《医学前沿（英文）》 2016年 第10卷 第2期 页码 183-190 doi: 10.1007/s11684-016-0440-4
We performed weighted gene coexpression network analysis (WGCNA) to gain insights into the molecular aspects of hepatocellular carcinoma (HCC). Raw microarray datasets (including 488 samples) were downloaded from the Gene Expression Omnibus (GEO) website. Data were normalized using the RMA algorithm. We utilized the WGCNA to identify the coexpressed genes (modules) after non-specific filtering. Correlation and survival analyses were conducted using the modules, and gene ontology (GO) enrichment was applied to explore the possible mechanisms. Eight distinct modules were identified by the WGCNA. Pink and red modules were associated with liver function, whereas turquoise and black modules were inversely correlated with tumor staging. Poor outcomes were found in the low expression group in the turquoise module and in the high expression group in the red module. In addition, GO enrichment analysis suggested that inflammation, immune, virus-related, and interferon-mediated pathways were enriched in the turquoise module. Several potential biomarkers, such as cyclin-dependent kinase 1 (CDK1), topoisomerase 2α (TOP2A), and serpin peptidase inhibitor clade C (antithrombin) member 1 (SERPINC1), were also identified. In conclusion, gene signatures identified from the genome-based assays could contribute to HCC stratification. WGCNA was able to identify significant groups of genes associated with cancer prognosis.
《医学前沿（英文）》 2014年 第8卷 第1期 页码 33-41 doi: 10.1007/s11684-013-0301-3
Hypoxia is a common phenomenon in hepatocellular carcinoma (HCC). Hypoxia stabilizes transcription factor, hypoxia-inducible factor (HIF), to activate gene transcription. Expression of HIF is closely associated with metastasis and poor prognosis in HCC. HIF mediates expression of genes that are involved in every step of HCC metastasis including epithelial-mesenchymal transition, invasion of the extracellular matrix, intravasation, extravasation, and secondar y growth of the metastases. Because HIF is the central regulator of HCC metastasis, HIF inhibitors are attractive tools when used alone or as combined treatment to curb HCC metastasis. This review will summarize the current findings on the impact of hypoxia/HIF in HCC, with a particular focus on cancer metastasis.
Amy Lee, Fa-Chyi Lee
《医学前沿（英文）》 2020年 第14卷 第3期 页码 273-283 doi: 10.1007/s11684-019-0728-2
《医学前沿（英文）》 2017年 第11卷 第4期 页码 509-521 doi: 10.1007/s11684-017-0546-3
Hepatocellular carcinoma (HCC) is currently the fifth most common malignancy and the third leading cause of cancer-related mortalities worldwide. In the last few years, treatments for HCC have significantly improved from a mere surgical resection to a series of minimally invasive therapies and targeted drugs. However, recurrence frequently occurs even upon curative therapeutics, and drug therapies generally produce disappointing results, with the overall prognosis dismal. This challenging clinical scenario warrants new effective and life-prolonging strategies for patients with HCC. Compelling evidence suggests that NK cells play a critical role in the immune function of the liver and in the immune defenses against HCC, indicating that HCC might be an ideal target for NK cell-based immunotherapies. To obtain comprehensive insights into the putative influence of NK cells on HCC, this paper summarizes current knowledge on NK cells in HCC and discusses the usefulness and prospects of NK cell-based immunotherapies. Critical issues that require consideration for the successful clinical translation of NK cell-based therapies are also addressed. If appropriately used and further optimized, NK cell-based therapies could dominate important roles in the future immunotherapeutic market of HCC.
《医学前沿（英文）》 2014年 第8卷 第1期 页码 24-32 doi: 10.1007/s11684-014-0312-8
In this review, we summarize the novel findings from our series of studies on the leading metastasis-related gene, osteopontin (OPN). In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma (HCC). We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivoinvestigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPN+ HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.
《医学前沿（英文）》 2014年 第8卷 第2期 页码 175-189 doi: 10.1007/s11684-014-0332-4
Multiple modalities for treatment of hepatocellular carcinoma are available, depending on tumor size and number. Surgical resection remains the gold standard, so long as the residual liver function reserve is sufficient. In patients with advanced cirrhosis, liver transplantation is the preferred option, as these patients may not have adequate hepatic reserve after resection. Salvage liver transplantation has also become an option for a select few patients who recur after surgical resection. Ablative techniques have been used for palliation as well as to either completely destroy the tumor, act as an adjunct to resection, or downstage the tumor to meet Milan criteria such that a patient may be a candidate for liver transplantation. Radiofrequency ablation, microwave ablation, chemoembolization, radioembolization, and irreversible electroporation have all been used in this capacity. Currently, sorafenib is the only US Food and Drug Administration-approved chemotherapeutic for hepatocellular carcinoma. The efficacy of sorafenib, in combination with other agents, transarterial chemoembolization, and surgical resection is currently being investigated. Sunitinib and brivanib, tyrosine kinase inhibitors, have failed as potential first- or second-line options for chemotherapy. Bevacizumab in combination with erlotinib is also currently being studied. Final analysis for ramucirumab and axitinib are pending. Tivantinib, a selective mesenchymal-epithelial transition factor (MET) inhibitor, is also undergoing clinical trials for efficacy in MET-high tumors. This review serves to emphasize the current and new technologies emerging in the treatment of hepatocellular carcinoma.
