Liver Cancer Cases Research Articles

Global burden of primary liver cancer by five etiologies and global prediction by 2035 based on global burden of disease study 2019.

BackgroundUsing data from the global burden of disease (GBD) between 1990 and 2019 to report the leading etiological factors and hazards for liver cancer by HBV (LCHB), HCV (LCHC), alcoholic use (LCAL), NASH (LCNA), and other causes (LCOT).MethodThe estimated annual percentage change (EAPC) and age‐standardized incidence rate (ASR) in different districts, sex, and age are used to quantify the change of etiologies of liver cancer. Age‐period‐cohort models were performed to predict the primary liver cancer incidence and case numbers.ResultsBased on the GBD database of the whole world for the five etiologies of liver cancer in 2019, the percentage of incidence of LCAL, LCHB, LCHC, LCNA, and LCOT are 18.4%, 41%, 28.5%, 6.8%, and 5.3%, respectively. Fiver etiologies of liver cancer show gender differences, with LCHB and LCAL being more prevalent in men, and LCHC, LCNA being more prevalent in women. Besides, live cancer of males is because of alcohol using and smoking, while the reason of liver cancer of females is drug use, high BMI and high fasting plasma glucose. Interestingly, the incidence of LCHC in women over 85 years old, LCNA in women over 75 years old, and LCOT in women over 75 years old were all higher than that in men. According to the future prediction, the incidence rate of liver cancer itself, as well as the five causes of liver cancer, tends to decrease gradually after 2019, while the incidence rate of LCNA in males will continue to increase until 2025.ConclusionsThe incidence of liver cancer has been increasing and its major causes vary considerably at global, regional, or national levels, also vary by gender and age group.

Oncogenic Mutation BRAF V600E Changes Phenotypic Behavior of THLE-2 Liver Cells through Alteration of Gene Expression.

The accumulation of mutations in cancer driver genes, such as tumor suppressors or proto-oncogenes, affects cellular homeostasis. Disturbances in the mechanism controlling proliferation cause significant augmentation of cell growth and division due to the loss of sensitivity to the regulatory signals. Nowadays, an increasing number of cases of liver cancer are observed worldwide. Data provided by the International Cancer Genome Consortium (ICGC) have indicated many alterations within gene sequences, whose roles in tumor development are not well understood. A comprehensive analysis of liver cancer (virus-associated hepatocellular carcinoma) samples has identified new and rare mutations in B-Raf proto-oncogene (BRAF) in Japanese HCC patients, as well as BRAF V600E mutations in French HCC patients. However, their function in liver cancer has never been investigated. Here, using functional analysis and next generation sequencing, we demonstrate the tumorigenic effect of BRAF V600E on hepatocytes (THLE-2 cell line). Moreover, we identified genes such as BMP6, CXCL11, IL1B, TBX21, RSAD2, MMP10, and SERPIND1, which are possibly regulated by the BRAF V600E-mediated, mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK) signaling pathway. Through several functional assays, we demonstrate that BRAF L537M, D594A, and E648G mutations alone are not pathogenic in liver cancer. The investigation of genome mutations and the determination of their impact on cellular processes and functions is crucial to unraveling the molecular mechanisms of liver cancer development.

Real-world study evaluating the incidence of liver damage conditions in patients with primary liver cancer using immune checkpoint inhibitor-based combination therapy

