Intratumor heterogeneity in HCC

Friemel, Juliane; Frick, Lukas; Weber, Achim

doi:10.18632/aging.100760

Cited by 9 publications

(7 citation statements)

References 7 publications

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“…Hepatocellular carcinoma, one of the malignant cancers with high heterogeneity, is frequently diagnosed in its middle and advanced stages ( Friemel et al, 2015 ; Buczak et al, 2018 ). Surgical resection remains the most crucial technique for HCC treatment; however, its therapeutic effects are always unsatisfactory ( Abe et al, 2017 ; Deng et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes Associated With Immune Infiltration and Predict Prognosis in Hepatocellular Carcinoma via Bioinformatics Approaches

Chen

et al. 2021

Front. Genet.

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AimsIn the cancer-related research field, there is currently a major need for a greater number of valuable biomarkers to predict the prognosis of hepatocellular carcinoma (HCC). In this study, we aimed to screen hub genes related to immune cell infiltration and explore their prognostic value for HCC.MethodsWe analyzed five datasets (GSE46408, GSE57957, GSE74656, GSE76427, and GSE87630) from the Gene Expression Omnibus database to screen the differentially expressed genes (DEGs). A protein–protein interaction network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes; then, the hub genes were identified. Functional enrichment of the genes was performed on the Metascape website. Next, the expression of these hub genes was validated in several databases, including Oncomine, Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and Human Protein Atlas. We explored the correlations between the hub genes and infiltrated immune cells in the TIMER2.0 database. The survival curves were generated in GEPIA2, and the univariate and multivariate Cox regression analyses were performed using TIMER2.0.ResultsThe top ten hub genes [DNA topoisomerase II alpha (TOP2A), cyclin B2 (CCNB2), protein regulator of cytokinesis 1 (PRC1), Rac GTPase-activating protein 1 (RACGAP1), aurora kinase A (AURKA), cyclin-dependent kinase inhibitor 3 (CDKN3), nucleolar and spindle-associated protein 1 (NUSAP1), cell division cycle-associated 5 (CDCA5), abnormal spindle microtubule assembly (ASPM), and non-SMC condensin I complex subunit G (NCAPG)] were identified in subsequent analysis. These genes are most markedly enriched in cell division, suggesting their close association with tumorigenesis. Multi-database analyses validated that the hub genes were upregulated in HCC tissues. All hub genes positively correlated with several types of immune infiltration, including B cells, CD4+ T cells, macrophages, and dendritic cells. Furthermore, these hub genes served as independent prognostic factors, and the expression of these hub genes combing with the macrophage levels could help predict an unfavorable prognosis of HCC.ConclusionIn sum, these hub genes (TOP2A, CCNB2, PRC1, RACGAP1, AURKA, CDKN3, NUSAP1, CDCA5, ASPM, and NCAPG) may be pivotal markers for prognostic prediction as well as potentially work as targets for immune-based intervention strategies in HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of Hub Genes Associated With Immune Infiltration and Predict Prognosis in Hepatocellular Carcinoma via Bioinformatics Approaches

Chen

et al. 2021

Front. Genet.

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“…Resistant subpopulations which are often poorly differentiated tend to escape from chemotherapies and overgrow due to a forced selection in exposure to chemotherapy. 6 Our preliminary RNA-sequencing (RNA-Seq) study revealed that another ABC member, TAP1 (ABCB2, ABC subfamily B member) highly expressed in both Huh-7-trans and Huh-7-DN subpopulations.…”

Section: Introductionmentioning

confidence: 98%

Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma

Zhou

Ding

et al. 2020

J Cellular Molecular Medi

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Multidrug resistance is one of the reasons for low survival of advanced hepatocellular carcinoma (HCC). Our previous studies indicate that the hedgehog signalling is involved in hepatic carcinogenesis, metastasis and chemo-resistance. The present study aims to uncover molecular mechanisms underlying hepatoma chemo-resistance. TAP1 and GLI1/2 gene expression was assessed in both poorly differentiated hepatoma cells and HCC specimens. Potential GLI-binding site in the TAP1 promoter sequence was validated by molecular assays. Approximately 75% HCC specimens exhibited an elevated expression of hedgehog GLI1 transcription factor compared with adjacent liver tissue. Both GLI1/2 and TAP1 protein levels were significantly elevated in poorly differentiated hepatoma cells. Both Huh-7-trans and Huh-7-DN displayed more karyotypic abnormalities and differential gene expression profiles than their native Huh-7 cells. Sensitivity to Sorafenib, doxorubicin and cisplatin was remarkably improved after either GLI1 or TAP1 gene was inhibited by an RNAi approach or by a specific GLI1/2 inhibitor, GANT61. Further experiments confirmed that hedgehog transcription factor GLI1/2 binds to the TAP1 promoter, indicating that TAP1 is one of GLI1/2 target genes. In conclusion, TAP1 is under direct transcriptional control of the hedgehog signalling. Targeting hedgehog signalling confers a novel insight into alleviating drug resistance in the treatment of refractory HCC. K E Y W O R D Schemo-resistance, GANT61, hedgehog signalling, hepatocellular carcinoma, TAP1 | 4299 ZHOU et al.

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“…Liver cancer is listed as the fourth common malignancy and the second major cause of death 1,2 . Treatment strategies for liver cancer are limited, especially for the patients with distant metastasis and recurrence after surgery 3,4 .…”

Section: Introductionmentioning

confidence: 99%

Circ_0000105 promotes liver cancer by regulating miR‐498/PIK3R1

Sun

Huang

2020

The Journal of Gene Medicine

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Background: A growing number of studies demonstrate that circular RNA (circRNA) has a prominent role in the regulation of numerous biological behaviors of tumor cells. The present study aimed to investigate the expression, function and molecular mechanisms of circ_0000105 in liver cancer. Methods: A quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to obtain the expressions of circ_0000105 and miR-498 in liver cancer tissues and cells. The association between the expression level of circ_0000105 and the clinicopathological characteristics of liver cancer patients was analyzed. qRT-PCR and western blotting were utilized to investigate the expression of phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) in cells. Cell counting kit-8, bromodeoxyuridine and flow cytometry assays were utilized to determine liver cancer cell proliferation and apoptosis, respectively. Bioinformatics, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were conducted to predict and confirm the targeting correlation of circ_0000105 and miR-498, as well as miR-498 and PIK3R1. Results: Circ_0000105 was highly expressed in liver cancer tissues and cell lines. Moreover, its high expression was associated with an increase in the T stage of liver cancer patients and a low degree of tumor differentiation. Circ_0000105 overexpression promoted liver cancer cell proliferation and inhibited apoptosis, whereas knocking down circ_0000105 triggered the opposite effect. miR-498 was a downstream target of circ_0000105, inhibiting liver cancer cell proliferation and promoting apoptosis. Mechanistically, circ_0000105 indirectly up-regulated the expression of PIK3R1 by adsorbing miR-498. Conclusions: Circ_0000105 plays a cancer-promoting role in liver cancer by regulating the miR-498/PIK3R1 axis.

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Intratumor heterogeneity in HCC

Cited by 9 publications

References 7 publications

Identification of Hub Genes Associated With Immune Infiltration and Predict Prognosis in Hepatocellular Carcinoma via Bioinformatics Approaches

Identification of Hub Genes Associated With Immune Infiltration and Predict Prognosis in Hepatocellular Carcinoma via Bioinformatics Approaches

Hedgehog signalling mediates drug resistance through targeting TAP1 in hepatocellular carcinoma

Circ_0000105 promotes liver cancer by regulating miR‐498/PIK3R1

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