The prognostic value of hypoxia-inducible factor-1? in advanced cancer survivors: a meta-analysis with trial sequential analysis.
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ABSTRACT:
SUBMITTER: Han S
PROVIDER: S-EPMC6759726 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
The prognostic value of hypoxia-inducible factor-1α in advanced cancer survivors: a meta-analysis with trial sequential analysis.
Han Susu S Huang Tao T Hou Fenggang F Yao Liting L Wang Xiyu X Wu Xing X
Therapeutic advances in medical oncology 20190924
<h4>Background</h4>Expression of hypoxia-inducible factors (HIFs) has been observed, but their prognostic role in advanced cancers remains uncertain. We conducted a meta-analysis to establish the prognostic effect of HIFs and to better guide treatment planning for advanced cancers.<h4>Methods</h4>Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. Trial sequential analysis (TSA) was also performed. The clinical outcomes included overall survival (OS), disease-free surv ...[more]
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Project description:BackgroundRecently, many studies have shown the role of hypoxia-inducible factor-1α (HIF-1α) expression in the outcome of bone tumor. However, the results remain inconclusive. It is necessary to carry out a meta-analysis of all the current available data to clarify the relationship between HIF-1α and survival or clinicopathological features of bone tumor.MethodsPubMed, Cochrane Library, Web of Science, China National Knowledge Internet, and Wanfang databases were used to search the relationship between HIF-1α and bone tumor. Articles investigating clinicopathological and prognostic value of HIF-1α in bone tumor patients were enrolled in this meta-analysis. Overlapping articles, duplicate data, reviews, case reports, and letters without original data were excluded. The pooled risk ratios (RRs) and hazard ratios (HRs) were used to evaluate the clinicopathological and prognostic value of HIF-1α on bone tumor patients, respectively.ResultsA total of 28 studies including 1443 patients were included in this meta-analysis, which were involved in three different types of bone tumor including 3 chondrosarcomas, 2 giant cell tumors of bone, and 23 osteosarcomas. Our results showed that high expression levels of HIF-1α were associated with poorer OS (overall survival) (HR = 2.61, 95% CI 2.11-3.23, P < 0.001) and shorter DFS (disease-free survival) (HR = 2.02, 95% CI 1.41-2.89, P < 0.001) in bone tumor. In addition, this study also analyzed the role of HIF-1α expression in clinicopathological features, which were closely related with the severity of bone tumor, including differentiation, clinical stage, metastasis, and microvessel density. Our results indicated that HIF-1α overexpression was significantly associated with differentiation (RR = 1.56, 95% CI 1.00-2.43, P = 0.049), clinical stage (RR = 1.75, 95% CI 1.25-2.45, P = 0.001), metastasis (RR = 1.78, 95% CI 1.58-2.00, P < 0.001), and microvessel density (SMD = 2.34, 95% CI 1.35-3.34, P < 0.001) of bone tumor.ConclusionsHIF-1α overexpression indicated an unfavorable factor for OS and DFS in bone tumor, suggesting that HIF-1α may serve as a potential prognostic marker for bone tumor.
| S-EPMC6381668 | biostudies-literature
Project description:Background:Novel prognostic markers and therapeutic targets for advanced cancer are urgently needed. This report with trial sequential analysis (TSA) was first conducted to provide robust estimates of the correlation between aldehyde dehydrogenase 1 (ALDH1) and Nestin and clinical outcomes of advanced cancer patients. Methods:Hazard ratios (HRs) with 95% confidence intervals (CIs) were summarized for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), relapse/recurrence-free survival (RFS), and metastasis-free survival (MFS) from multivariable analysis. TSA was performed to control for random errors. Results:A total of 20 studies with 2050 patients (ALDH1: 15 studies with 1557 patients and Nestin: 5 studies with 493 patients) were identified. ALDH1 (HR = 2.28, p < 0.001) and Nestin (HR = 2.39, p < 0.001) were associated with a worse OS, as confirmed by TSA. Nestin positivity was linked to a poor PFS (HR = 2.08, p < 0.001), but ALDH1 was not linked to DFS, RFS, MFS, or PFS, and TSA showed that more studies were needed. Subgroup analysis by tumor type indicated that ALDH1 positivity may be associated with shorter OS in breast, head and neck cancers, but there was no association with colorectal cancer. Subgroup analysis by study source showed that ALDH1 positivity was correlated with a worse OS for Japanese (HR = 1.94, p = 0.002) and European patients (HR = 4.15, p < 0.001), but there was no association for Chinese patients. Subgroup analysis by survival rate showed that ALDH1 positivity correlated with poor OS at ⩾ 5 years (HR = 2.33, p < 0.001) or 10 years (HR = 1.76, p = 0.038). Conclusions:ALDH1 may be more valuable as an effective therapeutic target than Nestin for improving the long-term survival rate of advanced cancer. Additional prospective clinical trials are needed across different cancer types.