Objective: To evaluate the incidence of immune checkpoint inhibitor-based combination therapy-induced liver damage in patients with primary liver cancer. Methods: Clinical data of 65 hospitalized cases of primary liver cancer treated with programmedcelldeath-1its ligand programmed death-ligand 1(PD-1/PD-L1) antibody in the Department of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University from January 1, 2018 to March 31, 2021 were retrospectively analyzed. The degree of liver injury before and after treatment was assessed according to CTCAE v5.0. Patients were grouped according to gender, age, presence or absence of cirrhosis, baseline Child-Pugh score, BCLC stage, and treatment regimen to compare the incidence of liver injury under different conditions. The χ (2) test or rank-sum test was used for comparison among multiple groups. Results: 46 cases (70.77%) had liver damage of any grade according to the CTCAE V5.0 criteria during the treatment and observation period. All 6 cases who received standardized anti-hepatitis B virus (HBV) treatment developed liver damage. 10 (15.38%), 15 (23.08%), 19 (29.23%), and 2 (3.08%) cases had grade 1, 2, 3, and 4 liver damage respectively. There was no statistically significant difference in the incidence of liver damage between male and female patients (68.33% and 100%, P = 0.180). There was no statistically significant difference in the incidence of liver damage among different age groups (P = 0.245). The incidence of liver damage in cirrhotic and non-cirrhotic group was 72.22%, and 63.64% (P = 0.370), respectively. The incidence of liver damage in patients with baseline Child-Pugh class A, B, and C were 71.43%, 61.11% and 100%, respectively, and the difference was not statistically significant (P = 0.878). The incidence of liver damage was not statistically significantly different under different BCLC stages (P = 1.000). The incidence of liver damage in the PD-1/PD-L1 antibody monotherapy, PD-1/PD-L1 antibody combined with targeted drug therapy, and PD-1/PD-L1 antibody combined with TACE/radiofrequency ablation treatment group were 60.00%, 67.85%, and 86.67%, respectively. There was no statistically significant difference in the incidence of liver damage between the treatment regimen (P = 0.480). Conclusion: Immune checkpoint inhibitor therapy-induced liver damage is common in patients with primary liver cancer; however, it rarely severely endangers the patient's life. Additionally, patient's gender, age, presence or absence of cirrhosis, baseline liver function, BCLC stage and the immunotherapy regimen has no effect on the incidence of immune-related liver damage.

Dose-response relationship between fat distribution and liver cancer incidence: A prospective cohort study in Chinese men

BackgroundBased on a prospective cohort study in middle-aged Chinese men, the current study characterized the dose-response relationships between fat distribution measurements and the incidence of primary liver cancer. MethodsHazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by Cox regression models for the association between waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body roundness index (BRI) with liver cancer incidence. Dose-response curves were characterized using a restricted cubic spline function. ResultsAfter a mean follow-up time of 11.9 (SD = 2.4) years, 440 liver cancer cases were identified from 60,625 participants. WC, WHtR, ABSI, and BRI were found to be associated with an increased risk of liver cancer at a given level of body mass index (BMI), with multivariable-adjusted HRs of 1.19 (95% CI: 1.01–1.41), 1.26 (95% CI: 1.02–1.50), 1.12 (95% CI: 1.05–1.23) and 1.28 (95% CI: 1.08–1.53) for per SD increment, respectively. Dose-response curves suggested that the risk increased rapidly above the median levels of WC, WHtR, and BRI. For ABSI, the risk decreased from the minimum level to about the 35th percentile and increased slowly thereafter. ConclusionsThe current study suggested an association between abdominal obesity in middle age and increased risk of primary liver cancer at a given level of BMI. WHtR and BRI were better predictors of liver cancer risk compared with WC and ABSI.

Roles of BMI1 in the Initiation, Progression, and Treatment of Hepatocellular Carcinoma.

Liver cancer has high rates of morbidity and mortality, and its treatment is a global health challenge. Hepatocellular carcinoma (HCC) accounts for 90% of all primary liver cancer cases. B-lymphoma Mo-MLV insertion region 1 (BMI1) has been identified as a proto-oncogene, which contributes to the initiation and progression of many malignant tumors. BMI1 expression is upregulated in HCC, and it influences the occurrence and development of HCC by various mechanisms, such as the INK4a/ARF locus, NF-κB signaling pathway, and PTEN/PI3K/AKT signaling pathway. In addition, the expression of BMI1 is related to prognosis and recurrence of HCC. Hence, there is clear evidence that BMI1 is a novel and valid therapeutic target for HCC. Accordingly, the development of therapeutic strategies targeting BMI1 has been a focus of recent research, providing new directions for HCC treatment. This review summarizes the role of BMI1 in the occurrence and treatment of HCC, which will provide a basis for using BMI1 as a potential target for the development of therapeutic strategies for HCC.

Primary Malignant Liver Tumors: eight-year experience in a Pediatric Hospital in Brazil. A cross-sectional study.

liver tumors are rare neoplasms in childhood (1-2%), and about 2/3 are malignant. Hepatoblastoma (HB) is the most frequent, followed by hepatocellular carcinoma (HCC). In both, the main treatment is surgical resection. Currently, chemotherapy and liver transplantation have improved outcomes. study of the epidemiological profile and evolution of liver cancer cases in a referral pediatric hospital. a retrospective survey of medical records of patients aged up to 18 years with a diagnosis of primary malignant hepatic neoplasm between 2012 and 2020, carried out in the largest exclusively pediatric hospital in Brazil. a total of 13 patients with malignant liver tumors (HB 12, HCC 1) were treated. Of the HB cases, 66,7% were male, with a mean age of 2 years and the main alteration in the palpable abdominal mass. Tumors involved an average of 3 liver segments, more in the right lobe (54%). Only one patient was treated with surgery without neoadjuvant therapy, another one underwent transplantation like the first treatment, and another 2 required liver transplantation as a rescue. The middle follow-up time of patients with HB was 39 months and only 1 case died due to febrile neutropenia. The 5-year overall and disease-free survival was 91.7% and 81.5%, respectively. Advanced staging at the time of diagnosis has always been a poor prognostic factor in patients with primary malignant liver tumors. However, the results and survival have improved with the advancement of chemotherapy, surgical technique, and liver transplantation.

Relationship Between Fish Oil Use and Incidence of Primary Liver Cancer: Findings From a Population-Based Prospective Cohort Study.

Background: N-3 long-chain polyunsaturated fatty acids (LCPUFAs) prevented non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) in studies of mouse models. We examined prospective relationships between fish oil use and risk of primary liver cancer and the major histological subtypes, such as HCC and intrahepatic cholangiocarcinoma (ICC).Methods: We included 434,584 middle-aged and older men and women who were free of cancer at recruitment of the UK Biobank (2006–2010). Information on fish oil use and other dietary habits was collected via questionnaires. Cox proportional hazards models were used to compute the hazard ratio (HR) and 95% CI of liver cancer associated with fish oil use, with adjustment for socio-demographic, lifestyle, dietary, and other clinical risk factors.Results: At baseline, 31.4% of participants reported regular use of fish oil supplements. During a median of 7.8 years of follow-up, 262 incident liver cancer cases were identified, among which 127 were HCC and 110 were ICC cases. As compared with non-users, fish oil users had a significantly 44% (95% CI: 25–59%) lower risk of total liver cancer, and 52% (95% CI: 24–70%) and 40% (95% CI: 7–61%) lower risk of HCC and ICC, respectively. Higher intake of oily fish also was associated with a lower risk of HCC (≥2 vs. <1 serving/week: HR = 0.46; 95% CI: 0.23–0.96; P-trend = 0.027) but not ICC (P-trend = 0.96).Conclusion: Habitual use of fish oil supplements was associated lower risk of primary liver cancer regardless of cancer histological subtypes, potentially supporting a beneficial role of dietary n-3 LCPUFAs in liver cancer prevention.

Global, regional and national burden of primary liver cancer by subtype

IntroductionHepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA) are the two main histological subtypes of primary liver cancer. Estimates of the burden of liver cancer by subtype are needed to facilitate development and evaluation of liver cancer control globally. We provide worldwide, regional and national estimates of HCC and iCCA incidence using high-quality data. MethodsWe used population-based cancer registry data on liver cancer cases by histological subtype from 95 countries to compute the sex- and country-specific distributions of HCC, iCCA and other specified histology. Subtype distributions were applied to estimates of total liver cancer cases for 2018 from the Global Cancer Observatory. Age-standardised incidence rates (ASRs) were calculated. ResultsThere were an estimated 826,000 cases of liver cancer globally in 2018: 661,000 HCC (ASR 7.3 cases per 100,000); 123,000 iCCA (ASR 1.4) and 42,000 other specified histology (ASR 0.5). HCC contributed 80% of the world total liver cancer burden followed by iCCA (14.9%) and other specified histology (5.1%). HCC rates were highest in Eastern Asia (ASR 14.8), Northern Africa (ASR 13.2) and South-Eastern Asia (ASR 9.5). Rates of iCCA were highest in South-Eastern Asia (ASR 2.9), Eastern Asia (ASR 2.0), Northern Europe, the Caribbean and Central America and Oceania (ASR all 1.8). ConclusionWe have shown the importance of uncovering the distinct patterns of the major subtypes of liver cancer. The use of these estimates is critical to further develop public health policy to reduce the burden of liver cancer and monitor progress in controlling HCC and iCCA globally.

LINC00491 promotes cell growth and metastasis through miR-324-5p/ROCK1 in liver cancer

BackgroundLINC00491 was involved in some tumors development, but its function in liver cancer has not been reported. This study aimed to investigate LINC00491 expression and function in liver cancer progression.MethodsSixty liver cancer cases were enrolled. LINC00491, miR-324-5p and rho-associated kinase 1 (ROCK1) expression in liver cancer patients and cells were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. HUH-7 and SK-Hep-1 cells were transfected to modulate LINC00491, miR-324-5p and ROCK1 expression. Cell counting kit-8 assay, colony formation assay, wound healing assay, Transwell experiment, Tunel assay and flow cytometry were performed to detected HUH-7 and SK-Hep-1 cells proliferation, migration, invasion, apoptosis and cell cycle. Biotin-RNA pull-down assay and Dual-Luciferase Reporter Assay was performed to detect the binding among LINC00491, miR-324-5p and ROCK1. Xenograft tumor and lung metastasis was performed using nude mice. Xenograft tumor and lung tissues of mice were experienced immunohistochemistry and hematoxylin–eosin staining.ResultsLINC00491 was highly expressed in liver cancer cases, associating with poor prognosis. si-LINC00491 inhibited proliferation, colony formation, invasion, migration, and induced cell cycle G1 arrest and apoptosis in HUH-7 and SK-Hep-1 cells. LINC00491 overexpression showed opposite effects. LINC00491 promoted ROCK1 expression by reducing miR-324-5p. miR-324-5p up-regulation or ROCK1 knockdown reversed LINC00491 promotion on liver SK-Hep-1 cells malignant phenotype. LINC00491 facilitated xenograft tumor growth and lung metastasis in mice.ConclusionLINC00491 was highly expressed in liver cancer patients, associating with poor prognosis. LINC00491 facilitated liver cancer progression by sponging miR-324-5p/ROCK1. LINC00491 might be a potential treatment target of liver cancer.

CircFOXM1 promotes proliferation and metastasis of hepatocellular carcinoma via regulating miR-1179/SPAG5 axis

Hepatocellular carcinoma (HCC) predominantly occurs in patients with chronic liver disease, accounting for 70–90% of all liver cancer cases. The role of circFOXM1/miR-1179/SPAG5 axis in HCC has not been reported. This study aimed to explore the regulatory mechanism of circFOXM1 in HCC proliferation and metastasis. RNA polymerase inhibitor actinomycin D and RNase R exonuclease were used to identify circFOXM1 in HCC cells. The qRT-PCR was used to detect circFOXM1 expression. Specific siRNA for circFOXM1 was designed, and the sequence of circFOXM1 was inserted in pLCDH-ciR to overexpress circFOXM. Cell proliferation was detected by CCK8 in vitro, by tumor volume and tumor weight of HCC xenograft in vivo. Cell migration was detected by transwell test. Binding status of circFOXM1 with miR-1179 was detected by luciferase reporter gene assay. Rescue experiments were applied to identify the oncogenic mechanism of circFOXM1 in HCC cells. Actinomycin D assay confirmed the cyclization of circFOXM1. RNase R treatment showed that circFOXM1 was not affected by RNase R exonuclease. CCK8 assay, tumor volume and tumor weight showed that circFOXM1 effectively promoted HCC cell proliferation. Transwell assay showed that circFOXM effectively promoted migration and invasion abilities of HCC cells. Luciferase reporter gene activity assay showed that miR-1179 had complementary binding sites with circFOXM1 and SPAG5. CircFOXM1 silencing inhibited malignant phenotypes in HCC cells were partly rescued by either miR-1179 silencing or SPAG5 overexpression. CircFOXM1 promoted HCC cell proliferation and metastasis by regulating miR-1179/SPAG5 axis.

Role of hsa_circ_0066966 in proliferation and migration of hepatitis B virus-related liver cancer cells.

A large proportion of liver cancer cases is caused by hepatitis B virus (HBV) infection. In recent years, an increasing number of reports have indicated that circular RNAs (circRNAs) exert regulatory effects in cancer development, whereas the role of circRNAs in HBV-positive liver cancer requires further investigation. In the present study, abnormally expressed circRNAs were identified in HBV-positive liver cancer cells through microarray analysis. A total of 1,493 differentially expressed circRNAs [absolute fold-change (FC) ≥2] in HBV-positive liver cancer cells were detected, of which 171 were upregulated and 1,322 were downregulated. Subsequently, Gene Ontology enrichment analysis indicated that the genes of dysregulated circRNAs were mainly involved in regulating Sertoli cell differentiation and development, as well as telomeric DNA binding. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that most of these genes were enriched in cancer-related signaling pathways, including the MAPK and Hippo signaling pathways. Next, the expression levels of the top-10 dysregulated circRNAs were verified in HBV-positive liver cancer cells through reverse transcription-quantitative PCR. Among them, hsa_circ_0066966 had the highest absolute Log2FC value and was abnormally increased in HBV-positive liver cancer cells. Functional experiments further verified that knockdown of hsa_circ_0066966 had a significant inhibitory effect on the proliferation and migration of HBV-positive liver cancer cells. By contrast, overexpression of hsa_circ_0066966 in HBV-negative liver cancer cells resulted in the opposite effect. In conclusion, in the present study, comprehensive circRNA profiling in HBV-positive liver cancer cells indicated that hsa_circ_0066966 may regulate the progression of HBV-positive liver cancer.

Scalable Optimization Methods for Incorporating Spatiotemporal Fractionation into Intensity-Modulated Radiotherapy Planning

It has been recently shown that an additional therapeutic gain may be achieved if a radiotherapy plan is altered over the treatment course using a new treatment paradigm referred to in the literature as spatiotemporal fractionation. Because of the nonconvex and large-scale nature of the corresponding treatment plan optimization problem, the extent of the potential therapeutic gain that may be achieved from spatiotemporal fractionation has been investigated using stylized cancer cases to circumvent the arising computational challenges. This research aims at developing scalable optimization methods to obtain high-quality spatiotemporally fractionated plans with optimality bounds for clinical cancer cases. In particular, the treatment-planning problem is formulated as a quadratically constrained quadratic program and is solved to local optimality using a constraint-generation approach, in which each subproblem is solved using sequential linear/quadratic programming methods. To obtain optimality bounds, cutting-plane and column-generation methods are combined to solve the Lagrangian relaxation of the formulation. The performance of the developed methods are tested on deidentified clinical liver and prostate cancer cases. Results show that the proposed method is capable of achieving local-optimal spatiotemporally fractionated plans with an optimality gap of around 10%–12% for cancer cases tested in this study. Summary of Contribution: The design of spatiotemporally fractionated radiotherapy plans for clinical cancer cases gives rise to a class of nonconvex and large-scale quadratically constrained quadratic programming (QCQP) problems, the solution of which requires the development of efficient models and solution methods. To address the computational challenges posed by the large-scale and nonconvex nature of the problem, we employ large-scale optimization techniques to develop scalable solution methods that find local-optimal solutions along with optimality bounds. We test the performance of the proposed methods on deidentified clinical cancer cases. The proposed methods in this study can, in principle, be applied to solve other QCQP formulations, which commonly arise in several application domains, including graph theory, power systems, and signal processing.

