Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Severi, Tamara; Malenstein, Hannah van; Verslype, Chris; Pelt, Jos van

doi:10.1038/aps.2010.142

Cited by 156 publications

(136 citation statements)

References 125 publications

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“…The highest liver cancer rates are observed in developing countries, particularly in East Asia and Malaysia, South Africa and Sub-Saharan Africa, whereas rates are lower in Europe, North and South America, Australia and New Zealand (3). HCC may be induced by a number of risk factors, including chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), hepatic cirrhosis, alcoholic liver disease and exposure to aflatoxins (4).…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Jianzhi

et al. 2016

Oncology Letters

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Abstract. The present study aimed to investigate the expression level of HOX transcript antisense RNA (HOTAIR) in hepatocellular carcinoma (HCC) and its association with various clinicopathological characteristics, and to further explore the molecular mechanisms of HOTAIR function in HCC. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of HOTAIR in 60 paired fresh HCC samples and adjacent normal liver tissue samples. The association between HOTAIR expression and clinicopathological parameters was analyzed. Lentivirus-mediated HOTAIR-specific small hairpin RNA vectors were transfected into HepG2 cells. Cell proliferation and invasion in vitro were examined by MTT and Transwell assays, respectively. A xenograft model was used to analyze the tumorigenesis of liver cancer cells in vivo. In addition, semi-quantitative RT-PCR was used to detect the expression level of Wnt/β-catenin signaling molecules under the condition of HOTAIR inhibition. The results revealed that the expression level of HOTAIR in HCC tissues was higher than that in adjacent non-cancerous tissues. HOTAIR expression was significantly associated with poor tumor differentiation (P=0.002), metastasis (P=0.002) and early recurrence (P=0.001). In vitro, the inhibition of HOTAIR in liver cancer cells resulted in the suppression of cell proliferation and invasion. HOTAIR depletion significantly inhibited the rate of growth of liver cancer cells in vivo. Furthermore, the expression levels of Wnt and β-catenin were downregulated when HOTAIR expression was suppressed. In conclusion, HOTAIR is important in the progression and recurrence of HCC, partly through the regulation of the Wnt/β-catenin signaling pathway. Targeting HOTAIR may be a novel therapeutic strategy for HCC.

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Section: Introductionmentioning

confidence: 99%

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Jianzhi

et al. 2016

Oncology Letters

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“…Hypoxia is a major cause of hypervasculature of HCC by inducing angiogenic factors to stimulate angiogenesis and support tumor growth [15] . In addition, a variety of genes would be transactivated under hypoxia by HIFs or the other transcriptional factor and involved in multiple steps of HCC metastasis including epithelial-mesenchymal transition (EMT), invasion of the extracellular matrix, intravasation, extravasation, and secondary growth of the metastases [5] . Besides, hypoxia-regulated glycolysis module also contributes to HCC progression [16] .…”

Section: Hypoxia Plays Critical Roles In the Progression And Malignanmentioning

confidence: 99%

“…There are various etiologies implicated in development of HCC, including infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) [3,4] , chronic infection, and alcohol consumption [5] . According to the Barcelona Clinic Liver Cancer (BCLC) staging, HCCs can be classified into five stages with each receiving different treatments [1] .…”

Section: Introductionmentioning

confidence: 99%

Hypoxic microenvironment and hepatocellular carcinoma treatment

Lin¹,

Chang²,

Zhu³

et al. 2018

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Hepatocellular carcinoma (HCC) is one of the most rapidly growing and prevalent cancers in the whole world. The characterized hypoxia region inside the HCC tumors has been recently found as the key driver of HCC malignance and treatment failure, leading to a variety of hypoxia-related biological consequences including angiogenesis, metastasis, metabolism deregulation and drug resistance, which ultimately resulted in treatment failure of HCC. This review will summarize the signaling pathways involved in hypoxia-mediated malignance of HCC and discuss current advances of hypoxia-targeted therapies.

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“…From these studies, circulating reactive oxygen species (ROS), which are produced by host inflammatory cells upon stimulation by bacterial pathogens (24), were identified as a fundamental attributable factor to the association between HCC metastasis and chronic periodontitis. Furthermore, Severi et al identified that ROS were involved in the transcriptional activation of a large series of cytokines and growth factors that ultimately lead to malignant transformation (25). The results indicated that periodontitis may affect HCC by increasing the number of circulating ROS.…”

Section: A B C Dmentioning

confidence: 99%

Hepatocellular carcinoma metastasis to the gingival soft tissues: A case report and review of the literature

Gong

Zhang

et al. 2015

Oncology Letters

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Abstract. Metastases to the gingival soft tissues are rare in hepatocellular carcinoma (HCC). To the best of our knowledge, only 13 cases have been reported in English literature to date. The present study described the case of a 43-year-old Chinese man who was admitted to Tangdu Hospital (Xi'an, China) due to the presence of a gingival tumor that was initially diagnosed as granulation tissue by a dental surgeon. Examination of the patient's medical history revealed that a solid mass, measuring 1.5 cm in diameter, was identified in the right lobe of the liver 2 years prior to presentation at the current hospital; however, no biopsy was performed. Thus, the tumor was resected and histological examination resulted in an initial diagnosis of atypical squamous cell carcinoma. However, the histopathological characteristics, immunohistochemical features and serum α-fetoprotein expression levels supported a diagnosis of metastatic HCC. In conclusion, the present case study highlights the difficulties in diagnosing metastatic HCC without a history of primary HCC, and the importance of excluding a diagnosis of metastatic tumor when a lesion is identified in the gingival. Furthermore, it was determined that a final diagnosis of gingival metastasis of HCC predominantly depends on pathological characteristics and immunohistochemical features.

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Tumor initiation and progression in hepatocellular carcinoma: risk factors, classification, and therapeutic targets

Cited by 156 publications

References 125 publications

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Long non-coding RNA HOTAIR is a marker for hepatocellular carcinoma progression and tumor recurrence

Hypoxic microenvironment and hepatocellular carcinoma treatment

Hepatocellular carcinoma metastasis to the gingival soft tissues: A case report and review of the literature

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