• ARID2
• Sarcomatoid hepatocellular carcinoma
• Therapeutic strategies

• 82372985 National Natural Science Foundation of China
• 82373418 National Natural Science Foundation of China
• 82273247, 82173260 National Natural Science Foundation of China
• 82072681, 82003082 National Natural Science Foundation of China
• 22Y11907300 Shanghai Medical Innovation Research Project

• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Molecular targeted therapy
• Mutation, tumor microenvironment

• 24K10393 Japan Society for the Promotion of Science

• Liver Neoplasms/immunology
• Liver Neoplasms/therapy
• Epitopes, T-Lymphocyte/immunology
• Immunotherapy/methods
• Humans
• Molecular Dynamics Simulation
• Cancer Vaccines/immunology
• Machine Learning
• Antigens, Neoplasm/immunology
• CD8-Positive T-Lymphocytes/immunology

• LIFR
• hepatocellular carcinoma
• histone acetylation
• hsa_circ_007230

• Humans
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Liver Neoplasms/metabolism
• RNA, Circular/genetics
• RNA, Circular/metabolism
• Epigenesis, Genetic
• Cell Line, Tumor
• Cell Proliferation
• Leukemia Inhibitory Factor Receptor alpha Subunit/genetics
• Leukemia Inhibitory Factor Receptor alpha Subunit/metabolism
• Carcinogenesis/genetics
• Cell Movement
• Sorafenib/pharmacology
• RNA/metabolism
• RNA/genetics
• E1A-Associated p300 Protein/metabolism
• E1A-Associated p300 Protein/genetics
• Gene Expression Regulation, Neoplastic
• Drug Resistance, Neoplasm/genetics
• Histones/metabolism

• Humans
• Male
• Female
• Middle Aged
• Lymphoma/drug therapy
• Neoplasms/drug therapy
• Aged
• Adult
• China
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antibodies, Monoclonal, Humanized/pharmacology
• Maximum Tolerated Dose
• East Asian People

• HIF-1α
• hepatocellular carcinoma
• noncoding RNAs
• tumor microenvironment

• Humans
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Tumor Microenvironment/genetics
• MicroRNAs/genetics
• Biomarkers
• RNA, Long Noncoding/genetics
• Hypoxia
• Carcinogenesis
• Hypoxia-Inducible Factor 1, alpha Subunit
• Gene Expression Regulation, Neoplastic

• Autophagy
• Hepatocellular carcinoma
• Immune escape
• Mitochondria
• Mitokine

• CircDLG1
• Hepatocellular carcinoma
• WTAP
• miR-141-3p

• Humans
• Carcinogenesis/genetics
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation/genetics
• Gene Expression Regulation, Neoplastic
• In Situ Hybridization, Fluorescence
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• MicroRNAs/genetics
• MicroRNAs/metabolism
• RNA Splicing Factors/genetics
• RNA Splicing Factors/metabolism
• RNA, Circular/genetics

• LHGJ20190658 Henan Province Medical Science and Technology Tackling Program (Jointly Co-construction) Project

• Combination therapy
• Hepatocellular carcinoma (HCC)
• Immune checkpoint inhibitors (ICIs)
• Immunotherapy
• Programmed cell death protein 1 (PD-1)

• HBV
• LIHC
• immune microenvironment
• molecular subtypes
• prognostic characteristics

Liver hepatocellular carcinoma (LIHC) is among the most frequent causes of cancer-related death across the world with a considerably poor prognosis. The current study targeted providing a new type of LIHC from the perspective of the glycolysis/cholesterol synthesis axis, predicting its prognostic characteristics, and exploring the potential role and mechanism of the glycolysis/cholesterol synthesis axis in the occurrence and development of LIHC.

Based on the two expression profile data and clinical information of LIHC in The Cancer Genome Atlas (TCGA) database and hepatocellular carcinoma database (HCCDB), as well as glycolysis/cholesterol-related genes from the Molecular Signatures Database (MSigDB), unsupervised consistent clustering method was used to identify molecular subtypes. In addition, the differential genes were identified by limma package, and then the gene set was enriched, analyzed, and annotated by WebGestaltR package. At the same time, the immune infiltration analysis of tumor samples was carried out using the ESTIMATE to evaluate the tumor immune score of the samples. Finally, the differences in clinical characteristics among molecular subtypes were measured using univariate and multivariate Cox analyses.

According to the median standardized expression levels of glycolysis/cholesterol production genes, samples were divided into four groups (molecular subtypes): Quiescent group, Glycolysis group, Cholesterol group, and Mixed group. Significant prognostic differences were observed among the four groups. In both TCGA and HCCDB18 datasets, the prognosis of subtype Mixed was the worst, while Quiescent had a good prognosis. Cell cycle and oncogenic pathways were significantly enriched in the Mixed group. In addition, glycolysis and cholesterol production gene expressions were related to the prognostic LIHC subtype classification genes' expression levels.

Metabolic classification regarding glycolysis and cholesterol production pathways provided new insights into the biological aspects of LIHC molecular subtypes and might help to develop personalized therapies for unique tumor metabolic profiles.

A large number of cancer-related deaths in the world can be attributed to liver hepatocellular carcinoma (LIHC). The purpose of this study is to explore protein tyrosine phosphatase type IV A member 3 (PTP4A3/PRL-3) as a new and reliable biomarker to predict the prognosis of LIHC and determine the potential therapeutic targets or drugs that can be used for treating LIHC.

We included three LIHC datasets with clinical information and expression profiles from public databases. The expression level of PTP4A3 was analyzed, and based on the results, the samples were divided into high- and low-expression groups. The Kaplan–Meier survival analysis method was used to determine the relationship between PTP4A3 and prognosis. The enrichment differences among the functional pathways associated with the high- and low-expression groups were determined using the gene set enrichment analysis (GSEA) method. Five methods were used to determine the differences among the tumor microenvironment in the low- and high-expression groups. The sensitivity of the low- and high-expression groups toward different drug treatment methods was predicted by analyzing the Tumor Immune Dysfunction and Exclusion (TIDE) scores and determining the biochemical half-maximal inhibitory concentration (IC50).

The expression levels of the LIHC and adjacent samples were analyzed, and it was observed that the expression level of PTP4A3 in tumor tissue was significantly higher than the expression level of the same gene in the adjacent samples. It was also inferred that it might be a cancer-promoting gene. It was concluded that high-expression results in a significantly poor prognosis. The high-expression group was significantly enriched in the tumor-related pathways, such as the PI3K-AKT signaling pathway. In addition, the results obtained by conducting immune infiltration analysis revealed a significant positive correlation between some immune scores and the gene PTP4A3. The drug KIN001−135 and gene PTP4A3 were also found to correlate positively with each other. CP466722, Pyrimethamine, AKT inhibitor VIII, Embelin, Cisplatin, QS11, Bexarotene, and Midostaurin negatively correlated with PTP4A3 associated with the three datasets. Moreover, the drugs Cisplatin, QS11, Midostaurin, and CP466722 were more sensitive toward the high-expression group than the low PTP4A3 expression group. Significant differences were observed in these cases.

PTP4A3/PRL-3 is potentially associated with the progression, metastasis, and invasion of LIHC. The prognosis of LIHC patients is negatively impacted by the high-expression levels of the gene. The results indicate that PTP4A3/PRL-3 is an important prognostic factor for LIHC and is a new potential prognostic detection target. The discovery of the 8 drugs that were negatively associated with PTP4A3 provided a new direction that can be developed in the future for the treatment of LIHC.

• Hepatocellular carcinoma
• Prognosis predition
• RFESD
• Tumor immune microenvironment
• Tumor mutation burden
• γδ T cells

• hepatocellular carcinoma
• peripheral blood T-cell subsets
• prognosis
• systemic inflammatory response index

• Carcinoma, Hepatocellular/pathology
• Humans
• Immune Checkpoint Inhibitors
• Liver Neoplasms/pathology
• Prognosis
• Systemic Inflammatory Response Syndrome/diagnosis
• Systemic Inflammatory Response Syndrome/etiology
• Tumor Microenvironment

• hepatocellular carcinoma
• nano-delivery systems
• nanoparticles
• target therapy
• tumor microenvironment

• Cell dyshomeostasis
• Ethyl formate metabolism
• Incomplete microwave ablation (MWA)
• Nonionic MWA nanosensitizers
• Physical & chemical ablation

• Humans
• Microwaves/therapeutic use
• Neoplasm Recurrence, Local/drug therapy
• Phosphatidylinositol 3-Kinases
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Doxorubicin/pharmacology
• Doxorubicin/therapeutic use
• Treatment Outcome

• hepatocellular carcinoma
• immune cell
• psoas muscle index
• sarcopenia
• systemic inflammatory response index

• Antibody
• Antibody–drug conjugates
• CD 147
• CD 24
• Cytotoxic payload
• Glypican 3
• Hepatocellular carcinoma
• Linker
• c-Met

• Carcinoma, Hepatocellular/drug therapy
• Drug Evaluation, Preclinical
• Humans
• Immunoconjugates/therapeutic use
• Liver Neoplasms/drug therapy

• Project ID: K-PHAR-20-627 Amrita Vishwa Vidyapeetham University

Early screening and diagnosis are of great significance to the treatment and prognosis of patients with liver cancer. This study aims to explore the application value of contrast-enhanced ultrasound and enhanced CT combined with tumor markers alpha-fetoprotein (AFP) and carbohydrate antigen 199 (CA199) in the diagnosis of liver cancer.

Liver cancer group (n = 256), benign disease group (n = 110), and control group (n = 50) participated in this study. The liver cancer and benign disease groups were diagnosed pathologically by contrast-enhanced ultrasound and enhanced CT before operation. The electrochemiluminescence method was used to detect the content of AFP and CA199. And the receiver operating characteristic (ROC) curve was drawn.

The detection rate of contrast-enhanced ultrasound is higher than that of enhanced CT. Serum levels of AFP and CA199 in the liver cancer group were significantly higher than those in the benign lesion group and the control group. The ROC curve showed that the sensitivity, accuracy, and negative prediction rate of contrast-enhanced ultrasound and enhanced CT combined with tumor markers AFP and CA199 in the diagnosis of liver cancer were significantly higher than that of a single test.

The combined detection of contrast-enhanced ultrasound and enhanced CT, AFP, and CA199 significantly improved the sensitivity and accuracy of liver cancer diagnosis. It has a significant effect on the early diagnosis of liver cancer and can be used as an important means of early screening.

• Acute Kidney Injury/pathology
• Calcineurin/metabolism
• Carcinogenesis/metabolism
• Co-Repressor Proteins/metabolism
• Humans
• Immunoglobulins/metabolism
• LIM Domain Proteins/metabolism
• MicroRNAs/metabolism
• NFATC Transcription Factors/metabolism
• Neoplasms/pathology
• Nuclear Proteins/metabolism
• RNA, Antisense/metabolism
• RNA, Long Noncoding/metabolism
• Signal Transduction/physiology
• Zinc Finger Protein Gli2/metabolism

• Hepatocellular carcinoma
• Hippo signal pathway
• Interleukin-22
• Metformin
• Mst1/2
• YAP1

• Animals
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/etiology
• Disease Models, Animal
• Hippo Signaling Pathway/drug effects
• Interleukins/adverse effects
• Interleukins/metabolism
• Liver Neoplasms/drug therapy
• Liver Neoplasms/etiology
• Metformin/pharmacology
• Mice
• Interleukin-22

• 81602487 National Natural Science Foundation of China

Background: Increasing evidence supports that competing endogenous RNAs (ceRNAs) and tumor immune infiltration act as pivotal players in tumor progression of hepatocellular carcinoma (HCC). Nonetheless, comprehensive analysis focusing on ceRNAs and immune infiltration in HCC is lacking.

Methods: RNA and miRNA sequencing information, corresponding clinical annotation, and mutation data of HCC downloaded from The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) project were employed to identify significant differentially expressed mRNAs (DEMs), miRNAs (DEMis), and lncRNAs (DELs) to establish a ceRNA regulatory network. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) enrichment pathways were analyzed to functionally annotate these DEMs. A multigene-based risk signature was developed utilizing least absolute shrinkage and selection operator method (LASSO) algorithm. Moreover, survival analysis and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (TIMER, XCELL, MCPcounter, QUANTISEQ, CIBERSORT, EPIC, and CIBERSORT-ABS) were utilized to characterize tumor immune microenvironment (TIME). Finally, the mutation data were analyzed by employing “maftools” package.

Results: In total, 136 DELs, 128 DEMis, and 2,028 DEMs were recognized in HCC. A specific lncRNA–miRNA–mRNA network consisting of 3 lncRNAs, 12 miRNAs, and 21 mRNAs was established. A ceRNA-based prognostic signature was established to classify samples into two risk subgroups, which presented excellent prognostic performance. In additional, prognostic risk-clinical nomogram was delineated to assess risk of individual sample quantitatively. Besides, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was revealed.

Conclusion: In this work, comprehensive analyses of ceRNAs coexpression network will facilitate prognostic prediction, delineate complexity of TIME, and contribute insight into precision therapy for HCC.

• ceRNAs
• hepatocellular carcinoma
• immunotherapy
• prognostic prediction
• tumor immune microenvironment
• tumor mutation burden

Background: Hepatocellular carcinoma (HCC) is the sixth most common malignancy with a high mortality worldwide. N6-methyladenosine (m6A) may participate extensively in tumor progression.

Methods: To reveal the landscape of tumor immune microenvironment (TIME), ESTIMATE analysis, ssGSEA algorithm, and the CIBERSORT method were used. Taking advantage of consensus clustering, two different HCC categories were screened. We analyzed the correlation of clustering results with TIME and immunotherapy. Then, we yielded a risk signature by systematical bioinformatics analyses. Immunophenoscore (IPS) was implemented to estimate the immunotherapeutic significance of risk signature.

Results: The m6A-based clusters were significantly correlated with overall survival (OS), immune score, immunological signature, immune infiltrating, and ICB-associated genes. Risk signature possessed robust prognostic validity and significantly correlated with TIME context. IPS was employed as a surrogate of immunotherapeutic outcome, and patients with low-risk scores showed significantly higher immunophenoscores.

Conclusion: Collectively, m6A-based clustering subtype and signature was a robust prognostic indicator and correlated with TIME and immunotherapy, providing novel insight into antitumor management and prognostic prediction in HCC.

• The Cancer Genome Atlas
• hepatocellular carcinoma
• immune checkpoint blockade
• m6A RNA methylation regulators
• prognostic value
• tumor immune microenvironment

Background: Liver cancer stem cells, characterized by self-renewal and initiating cancer cells, were decisive drivers of progression and therapeutic resistance in hepatocellular carcinoma (HCC). However, a comprehensive understanding of HCC stemness has not been identified.

Methods: RNA sequencing information, corresponding clinical annotation, and mutation data of HCC were downloaded from The Cancer Genome Atlas-LIHC project. Two stemness indices, mRNA expression-based stemness index (mRNAsi) and epigenetically regulated-mRNAsi, were used to comprehensively analyze HCC stemness. Estimation of Stromal and Immune Cells in Malignant Tumors using Expression Data and single-sample gene-set enrichment analysis algorithm were performed to characterize the context of tumor immune microenvironment (TIME). Next, differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were employed to identify significant mRNAsi-related modules with hub genes. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathways were analyzed to functionally annotate these key genes. The least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to establish a prognostic signature. Kaplan–Meier survival curves and receiver operating characteristic (ROC) analysis were applied for prognostic value validation. Seven algorithms (XCELL, TIMER, QUANTISEQ, MCPcounter, EPIC, CIBERSORT, and CIBERSORT-ABS) were utilized to draw the landscape of TIME. Finally, the mutation data were analyzed by employing “maftools” package.

Results: mRNAsi was significantly elevated in HCC samples. mRNAsi escalated as tumor grade increased, with poor prognosis presenting the higher stemness index. The stemness-related (greenyellow) modules with 175 hub genes were screened based on DEGs and WGCNA. A prognostic signature was established using LASSO analysis of prognostic hub genes to classify samples into two risk subgroups, which exhibited good prognostic performance. Additionally, prognostic risk-clinical nomogram was drawn to estimate risk quantitatively. Moreover, risk score was significantly associated with contexture of TIME and immunotherapeutic targets. Finally, potential interaction between risk score with tumor mutation burden (TMB) was elucidated.

Conclusion: This work comprehensively elucidated that stemness characteristics served as a crucial player in clinical outcome, complexity of TIME, and immunotherapeutic prediction from both mRNAsi and mRNA level. Quantitative identification of stemness characteristics in individual tumor will contribute into predicting clinical outcome, mapping landscape of TIME further optimizing precision immunotherapy.

• hepatocellular carcinoma
• immunotherapy
• liver cancer stem cells
• prognosis
• tumor immune microenvironment

• cancer
• epigenome
• genome
• hepatocellular carcinoma
• immune checkpoint inhibitors
• immune evasion
• immunotherapy
• molecular targeted agents
• oncogenic signaling pathway
• tumor immune microenvironment

• 21K07184 Japan Society for the Promotion of Science
• 01 Smoking Research Foundation

• cancer
• epigenome
• genome
• hepatocellular carcinoma
• immune checkpoint inhibitors
• immune evasion
• immunotherapy
• molecular targeted agents
• oncogenic signaling pathway
• tumor immune microenvironment

• Angiogenesis inhibitors
• Hepatocellular carcinoma
• Immunomodulation
• Immunosuppressing
• Targeting strategies
• Traditional chinese medicine
• Tumor microenvironment

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Studies have shown that bradykinin (BK) is highly expressed in liver cancer. We designed the novel BK receptor inhibitors J051-71 and J051-105, which reduced the viability of liver cancer cells and inhibited the formation of cancer cell colonies. J051-71 and J051-105 reduced cell proliferation and induced apoptosis in HepG2 and BEL-7402 cells, which may be due to the inhibition of the extracellular regulated protein kinase (ERK) signaling pathway. In addition, these BK receptor inhibitors reversed the cell proliferation induced by BK in HepG2 and BEL-7402 cells by downregulating B1 receptor expression. Inhibiting B1 receptor expression decreased the protein levels of p-ERK and reduced the malignant progression of HCC, providing a potential target for HCC therapy.

• ERK signaling pathway
• apoptosis
• bradykinin B1 receptor
• bradykinin receptor inhibitor
• hepatocellular carcinoma

• Antineoplastic Agents/pharmacology
• Apoptosis/drug effects
• Bradykinin Receptor Antagonists/chemical synthesis
• Bradykinin Receptor Antagonists/chemistry
• Bradykinin Receptor Antagonists/pharmacology
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/metabolism
• Cell Line, Tumor
• Cell Proliferation/drug effects
• Cell Survival/drug effects
• Extracellular Signal-Regulated MAP Kinases/metabolism
• Humans
• Inhibitory Concentration 50
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• MAP Kinase Signaling System/drug effects

Overexpression of Centromere Protein F (CENPF) is associated with tumorigenesis of many human malignant tumors. But the molecular mechanism and prognostic value of CENPF in patients with hepatocellular carcinoma (HCC) are still unclear. In this essay, expression of CENPF in HCC tumors were evaluated in a series of databases, including GEO, TCGA, Oncomine, GEPIA, The Human Protein Atlas and Kaplan-Meier plotter. It was apparent that mRNA and protein expression levels of CENPF were significantly increased in patients with HCC and were manifestly associated with the tumor stage of HCC. Aberrant expressions of CENPF were significantly linked with worse overall survival (OS) and progression-free survival (PFS) in HCC patients. Then, immunohistochemistry of CENPF in human HCC samples was carried out to suggest that CENPF protein was over-expressed in HCC tissues, compared with paired adjacent non-cancerous samples. And small interfering RNAs of CENPF in the human HepG2 cells were further performed to reveal that down-regulation of CENPF significantly inhibited cell proliferation, cell migration, and cell invasion, but slightly promoted cell apoptosis in human HepG2 cells. Moreover, the gene-set enrichment analysis (GSEA) was conducted to probe the biology process and molecular signaling pathway of CENPF in HCC. The GSEA analysis pointed out that CENPF was principally enriched in cell cycle and closely related to E2F1 and CDK1 in the regulation of cell cycle, especially during G2/M transition of mitosis in HCC. Additionally, immune infiltration analysis by CIBERSORTx revealed that mutilpe immune cells, including T_reg, etc., were significantly different in HCC samples with CENPF^high, compared with CENPF^low. These results collectively demonstrated that CENPF might serve as a potential prognostic biomarker and novel therapeutic target for HCC. However, further research is needed to validate our findings and promote the clinical application of CENPF in HCC.

• CENPF
• HCC
• bioinformatics analysis.
• biomarker
• hepatocellular carcinoma
• prognostic value
• survival

• cancer genetics
• tumour biomarkers

• Apoptosis
• Carcinoma, Hepatocellular/enzymology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/pathology
• Cell Cycle Proteins/genetics
• Cell Cycle Proteins/metabolism
• Cell Movement
• Cell Plasticity
• Cell Proliferation
• Databases, Genetic
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Glycolysis
• Hep G2 Cells
• Humans
• Killer Cells, Natural/immunology
• Killer Cells, Natural/metabolism
• Liver Neoplasms/enzymology
• Liver Neoplasms/genetics
• Liver Neoplasms/immunology
• Liver Neoplasms/pathology
• Neoplasm Invasiveness
• PTEN Phosphohydrolase/genetics
• PTEN Phosphohydrolase/metabolism
• Phenotype
• Protein Serine-Threonine Kinases/genetics
• Protein Serine-Threonine Kinases/metabolism
• Proto-Oncogene Proteins/genetics
• Proto-Oncogene Proteins/metabolism
• Signal Transduction
• Tumor Microenvironment
• Tumor-Associated Macrophages/enzymology
• Tumor-Associated Macrophages/immunology
• Tumor-Associated Macrophages/pathology
• Up-Regulation
• Polo-Like Kinase 1

• Natural Science Foundation of Hainan province(820MS130)

• tumour biomarkers
• liver cancer

• Biomarkers, Tumor/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Cell Proliferation
• Female
• Humans
• Intercellular Adhesion Molecule-1/metabolism
• Killer Cells, Natural/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Male
• Middle Aged
• RNA, Circular
• Transfection

• National Natural Science Foundation of China (National Science Foundation of China)
• the Medical and Health Technology Projects in Zhejiang, China [Grant Number: 2020KY1052]

• Cancer
• DNA methylation
• Epigenetic
• Epigenetic drugs
• Kethotherapy
• Ketogenic diet
• Ketone bodies

• Circadian Rhythm/physiology
• DNA Methylation/physiology
• Diet, Ketogenic
• Epigenesis, Genetic/physiology
• Humans
• Neoplasms/diet therapy
• Neoplasms/immunology
• Neoplasms/metabolism

• Cancer stem cell
• Cell signal
• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Mutation

• Diagnostic
• Hepatocellular carcinoma
• Hypoxia
• Immune microenvironment
• Prognostic

• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Hypoxia/genetics
• Kaplan-Meier Estimate
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics
• Neoplasm Recurrence, Local/genetics
• Prognosis
• Tumor Microenvironment

• Cancer stem cell
• Cell signal
• Hepatocellular carcinoma
• Immune checkpoint inhibitors
• Mutation

• genetic alteration
• hepatocellular carcinoma
• immune checkpoint inhibitor
• immune phenotype
• molecular classification
• oncogenic signal
• stem cell marker
• β-catenin

• 18K07922 a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science
• 18 Smoking Research Foundation

• EGFR
• Hepatocellular carcinoma
• drug resistance
• liver cancer stem cell
• miR-206

• ABCB1
• Hepatocellular carcinoma
• MiR-595
• MiRNA
• NF-κB

• Animals
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Cell Proliferation/genetics
• Female
• Gene Expression Regulation, Neoplastic/genetics
• Heterografts
• Humans
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Mice
• Mice, Nude
• MicroRNAs/genetics
• MicroRNAs/metabolism
• NF-kappa B/genetics
• NF-kappa B/metabolism
• Neoplasm Invasiveness/genetics
• Signal Transduction/physiology

• gene therapy
• immunotherapy
• targeted delivery
• ultrasound

• Animals
• Antibodies, Monoclonal/therapeutic use
• Contrast Media/administration & dosage
• Contrast Media/chemistry
• Drug Delivery Systems/methods
• Genetic Therapy/methods
• Humans
• Hydrogen-Ion Concentration
• Immunotherapy/methods
• Neoplasms/diagnostic imaging
• Neoplasms/therapy
• Transfection
• Ultrasonography/methods

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Recent years, circular RNA (circRNA) have been shown to exert vital functions in the pathological progressions of many diseases. A growing number of evidences have identified the representative function of exosomal circRNAs in the physiological state of donor cells, which further induces cellular responses after captured by recipient cells. However, the contributions of circRNAs to HCC remain largely unknown. In vitro and in vivo regulatory roles of circRNA Cdr1as in proliferative and migratory abilities of HCC were evaluated by CCK8, EdU, Transwell and tumourigenicity assays, respectively. Results showed circRNA Cdr1as was highly expressed in HCC cell lines and tissues. Overexpression of circRNA Cdr1as greatly accelerated HCC cells to proliferate and migrate. Mechanistically, we found that Cdr1as could promote the expression of AFP, a well-known biomarker for HCC, by sponging miR-1270. Further studies showed exosomes extracted from HCC cells overexpressing circRNA Cdr1as accelerated the proliferative and migratory abilities of surrounding normal cells. In all, circRNA Cdr1as serves as a ceRNA to promote the progression of HCC. Meanwhile, it is directly transferred from HCC cells to surrounding normal cells via exosomes to further mediate the biological functions of surrounding cells.

• AFP
• circRNA Cdr1as
• competing endogenous RNAs
• exosomes
• hepatocellular carcinoma

• Hepatocellular carcinoma
• Liver cancer stem cell
• SOX9
• Sorafenib
• miR-613

This study aimed to assess whether a diagnosis of cancer interferes with ovarian function prior to the treatment of the disease.

This observational retrospective study used data from medical records of ovarian stimulation cycles performed for purposes of oocyte cryopreservation.

The included patients had a mean age of 35.13±3.72 years and 51.6% of them were aged between 36 and 40 years. More than half of the patients (57.6%) were single and 82.1% had a normal body mass index (BMI). Most women had not become pregnant (85.5%) or had babies (95.1%) or miscarriages (89.6%) prior to cryopreservation. The mean number of oocytes obtained from non-cancer patients was 11.4±8, while for cancer patients the number was 13.8±9. The mean number of frozen mature oocytes was 9.7±7 for the non-cancer group and 11.2±7.2 for the cancer group. The majority (63.1%) of the patients had up to 10 oocytes frozen per cycle. Breast cancer had the highest incidence among the included patients. There was no significant difference in ovarian response between patients with different types of cancer.

The number of harvested and frozen oocytes from cancer and non-cancer patients indicated that in the two groups response to ovarian stimulation was similar.

• Oocyte cryopreservation
• cancer
• fertility preservation
• oncofertility