| S-EPMC6393950 | biostudies-literature
Project description:BackgroundCurrent reports on the prognostic and predictive value of hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma are inconsistent. Therefore, we conducted this meta-analysis to precisely evaluate the association of HIF-1α expression with susceptibility, clinical features, and prognosis of endometrial cancer.MethodsEligible studies that assessed the role of HIF-1α protein expression, immunohistochemistry detection, disease susceptibility, clinical features, and prognosis of endometrial cancer were searched from the Embase, Pubmed, and Web of Science databases. Stata 14.0 software was used to merge and compute pooled hazard ratios (HR) and odds ratios (OR). Information including HIF-1α protein expression and clinical progression of endometrial cancer was extracted. The pooled HR and OR with corresponding 95% confidence intervals (CI) were used to estimate the strength of these associations.ResultsA total of 25 studies were included in the analysis. HIF-1α protein expression in endometrial cancer tissue was significantly higher than that in normal tissues (OR = 15.79, 95% CI = 8.44-29.52, P < 0.05). Endometrial cancer patients with higher HIF-1α protein expression had poorer prognosis compared to patients with low HIF-1α protein expression (HR = 2.29, 95% CI = 1.68-2.90, P < 0.05). In addition, high HIF-1α protein expression was significantly associated with endometrial cancer grade, lymph node metastasis, and myometrial invasion (grade in Caucasians: OR = 3.09, 95% CI = 1.63-5.85, P < 0.05; lymph node metastasis: OR = 3.09, 95% CI = 1.63-5.85, P < 0.05; myometrial invasion: OR = 2.26, 95% CI = 2.15-5.08, P < 0.05).ConclusionsHIF-1α overexpression was significantly associated with increased risk, advanced clinical progression, and poor prognosis in endometrial cancer patients.
| S-EPMC7693720 | biostudies-literature
Project description:Objective: Cancer stem cell marker CD44 and its variant isoforms (CD44v) may be correlated with tumor growth, metastasis, and chemo-radiotherapy resistance. However, the prognostic power of CD44 and CD44v in advanced cancer remains controversial. Therefore, the purpose of our study was to generalize the prognostic significance of these cancer stem cell markers in advanced cancer patients. Methods: Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated from multivariable analysis to assess the associations among CD44, CD44v6, and CD44v9 positivity and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and recurrence-free survival (RFS). Trial sequential analysis (TSA) was also conducted. Results: We included 15 articles that reported on 1,201 patients with advanced cancer (CD44: nine studies with 796 cases, CD44v6: three studies with 143 cases, and CD44v9: three studies with 262 cases). CD44 expression was slightly linked to worse OS (HR = 2.03, P = 0.027), but there was no correlation between CD44 expression and DFS, RFS, or PFS. Stratified analysis showed that CD44 expression was not correlated with OS at ≥5 years or OS in patients receiving adjuvant therapy. CD44v6 expression was not associated with OS. CD44v9 expression was closely associated with poor 5-years CSS in patients treated with chemo/radiotherapy (HR = 3.62, P < 0.001). However, TSA suggested that additional trials were needed to confirm these conclusions. Conclusions: CD44 or CD44v9 might be novel therapeutic targets for improving the treatment of advanced cancer patients. Additional prospective clinical trials are strongly needed across different cancer types.
| S-EPMC6372530 | biostudies-literature
Project description:Hypoxia-inducible factor-2? (HIF-2?) plays an important role in tumor progression and metastasis. A number of studies have evaluated the correlation between HIF-2? overexpression and clinical outcome in cancer patients but yielded inconsistent results. To comprehensively and quantitatively summarize the evidence on the capability of HIF-2? to predict the prognosis of cancer patients with solid tumors, a meta-analysis was carried out. Renal cell carcinoma (CC-RCC) was separately analyzed due to an alternative mechanism of regulation. Systematic literature searches were performed in PubMed and Embase databases for relevant original articles until February 2018. Forty-nine studies with 6,052 patients were included in this study. The pooled hazard ratios (HRs) with corresponding confidence intervals were calculated to assess the prognostic value of HIF-2? protein expression in tumor cells. The meta-analysis revealed strong significant negative associations between HIF-2? expression and five endpoints: overall survival [HR?=?1.69, 95% confidence interval (95% CI) 1.39-2.06], disease-free survival (HR?=?1.87, 95% CI 1.2-2.92), disease-specific survival (HR?=?1.57, 95% CI 1.06-2.34), metastasis-free survival (HR?=?2.67, 95% CI 1.32-5.38), and progression-free survival (HR?=?2.18, 95% CI 1.25-3.78). Subgroup analyses revealed similar associations in the majority of tumor sites. Overall, these data demonstrate a negative prognostic role of HIF-2? in patients suffering from different types of solid tumors.
