Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Guan, Ming-Cheng; Wang, Mingda; Liu, Siyu; Ouyang, Wei; Liang, Lei; Pawlik, Timothy M.; Xu, Qiuran; Huang, Dongsheng; Shen, Feng; Zhu, Hong

doi:10.4251/wjgo.v13.i4.197

Cited by 22 publications

(12 citation statements)

References 119 publications

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“…Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the third most common cause of cancer death [ 1 ]. The current conventional treatment method is still surgical resection; the drug treatment method is still unsatisfactory; and the side effects of the currently used drugs are relatively large [ 2 ]. With the development of research, natural products and their structural analogs have made significant contributions to the drug treatment of cancer and are expected to provide a new path for drug treatment of cancer [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

Huang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Objective. Hedyotis diffusa Willd. (HDW) is a famous Chinese herbal medicine, traditionally used to treat cancer in China. Currently, the clinically used drugs for the treatment of hepatocellular carcinoma (HCC) still have poor efficacy and have many side effects. HDW has fewer side effects after taking it, so this study explores the inhibitory effect of HDW on HCC, which may become a promising drug for the treatment of HCC. Methods. HCC cell lines such as SMMC-7721, SK-hep1, and Hep-G2 were treated with Hedyotis diffusa Willd. (HDW), after which migration was detected via transwell, while the proliferation of these cells was detected via MTT, CCK-8, and colony formation assays. Furthermore, protein levels were evaluated by western blotting, and Hep-G2 cells were implanted in nude mice to establish a xenograft model to evaluate the antitumor effect of the drug. Results. HDW exhibited the ability to inhibit the proliferation and migration of HCC cells. And its anticancer mechanism in hepatocellular carcinoma may be via AKT/mTOR pathway. Moreover, the drug use of HDW in the mouse model system has achieved a good effect. Importantly, it did not cause significant weight loss or hepatorenal toxicity. Conclusion. HDW can suppress the activation of the AKT/mTOR pathway in HCC cells, which may bring new light for the treatment of this kind of malignant tumor, but its exact mechanism still needs to be further explored.

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Section: Introductionmentioning

confidence: 99%

Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

Huang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…More importantly, several validated HCC-driver genes, such as YY1AP1 and ECT2, were highly expressed in HPC-like cells and markedly correlated with CEP192 expression in HCC tissues (Figure 4E). Subsequently, the HPC-like cells were classified into 12 subpopulations (Figure 4F), and CEP192 was expressed in HPC (6), HPC (7), and HPC (8) (Figure 4G). Next, GO enrichment analysis of HPC(6)-specific genes revealed a series of cellular responses to wounding, wound healing, toxic substance, and endoplasmic reticulum stress (Figure 4H).…”

Section: Cep192 Was Associated With Hepatic Progenitor Cell-driven Im...mentioning

confidence: 99%

“…Next, GO enrichment analysis of HPC(6)-specific genes revealed a series of cellular responses to wounding, wound healing, toxic substance, and endoplasmic reticulum stress (Figure 4H). Moreover, HPC (6) weakly expressed the hepatocyte-specific gene ALB; therefore, HPC (6) may be hepatocyte precursor cells. Moreover, HPC (7) expressed relatively high levels of CEP192, VEGFA (vascular endothelial growth factor A, the central angiogenic cytokine), and the fetal-like gene CD24 (Figure 4G).…”

Section: Cep192 Was Associated With Hepatic Progenitor Cell-driven Im...mentioning

confidence: 99%

“…Surveillance using abdominal ultrasonography and serum alpha-fetoprotein (AFP) was recommended in high-risk populations to detect HCC early for potentially curative surgical resection or transplantation ( 6 ). However, the accuracy of surveillance is relatively low (40%–50%), and approximately half of the patients are diagnosed with advanced stages when systemic therapy remains the only standard treatment option.…”

Section: Introductionmentioning

confidence: 99%

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CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

Liang

Chang

et al. 2022

Front. Immunol.

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Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

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“…Despite the advances in therapy, patients with HCC still have poor outcome, especially those at advanced stages [ 2 ]. Therefore, early diagnosis and risk stratification of prognosis are of great significance for patients with liver cancer, and initiating effective treatment expeditiously may efficiently improve their prognosis [ 3 ]. Unfortunately, real-world utilization of biomarkers to predict clinical outcome of HCC patients by precise classification and specific clinical decision-making remains urgent but still lacking.…”

Section: Introductionmentioning

confidence: 99%

Deep View of HCC Gene Expression Signatures and Their Comparison with Other Cancers

Qian

Itzel

Ebert

et al. 2022

Cancers

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Background: Gene expression signatures correlate genetic alterations with specific clinical features, providing the potential for clinical usage. A plethora of HCC-dependent gene signatures have been developed in the last two decades. However, none of them has made its way into clinical practice. Thus, we investigated the specificity of public gene signatures to HCC by establishing a comparative transcriptomic analysis, as this may be essential for clinical applications. Methods: We collected 10 public HCC gene signatures and evaluated them by utilizing four different (commercial and non-commercial) gene expression profile comparison tools: Oncomine Premium, SigCom LINCS, ProfileChaser (modified version), and GENEVA, which can assign similar pre-analyzed profiles of patients with tumors or cancer cell lines to our gene signatures of interests. Among the query results of each tool, different cancer entities were screened. In addition, seven breast and colorectal cancer gene signatures were included in order to further challenge tumor specificity of gene expression signatures. Results: Although the specificity of the evaluated HCC gene signatures varied considerably, none of the gene signatures showed strict specificity to HCC. All gene signatures exhibited potential significant specificity to other cancers, particularly for colorectal and breast cancer. Since signature specificity proved challenging, we furthermore investigated common core genes and overlapping enriched pathways among all gene signatures, which, however, showed no or only very little overlap, respectively. Conclusion: Our study demonstrates that specificity, independent validation, and clinical use of HCC genetic signatures solely relying on gene expression remains challenging. Furthermore, our work made clear that standards in signature generation and statistical methods but potentially also in tissue preparation are urgently needed.

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Early diagnosis and therapeutic strategies for hepatocellular carcinoma: From bench to bedside

Cited by 22 publications

References 119 publications

Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways

CEP192 is a novel prognostic marker and correlates with the immune microenvironment in hepatocellular carcinoma

Deep View of HCC Gene Expression Signatures and Their Comparison with Other Cancers

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