states involving an intricate level of crosstalk and hypoxia inducible factor 1, at the center of this, plays a key role in mediating an aggressive disease state, particularly in solid tumors such as breast cancer. Subsequently, elucidating the role of HIF1 in establishing the diabetes-breast cancer link on hypoxia-hyperglycemia axis may not only provide an insight into the molecular mechanisms underlying the association but also, illuminate on the prognostic outcome of the therapeutic targeting of HIF1 signaling in diabetic patients with breast cancer or vice versa. Hence, this review highlights the critical role of HIF1 signaling in patients with both T2DM and breast cancer, potentiates its significance as a prognostic marker in comorbid patients, and further discusses the potential prognostic outcome of targeting HIF1, subsequently establishing the pressing need for HIF1 molecular profiling-based patient selection leading to more effective therapeutic strategies emerging from personalized medicine.

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The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis

Cited by 20 publications

References 70 publications

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

HIFs, angiogenesis, and metabolism: elusive enemies in breast cancer

Prognostic and clinicopathological significance of hypoxia-inducible factors 1α and 2α in hepatocellular carcinoma: a systematic review with meta-analysis

The prognostic outcome of ‘type 2 diabetes mellitus and breast cancer’ association pivots on hypoxia-hyperglycemia axis

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