Jianpeng Liu, Xinhua Chen, Shusen Zheng
《医学前沿（英文）》 2021年 第15卷 第2期 页码 170-177 doi: 10.1007/s11684-020-0747-z
《医学前沿（英文）》 2022年 第16卷 第3期 页码 467-482 doi: 10.1007/s11684-021-0869-y
《医学前沿（英文）》 2012年 第6卷 第2期 页码 122-133 doi: 10.1007/s11684-012-0193-7
Hepatocellular carcinoma (HCC) is a highly complex disease that is generally resistant to commonly used chemotherapy and radiotherapy. Consequently, there is an urgent need for the development of new treatment strategies for this devastating disease. In the past decade, tremendous progress has been achieved in the molecular stratification of HCCs for diagnosis, prognosis, and therapeutic decision-making. To date, the molecular classification of HCCs has been carried out through transcriptomic, genetic and epigenetic profiling of tumors. Such research has led to identification of several potential molecular targets in HCC, and subsequently, development of novel systemic agents for the treatment of HCC has begun in earnest. In this article, we review the current knowledge of the molecular pathogenesis of HCC and outline potential areas for application of this knowledge in a clinical setting. As a typical virus and inflammation-associated cancer, both host immune response and tumor microenvironment have crucial roles in HCC pathogenesis. In addition, we examine the potential of immunotherapy and strategies targeting various components of the tumor microenvironment, as well as novel molecular and cellular targets in HCC such as cancer stem cells.
《医学前沿（英文）》 2015年 第9卷 第1期 页码 63-71 doi: 10.1007/s11684-014-0342-2
Cryoablation is a less prevalent percutaneous ablative therapy for hepatocellular carcinoma (HCC), and current evidence about its usefulness is limited. We report our experience in treating 1595 HCC cases with percutaneous cryoablation to give a comprehensive profile about the effectiveness, safety and long-term outcome of this therapy. From January 2003 to December 2013, 1595 patients with 2313 HCC nodules were ablated with 2945 cryoablation sessions in our center. Complete ablation was achieved in 1294 patients for 1893 nodules with a mean diameter of 3.4±2.2 cm. The complete ablation rate was 81.2%, 99.4%, 94.4%, and 45.6% in all tumors, tumors<3 cm, tumors<5 cm, and tumors>5 cm, respectively. Major complications were observed after 80 (3.4%) of the 2945 cryoablations and minor complications were observed after 330 cryoablations with no treatment-related deaths. After a median follow-up of 33.4 months, 937 patients developed different types of recurrence. The 5- and 10-year overall survival was 25.7% and 9.2%, respectively. Cryoablation showed reliable safety and efficacy and should be considered as a promising technique, particularly when a large zone of ablation is required.
《医学前沿（英文）》 页码 729-746 doi: 10.1007/s11684-022-0978-2
《医学前沿（英文）》 2022年 第16卷 第4期 页码 551-573 doi: 10.1007/s11684-022-0928-z
《医学前沿（英文）》 2014年 第8卷 第2期 页码 217-226 doi: 10.1007/s11684-014-0326-2
This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.
《医学前沿（英文）》 2023年 第17卷 第3期 页码 476-492 doi: 10.1007/s11684-022-0966-6
《医学前沿（英文）》 2015年 第9卷 第3期 页码 331-343 doi: 10.1007/s11684-015-0409-8
MicroRNAs (miRNAs), an important class of small non-coding RNAs, regulate gene expression at the post-transcriptional level. miRNAs are involved in a wide range of biological processes and implicated in different diseases, including cancers. In this study, miRNA profiling and qRT-PCR validation revealed that miR-142-3p and miR-142-5p were significantly downregulated in hepatocellular carcinoma (HCC) and their expression levels decreased as the disease progressed. The ectopic expression of miR-142 significantly reduced HCC cell migration and invasion. Overexpression of either miR-142-3p or miR-142-5p suppressed HCC cell migration, and overexpression of both synergistically inhibited cell migration, which indicated that miR-142-3p and miR-142-5p may cooperatively regulate cell movement. miR-142-3p and miR-142-5p, which are mature miRNAs derived from the 3′- and 5′-strands of the precursor miR-142, target distinct pools of genes because of their different seed sequences. Pathway enrichment analysis showed a strong association of the putative gene targets of miR-142-3p and miR-142-5p with several cell motility-associated pathways, including those regulating actin cytoskeleton, adherens junctions, and focal adhesion. Importantly, a number of the putative gene targets were also significantly upregulated in human HCC cells. Moreover, overexpression of miR-142 significantly abrogated stress fiber formation in HCC cells and led to cell shrinkage. This study shows that mature miR-142 pairs collaboratively regulate different components of distinct signaling cascades and therefore affects the motility of HCC cells.
标题 作者 时间 类型 操作
Transcriptional modules related to hepatocellular carcinoma survival: coexpression network analysis
Medical oncology management of advanced hepatocellular carcinoma 2019: a reality check
Amy Lee, Fa-Chyi Lee
Natural killer cells in hepatocellular carcinoma: current status and perspectives for future immunotherapeutic
Osteopontin is a promoter for hepatocellular carcinoma metastasis: a summary of 10 years of studies
Immune response triggered by the ablation of hepatocellular carcinoma with nanosecond pulsed electric
Jianpeng Liu, Xinhua Chen, Shusen Zheng
Rapamycin enhances the anti-tumor activity of cabozantinib in cMet inhibitor-resistant hepatocellularcarcinoma
Cryotherapy for cirrhosis-based hepatocellular carcinoma: a single center experience from 1595 treated
Dihydroartemisinin increased the abundance of by YAP1 depression that sensitizes hepatocellular carcinoma
Bone metastasis of hepatocellular carcinoma: facts and hopes from clinical and translational perspectives
polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations with hepatocellularcarcinoma risk
5′-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction