• Arginine methylation
• MYC
• PRMT1
• hepatocellular carcinoma
• immune escape

• Protein-Arginine N-Methyltransferases/genetics
• Protein-Arginine N-Methyltransferases/metabolism
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/immunology
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Humans
• Proto-Oncogene Proteins c-myc/metabolism
• Proto-Oncogene Proteins c-myc/genetics
• Methylation
• Arginine/metabolism
• Animals
• Mice
• Cell Line, Tumor
• Repressor Proteins/genetics
• Repressor Proteins/metabolism
• Cell Proliferation
• Gene Expression Regulation, Neoplastic
• Immune Evasion
• Tumor Escape
• Cell Movement

• HBXIP
• PARP1
• cisplatin resistance
• hepatoma
• m6A

• Humans
• Cisplatin/pharmacology
• Drug Resistance, Neoplasm
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/genetics
• Liver Neoplasms/drug therapy
• Liver Neoplasms/metabolism
• Liver Neoplasms/genetics
• Poly (ADP-Ribose) Polymerase-1/metabolism
• CCAAT-Enhancer-Binding Proteins/metabolism
• CCAAT-Enhancer-Binding Proteins/genetics
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Animals
• Adenosine/analogs & derivatives
• Adenosine/metabolism
• Cell Line, Tumor
• Mice, Nude
• Mice
• Hep G2 Cells
• Gene Expression Regulation, Neoplastic
• Adaptor Proteins, Signal Transducing

• Pacific Islander
• hepatocellular carcinoma
• liver resection
• liver transplant
• nativity
• risk factors

• U01 CA230690 NCI NIH HHS
• U54 CA143727 NCI NIH HHS
• U54 CA143728 NCI NIH HHS

• landmark analysis
• lenvatinib
• mRECIST
• response status
• surrogate endpoint

• Humans
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/pathology
• Liver Neoplasms/pathology
• Retrospective Studies
• Sorafenib/therapeutic use

• hepatocellular carcinoma
• health insurance
• uninsured
• disparities

• Carcinoma, Hepatocellular/therapy
• Humans
• Liver Neoplasms/therapy
• Retrospective Studies
• Safety-net Providers
• United States
• Vulnerable Populations

• K12 CA226330 NCI NIH HHS
• T32 CA211034 NCI NIH HHS

Hepatocellular carcinoma is 1 of few cancers with rising incidence and mortality in the United States. Little is known about disease presentation and outcomes across the rural-urban continuum.

Using the population-based Surveillance, Epidemiology, and End Results registry, we identified adults with incident hepatocellular carcinoma between 2000 and 2016. Urban, suburban, and rural residence at time of cancer diagnosis were categorized by the Census Bureau’s percent of the population living in nonurban areas. We examined association between place of residence and overall survival. Secondary outcomes were late tumor stage and receipt of therapy.

Of 83 368 incident cases of hepatocellular carcinoma, 75.8%, 20.4%, and 3.8% lived in urban, suburban, and rural communities, respectively. Median survival was 7 months (interquartile range = 2-24). All stage and stage-specific survival differed by place of residence, except for distant stage. In adjusted models, rural and suburban residents had a respective 1.09-fold (95% confidence interval [CI] = 1.04 to 1.14; P < .001) and 1.08-fold (95% CI = 1.05 to 1.10; P < .001) increased hazard of overall mortality as compared with urban residents. Furthermore, rural and suburban residents had 18% (odds ratio [OR] = 1.18, 95% CI = 1.10 to 1.27; P < .001) and 5% (OR = 1.05, 95% CI = 1.02 to 1.09; P = .003) higher odds of diagnosis at late stage and were 12% (OR = 0.88, 95% CI = 0.80 to 0.94; P < .001) and 8% (OR = 0.92, 95% CI = 0.88 to 0.95; P < .001) less likely to receive treatment, respectively, compared with urban residents.

Residence in a suburban and rural community at time of diagnosis was independently associated with worse indicators across the cancer continuum for liver cancer. Further research is needed to elucidate the primary drivers of these rural-urban disparities.

• Hepatocellular carcinoma economic burden treatment patterns

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/economics
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/economics
• Carcinoma, Hepatocellular/therapy
• Chemoembolization, Therapeutic/economics
• Costs and Cost Analysis
• Female
• Health Care Costs/statistics & numerical data
• Humans
• Liver Neoplasms/economics
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Pregnancy
• Sorafenib/economics
• Sorafenib/therapeutic use
• United States

Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo. circARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p. In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.

• HCC
• ceRNA
• chemoresistance
• circARNT2
• circRNA
• cisplatin
• miR-155-5p

• Drug-eluting beads
• Epirubicin
• Hepatocellular carcinoma
• Transcatheter arterial chemoembolization

• Disparities
• Liver transplantation
• Medicaid
• Medicare
• Private insurance

• Liver cancer
• health disparity
• morbidity
• nutrition and health

• SC1 CA193758 NCI NIH HHS
• U54 CA118638 NCI NIH HHS

• Hepatic arterial infusion chemotherapy
• Hepatocellular carcinoma
• Modified RECIST
• Objective response
• Sorafenib

• cirrhosis
• hepatitis C
• hepatocellular carcinoma
• insurance
• socioeconomic status

• Aged
• Carcinoma, Hepatocellular/etiology
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/therapy
• Female
• Hepatitis B/complications
• Hepatitis B/mortality
• Hepatitis B/therapy
• Hepatitis C/complications
• Hepatitis C/mortality
• Hepatitis C/therapy
• Humans
• Insurance Coverage
• Insurance, Health
• Kaplan-Meier Estimate
• Liver Neoplasms/etiology
• Liver Neoplasms/mortality
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/mortality
• Non-alcoholic Fatty Liver Disease/therapy
• Prognosis
• Proportional Hazards Models
• Social Class

• UL1 TR001863 NCATS NIH HHS
• CA160741 United States Department of Defense
• United States Department of Defense

To determine if racial disparities continue to exist in the treatment of hepatocellular carcinoma (HCC).

A retrospective database analysis using the Nationwide Inpatient Sample was performed including patients with a primary diagnosis of HCC. Univariate and multivariate analyses were utilized to determine racial disparities in liver decompensation, treatment, inpatient mortality, and metastatic disease.

A total of 62604 patients with HCC were included consisting of 32428 Caucasian, 9726 African-American, 8988 Hispanic, and 11462 patients of other races. Caucasian patients were more likely to undergo curative therapies of liver transplant (OR: 2.66, 95%CI: 1.92-3.68), resection (OR: 1.82, 95%CI: 1.48-2.23), and ablation (OR: 1.77, 95%CI: 1.36-2.30) than African-American patients. Hispanic patients were more likely to undergo transplant (OR: 2.18, 95%CI: 1.40-3.39) and ablation (OR: 1.46, 95%CI: 1.05-2.03) than African-American patients. Patients of other races were more likely to receive a liver transplant (OR: 2.41, 95%CI: 1.62-3.61), resection (OR: 1.79 95%CI: 1.39-2.32), and ablation (OR: 2.03, 95%CI: 1.47-2.80) than African-American patients. There are no differences in the rates of transarterial chemoembolization between races.

Racial disparities in HCC treatment exist despite emphasis to support equality in healthcare. African-American patients are less likely to undergo curative treatments for HCC.

• Racial disparity
• Hepatocellular carcinoma
• Liver transplantation
• Resection
• Ablation

• Intermediate-stage hepatocellular carcinoma
• Kyoto criteria
• Pretreatment
• Transarterial chemoembolization
• Transplantation

Proton coupled oligopeptide transporter 1 (PEPT1) is a member of the peptide transporter superfamily and plays important role in the absorption of oligopeptide and peptidomimetic drugs. Our previous research verified that PEPT1 expressed specifically in human Hepatocellular carcinoma (HCC) tissue and cell lines and showed potential transport activity to be a new candidate of the tumor therapeutic target. In this study, we aim to explore the feasibility of a novel tumor target therapeutic strategy: Targeting PEPT1 to improve the antitumor efficacy of Doxorubicin in human HCC therapy. First, Doxorubicin was conjugated with Glycylglycylglycine (Gly-Gly-Gly) − a tripeptide which was known as the substrate of PEPT1 and characterized by HPLC and MS successfully. Doxorubicin-tripeptide conjugate was then observed to clarify the target delivery by PEPT1 and the antitumor effect on human hepatocarcinoma in vivo and in vitro. Furthermore, the improvement of the toxic and side effect of Doxorubicin after conjugation was also evaluated by some biochemical tests. Our results reveal that targeting PEPT1 may contribute to the efficient delivery of Doxorubicin to hepatocarcinoma cells and the reduction of drug toxicity. PEPT1 has the prospect to be a novel target of HCC therapy.

• doxorubicin
• hepatocellular carcinoma (HCC)
• proton coupled oligopeptide transporter 1
• target therapy
• toxicity

Proton-coupled oligopeptide transporter 1 (PEPT1) is a membrane protein which expressed predominantly in intestine and recognized as the target of dietary nutrients (di/tripeptide) or peptidomimetic drug for delivery. The information on the existence of PEPT1 in carcinomas were limited. Our study aimed to investigate the expression profile and transport activity of PEPT1 both in human hepatocarcinoma tissues and cell lines. Western blotting and an immunofluorescence assay revealed the high level of PEPT1 protein expression in hepatocarcinoma Bel-7402, SMMC-7721, HepG2, HEP3B, SK-HEP-1 cell lines. Quantitative real time PCR showed the mRNA expression of PEPT1 in Bel-7402, SMMC-7721, HepG2, HEP3B, SK-HEP-1 cells. High level PEPT1 expression in hepatocarcinoma patient samples were observed by Immunohistology and showed a significant correlation between protein level and pathological grade. Functional activities were also studied using D-Ala-Lys-AMCA (a substrate of peptide transporter) in above five hepatocarcinoma cell lines. The uptake tests performed by fluorescent microscopy suggested that PEPT1 can transport both D-Ala-Lys-AMCA into the hepatocarcinoma cells and the uptake can be competitively inhibited by three PEPT1 substrates (Gly-sar, Gly-gln and Glyglygly). In conclusion, our findings provided the novel information on the expression and function of PEPT1 in human hepatocarcinoma and expanded the potential values for tumor specific drug delivery.

• expression
• primary hepatocarcinoma
• proton-coupled oligopeptide transporter 1
• tumor-targeted therapy

• Bridging therapy
• Hepatocellular carcinoma
• Liver transplantation

• Hepatocellular carcinoma
• epithelial-mesenchymal transition
• marker
• metastasis
• protein arginine N-methyltransferase 1
• targeted therapy

To describe racial/ethnic differences in treatment and survival among liver cancer patients in a population-based cancer registry.

Invasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White (White, n = 12710), Hispanic (n = 8500), Chinese (n = 2723), non-Hispanic Black (Black, n = 2609), Vietnamese (n = 2063), Filipino (n = 1479), Korean (n = 1099), Japanese (n = 658), American Indian/Alaskan Native (AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian (n = 233), South Asian (n = 190), Hawai`ian/Pacific Islander (n = 172), Thai (n = 95), and Other Asian (n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.

After adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio (OR) = 0.30, 95%CI: 0.17-0.53], Cambodian (OR = 0.65, 95%CI: 0.45-0.96), AIAN (OR = 0.66, 95%CI: 0.46-0.93), Black (OR = 0.76, 95%CI: 0.67-0.86), and Hispanic (OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese (OR = 1.58, 95%CI: 1.42-1.77), Koreans (OR = 1.45, 95%CI: 1.24-1.70), Japanese (OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese (OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio (HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians (HR = 1.35, 95%CI: 1.16-1.58), and Blacks (HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese (HR = 0.82, 95%CI: 0.77-0.86), Filipinos (HR = 0.84, 95%CI: 0.78-0.90), Vietnamese (HR = 0.85, 95%CI: 0.80-0.90), Koreans (HR = 0.90, 95%CI: 0.83-0.97), and Hispanics (HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.

Disaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities.

• Disparities
• Treatment
• Survival
• Liver cancer
• Hepatocellular carcinoma

• Adult
• Black or African American
• Aged
• Asian
• California
• Carcinoma, Hepatocellular/ethnology
• Carcinoma, Hepatocellular/mortality
• Female
• Geography
• Health Status Disparities
• Healthcare Disparities
• Hispanic or Latino
• Humans
• Kaplan-Meier Estimate
• Liver Neoplasms/ethnology
• Liver Neoplasms/mortality
• Male
• Middle Aged
• Odds Ratio
• Registries
• Risk Factors
• SEER Program
• Social Class
• Treatment Outcome
• United States

• P30 CA093373 NCI NIH HHS

• EMT
• HCC
• PRMT1
• miR-503