| S-EPMC6004384 | biostudies-literature
Project description:Hypoxia is an important factor in tumor angiogenesis, metastasis, and resistance to chemotherapy or radiotherapy, and may be an indicator of poor prognosis. The transcription factor hypoxia-inducible factor 1 (HIF-1) is the key regulator of the hypoxic state. This study was designed to evaluate the prognostic value of HIF-1α expression in small cell lung cancer (SCLC). Forty-three paraffin-embedded biopsy materials were examined using immunohistochemistry. Our results indicated that the expression of HIF-1α was high in males, and patients with poor Eastern Cooperative Oncology Group (ECOG) performance status and metastases. To elucidate the prognostic value of HIF-1α expression, Kaplan-Meier analysis was carried out and the results showed that patients with high HIF-1α expression had a poorer prognosis than patients with low expression of HIF-1α. After adjusting clinical parameters by the Cox proportional hazards model, our results demonstrated that high HIF-1α expression is an independent prognostic factor for SCLC with a 39.2-fold risk of death (p<0.003). In conclusion, we have provided evidence that HIF-1α expression has significant value in predicting survival of patients with SCLC and is an independent prognostic factor beyond ECOG performance and metastasis status.
| S-EPMC5562133 | biostudies-other
Project description:BackgroundThe results from the published studies on the association between hypoxia-inducible factor -1alpha (HIF-1alpha) polymorphisms and cancer risk are conflicting. In this meta-analysis, we aimed to investigate the association between HIF-1alpha 1772 C/T and 1790 G/A polymorphisms and cancer.MethodsThe meta-analysis for 1772 C/T polymorphism included 4131 cancer cases and 5387 controls, and for 1790 G/A polymorphism included 2058 cancer cases and 3026 controls. Allelic and genotypic comparisons between cases and controls were evaluated. Subgroup analyses by cancer types, ethnicity, and gender were also performed. We included prostate cancer in male subgroup, and female specific cancers in female subgroup.ResultsFor the 1772 C/T polymorphism, the analysis showed that the T allele and genotype TT were significantly associated with higher cancer risk: odds ratio (OR) = 1.29 [95% confidence interval (CI, 1.01, 1.65)], P = 0.04, P(heterogeneity) < 0.00001, and OR = 2.18 [95% CI (1.32, 3.62)], P = 0.003, P(heterogeneity) = 0.02, respectively. The effect of the genotype TT on cancer especially exists in Caucasians and female subjects: OR = 2.40 [95% CI (1.26, 4.59)], P = 0.008, P(heterogeneity) = 0.02, and OR = 3.60 [95% CI (1.17, 11.11)], P = 0.03, P(heterogeneity) = 0.02, respectively. For the 1790 G/A polymorphism, the pooled ORs for allelic frequency comparison and dominant model comparison suggested a significant association of 1790 G/A polymorphism with a decreased breast cancer risk: OR = 0.28 [95% CI (0.08, 0.90)], P = 0.03, P(heterogeneity) = 0.45, and OR = 0.29 [95% CI (0.09, 0.97)], P = 0.04, P(heterogeneity) = 0.41, respectively. The frequency of the HIF-1alpha 1790 A allele was very low and only two studies were included in the breast cancer subgroup.ConclusionsOur meta-analysis suggests that the HIF-1alpha 1772 C/T polymorphism is significantly associated with higher cancer risk, and 1790 G/A polymorphism is significantly associated with decreased breast cancer risk. The effect of the 1772 C/T polymorphism on cancer especially exists in Caucasians and female subjects. Only female specific cancers were included in female subgroup, which indicates that the 1772 C/T polymorphism is significantly associated with an increased risk for female specific cancers. The association between the 1790 G/A polymorphism and lower breast cancer risk could be due to chance.
