Iron metabolism gene expression and prognostic features of hepatocellular carcinoma

Shen, Ying; Li, Xin; Zhao, Bin; Xue, Yanru; Wang, Shenghang; Chen, Xin; Yang, Juhua; Lv, Huanhuan; Shang, Peng

doi:10.1002/jcb.27184

Cited by 65 publications

(57 citation statements)

References 53 publications

(115 reference statements)

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“…An abnormal form of NTBI, called labile plasma iron or reactive plasma iron, also contributes to oxidative stress and the subsequent liver damage during HH [105] . Overall, several studies support the role of iron-induced ROS formation as the main mechanism of development of HCC in HH [32,80,99,106,107] .…”

Section: Mechanisms Of Iron Toxicity In Hh Leading To Hccmentioning

confidence: 72%

“…Iron is ubiquitously present in cells and a physiological optimal balance of iron is critical for the normal functioning of cells [79,80] . Iron is essential for several important processes including the transfer of oxygen throughout the body by haemoglobin, the mitochondrial electron transport chain and as a cofactor in enzymatic reactions.…”

Section: Mechanisms Of Iron Toxicity In Hh Leading To Hccmentioning

confidence: 99%

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Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Jayachandran¹,

Shrestha²,

Bridle³

et al. 2020

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Hepatocellular carcinoma (HCC) is a significant global health problem with high morbidity and mortality. Its incidence is increasing exponentially worldwide with a close overlap between annual incidence and death rates. Even though significant advances have been made in HCC treatment, fewer than 20% of patients with HCC are suitable for potentially curative treatment. Hereditary hemochromatosis (HH) is an important genetic risk factor for HCC. HH is an autosomal recessive disorder of iron metabolism, characterised by elevated iron deposition in most organs including the liver, leading to progressive organ dysfunction. HCC is a complication of HH, nearly always occurring in patients with cirrhosis and contributes to increased mortality rates. Identifying the susceptibility of development of HCC in HH patients has gained much traction. This review summarises the current knowledge with regard to the association of HH and HCC in order to encourage further research. In this review, we focus particularly on HFE gene-related HH. Herein, we highlight and discuss emerging clinical research which addresses the prevalence of HCC in HH patients and the coincidence of HH with other risk factors for HCC development. We also focus on the therapeutic tools in the management of HCC associated with HH.

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Section: Mechanisms Of Iron Toxicity In Hh Leading To Hccmentioning

confidence: 72%

Section: Mechanisms Of Iron Toxicity In Hh Leading To Hccmentioning

confidence: 99%

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Jayachandran¹,

Shrestha²,

Bridle³

et al. 2020

View full text Add to dashboard Cite

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“…Disordered iron metabolism is one of the hallmarks of malignancies, in which iron is required for the growth, metastasis and survival of tumor cells (19,20). Previous studies have shown that iron plays a signi cant role in the development of HCC (21). HCC requires excess iron to meet the demands of rapid proliferation and DNA duplication (22).…”

Section: Discussionmentioning

confidence: 99%

“…Iron metabolism is associated with the prognosis of cancer patients, including HCC patients (21). Therefore, we performed Cox regression analysis and LASSO regression analysis to construct a nine-gene prognostic signature with iron metabolism-related genes, which consists of FBXL5, SLC48A1, BMP6, HAVCR1, ALAS1, CD163, PCBP2, FLVCR1 and ABCB6.…”

Section: Discussionmentioning

confidence: 99%

Identification of Iron Metabolism-Related Genes Signature and Novel Role of FLVCR1 in Hepatocellular Carcinoma

Chen¹,

Hu²,

Pan³

et al. 2020

Preprint

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Background: Hepatocellular carcinoma (HCC) is the main and highly malignant histological subtype of liver cancer. We tried to construct a novel signature with iron metabolism-related genes to provide new therapeutic targets and improve the prognosis for HCC patients.Methods: The gene expression data of 70 iron metabolism-related genes and its relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Consensus clustering analysis was performed to determine clusters of HCC patients with different OS. Cox regression and LASSO regression analyses were used to establish a prognostic signature. Receiver operating characteristic (ROC) and Kaplan–Meier analyses were carried out to examine the predicated performance of the signature.Results: Consensus clustering analysis determined two clusters of HCC patients with different OS(p<0.01), TNM stage(p<0.05) and pathological grade(p<0.05). A nine-gene prognostic signature established with iron metabolism-related genes can independently predicate the prognostic of HCC patients. The ROC curves showed a great performance of the signature. In addition, FLVCR1, a hub gene with the highest mutation frequency in our signature, showed the significantly prognostic value in HCC patients. High FLVCR1 expression was significantly associated with poor prognosis and aggressive progression in HCC patients. The promoter methylation level of FLVCR1 was lower in HCC samples with aggressive progression status. The FLVCR1 expression was positively correlated with the infiltration level of B cell, CD4+ T cell, macrophage, neutrophil and dendritic cell. Conclusion: Our study first established a signature related to iron metabolism and identified FLVCR1 as a potential therapeutic target. These findings provided more treatment strategies for HCC patients.

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“…Clinical analysis found that FLVCR1 was signi cantly negatively correlated with maternal iron levels and placental iron concentration, suggesting that FLVCR1 is essential for iron homeostasis and iron metabolism [55]. Studies also found that FLVCR1 expression is correlated with the prognosis of HCC [56]. SLC48A1 is an endosomal heme transporter that participates in the process of heme iron transport in iron metabolism [57].…”

Section: Discussionmentioning

confidence: 99%

The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

Tang

Zhu

et al. 2020

Preprint

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Background : In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC. Methods : Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes. Results : four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy. Conclusions: The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients.

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Iron metabolism gene expression and prognostic features of hepatocellular carcinoma

Cited by 65 publications

References 53 publications

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Association between hereditary hemochromatosis and hepatocellular carcinoma: a comprehensive review

Identification of Iron Metabolism-Related Genes Signature and Novel Role of FLVCR1 in Hepatocellular Carcinoma

The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma

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