| S-EPMC2804603 | biostudies-literature
Project description:BACKGROUND:Hypoxia inducible factor 1-alpha (HIF1A) is a transcription factor that plays important role in regulating cascade of reactions. In this study, the effect of rs11549465 (1772 C/T) and rs11549467 (1790 G/A) polymorphisms of HIF1A gene and its association with cancers were investigated through meta-analysis. METHODS:Meta-analysis of genome wide association studies of HIF1A 1772 C/T polymorphism were conducted on 22 case-control studies of sample size 19024 and for 1790 G/A polymorphism 19 case-control studies were included with sample size 10654. Genotype and allelic frequency compared between cases and controls together with further subgroup analyses were carried out by cancer type and ethnicity. RESULTS:Meta-analysis from this study indicated that HIF1A 1772 C/T polymorphism is significantly associated with overall cancer risk. T allele and genotype TT are significantly associated with increasing overall cancer risk; odds ratios (OR) dominant model [TT?+?CT vs. CC: OR 1.30, 95 % CI (1.06-1.59), p-value: 0.0115], and T allele vs. C allele: OR 1.32, 95 % CI (1.07-1.63), p-value: 0.0098. Also, HIF1A 1790 G/A polymorphism, analyses showed that A allele and genotype AA are significantly associated with increasing overall cancer risk; odds ratios (OR) homozygote comparison [AA vs. GG: OR 5.10, 95 % CI (3.12-8.33), p-value: <0.0001], heterozygote comparison [GA vs. GG: OR 1.74, 95 % CI (1.20-2.52), p-value: 0.0033], dominant model [AA?+?GA vs. GG: OR 1.82, 95 % CI (1.26-2.62), p-value: 0.0014], recessive model [AA vs. GA?+?GG: OR 3.79, 95 % CI (2.34-6.15), p-value: <0.0001] and A allele vs. G allele: OR 1.82, 95 % CI (1.31-2.52), p-value: 0.0003. CONCLUSION:In detail meta-analysis indicated that both the polymorphisms 1772 C/T and 1790 G/A are significantly associated with overall cancer risk. The subgroup analyses showed that lung cancer is significantly associated with both polymorphisms. Although the 1772 C/T polymorphism is significantly associated with decreasing risk of renal cell carcinoma but the 1790 G/A polymorphism has shown to significantly increase the cancer risk in both Caucasian and Asian population. Thus, HIF1A could be a useful prognostic marker for cancers early predisposition.
| S-EPMC4693423 | biostudies-literature
Project description:Tissues of symbiotic Cnidarians are exposed to wide, rapid and daily variations of oxygen concentration. Indeed, during daytime, intracellular O2 concentration increases due to symbiont photosynthesis, while during night, respiration of both host cells and symbionts leads to intra-tissue hypoxia. The Hypoxia Inducible Factor 1 (HIF-1) is a heterodimeric transcription factor used for maintenance of oxygen homeostasis and adaptation to hypoxia. Here, we carried out a mechanistic study of the response to variations of O2 concentrations of the coral model Stylophora pistillata. In silico analysis showed that homologs of HIF-1 ? (SpiHIF-1?) and HIF-1? (SpiHIF-1?) exist in coral. A specific SpiHIF-1 DNA binding on mammalian Hypoxia Response Element (HRE) sequences was shown in extracts from coral exposed to dark conditions. Then, we cloned the coral HIF-1? and ? genes and determined their expression and transcriptional activity. Although HIF-1? has an incomplete Oxygen-dependent Degradation Domain (ODD) relative to its human homolog, its protein level is increased under hypoxia when tested in mammalian cells. Moreover, co-transfection of SpiHIF-1? and ? in mammalian cells stimulated an artificial promoter containing HRE only in hypoxic conditions. This study shows the strong conservation of molecular mechanisms involved in adaptation to O2 concentration between Cnidarians and Mammals whose ancestors diverged about 1,200-1,500 million years ago.
| S-EPMC5695583 | biostudies-literature
Project description:BACKGROUND: A meta-analysis was performed to estimate the association between HIF-1? polymorphism (C1772T) and breast cancer risk. MATERIAL AND METHODS: The relevant published literature was retrieved from PubMed, Web of Knowledge, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. RESULTS: Six case-control studies, including 2043 cases and 2146 controls were identified. Meta-analysis showed that there was no marked association between C1772T polymorphism and breast cancer risk in the overall population in the dominant model. The subgroup analysis showed an increased breast cancer risk in Asians based on homozygote comparison and the recessive model. There were no associations between C1772T polymorphism with clinicopathological parameters and habits. CONCLUSIONS: The present meta-analysis suggests that HIF-1? C1772T polymorphism is a risk factor for susceptibility to breast cancer in Asians.
| S-EPMC4266368 | biostudies-literature