Phytochemicals as an Alternative or Integrative Option, in Conjunction with Conventional Treatments for Hepatocellular Carcinoma.

Simple SummaryHepatocellular carcinoma (HCC) is globally ranked as the sixth most diagnosed cancer, and the second most deadly cancer. To worsen matters, there are only limited therapeutic options currently available; therefore, it is necessary to find a reservoir from which new HCC treatments may be acquired. The field of phytomedicine may be the solution to this problem, as it offers an abundance of plant-derived molecules, which show capabilities of being effective against HCC proliferation, invasion, migration, and metastasis. In our review, we collect and analyze current evidence regarding these promising phytochemical effects on HCC, and delve into their potential as future chemotherapies. Additionally, information on the signaling behind these numerous phytochemicals is provided, in an attempt to understand their mechanisms. This review makes accessible the current body of knowledge pertaining to phytochemicals as HCC treatments, in order to serve as a reference and inspiration for further research into this subject.Hepatocellular carcinoma (HCC) is the most abundant form of liver cancer. It accounts for 75–85% of liver cancer cases and, though it ranks globally as the sixth most common cancer, it ranks second in cancer-related mortality. Deaths from HCC are usually due to metastatic spread of the cancer. Unfortunately, there are many challenges and limitations with the latest HCC therapies and medications, making it difficult for patients to receive life-prolonging care. As there is clearly a high demand for alternative therapy options for HCC, it is prudent to turn to plants for the solution, as their phytochemicals have long been used and revered for their many medicinal purposes. This review explores the promising phytochemical compounds identified from pre-clinical and clinical trials being used either independently or in conjunction with already existing cancer therapy treatments. The phytochemicals discussed in this review were classified into several categories: lipids, polyphenols, alkaloids, polysaccharides, whole extracts, and phytochemical combinations. Almost 80% of the compounds failed to progress into clinical studies due to lack of information regarding the toxicity to normal cells and bioavailability. Although large obstacles remain, phytochemicals can be used either as an alternative or integrative therapy in conjunction with existing HCC chemotherapies. In conclusion, phytochemicals have great potential as treatment options for hepatocellular carcinoma.

Molecular Imaging of Tumor Microenvironment to Assess the Effects of Locoregional Treatment for Hepatocellular Carcinoma.

Liver cancer is one of the leading causes of cancer deaths worldwide. Among all primary liver cancers, hepatocellular carcinoma (HCC) is the most common type, representing 75%‐85% of all primary liver cancer cases. Median survival following diagnosis of HCC is approximately 6 to 20 months due to late diagnosis in its course and few effective treatment options. Interventional therapy with minimal invasiveness is recognized as a promising treatment for HCC. However, due to the heterogeneity of HCC and the complexity of the tumor microenvironment, the long‐term efficacy of treatment for HCC remains a challenge in the clinic. Tumor microenvironment, including factors such as hypoxia, angiogenesis, low extracellular pH, interstitial fluid pressure, aerobic glycolysis, and various immune responses, has emerged as a key contributor to tumor residual and progression after locoregional treatment for HCC. New approaches to noninvasively assess the treatment response and assist in the clinical decision‐making process are therefore urgently needed. Molecular imaging tools enabling such an assessment may significantly advance clinical practice by allowing real‐time optimization of treatment protocols for the individual patient. This review discusses recent advances in the application of molecular imaging technologies for noninvasively assessing changes occurring in the microenvironment of HCC after locoregional treatment.

Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality

The relationship between dietary factors and liver disease remains poorly understood. This study evaluated the associations of whole grain and dietary fiber intake with liver cancer risk and chronic liver disease mortality. The National Institutes of Health–American Association of Retired Persons Diet and Health Study cohort recruited 485, 717 retired U.S. participants in 1995–1996. Follow-up through 2011 identified 940 incident liver cancer cases and 993 deaths from chronic liver disease. Compared with the lowest, the highest quintile of whole grain intake was associated with lower liver cancer risk (Hazard ratio [HR]Q5 vs. Q1 = 0.78, 95% confidence interval [CI]: 0.63–0.96) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.44, 95% CI: 0.35–0.55) in multivariable Cox models. Dietary fiber was also associated with lower liver cancer risk (HRQ5 vs. Q1 = 0.69, 95% CI: 0.53–0.90) and chronic liver disease mortality (HRQ5 vs. Q1 = 0.37, 95% CI: 0.29–0.48). Fiber from vegetables, beans and grains showed potential protective effect. Here, we show that higher intake of whole grain and dietary fiber are associated with lower risk of liver cancer and liver disease mortality.

A novel m6A-related prognostic signature for predicting the overall survival of hepatocellular carcinoma patients.

Liver hepatocellular carcinoma (LIHC) comprises most cases of liver cancer with a poor prognosis. N 6‐methyladenosine (m6A) plays important biological functions in cancers. Thus, the present research was aimed to determine biomarkers of m6A regulators that could effectively predict the prognosis of LIHC patients. Based on the data collected from the Cancer Genome Atlas (TCGA) database, the correlation between the mRNA expression levels and copy number variation (CNV) patterns were determined. Higher mRNA expression resulted from the increasing number of 9 genes. Using the univariate Cox regression analysis, 11 m6A regulators that had close correlations with the LIHC prognosis were identified. In addition, under the support of the multivariate Cox regression models and the least absolute shrinkage and selection operator, a 4‐gene (YTHDF2, IGF2BP3, KIAA1429, and ALKBH5) signature of m6A regulators was constructed. This signature was expected to present a prognostic value in LIHC (log‐rank test p value < 0.0001). The GSE76427 (n = 94) and ICGC‐LIRI‐JP (n = 212) datasets were used to validate the prognostic signature, suggesting strong power to predict patients' prognosis for LIHC. To sum up, genetic alterations in m6A regulatory genes were identified as reliable and effective biomarkers for predicting the prognosis of LIHC patients.

Effect of Radiofrequency Ablation with Interventional Therapy of Hepatic Artery on the Recurrence of Primary Liver Cancer and the Analysis of Influencing Factors.

Background The probability of liver cancer recurring in patients after surgery is a serious threat to liver cancer patients. Radiofrequency ablation is widely employed in liver cancer cases. We explored the therapeutic effects and influencing factors of radiofrequency ablation combined with hepatic artery intervention in patients with recurrence of primary liver cancer surgery. Methods 90 patients with primary liver cancer postoperative recurrence admitted to our hospital from January 2014 to February 2017 were selected as the research objects. The patients were randomly divided into the control group (n = 45) and combined treatment group (n = 45). The combined treatment group received radiofrequency ablation combined with hepatic artery interventional therapy, and the control group received hepatic artery interventional therapy. The short-term efficacy, AFP levels before and after treatment, and long-term survival results of the two groups were compared. Single-factor and multifactor analyses of the clinical information of the combined treatment group were carried out to find out the factors affecting the therapeutic effect of radiofrequency ablation combined with hepatic artery intervention on patients with recurrence of primary liver cancer. Results The total effective rate of short-term curative effect of the combined treatment group was higher than the control group, and there was a statistically significant difference existing (P < 0.05). After treatment, two groups of patients' AFP levels were greatly lower than before treatment, the AFP levels of the combined treatment group were significantly lower than the control group, and there was a statistically significant difference (P < 0.05). The survival rates of patients in the combined treatment group at the sixth month, the first year, and the second year after treatment were significantly higher than those of the control group, and there was a statistically significant difference (P < 0.05). The univariate results showed that, in the combined treatment group, there were statistically significant differences between the effective group and the ineffective group in tumor diameter, intact capsule, liver cirrhosis, intrahepatic spread, and tumor adjacent to large blood vessels (P < 0.05). The outcomes of multivariate analysis indicated that tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels were risk factors for ineffective recurrence of patients with primary liver cancer after radiofrequency ablation combined with hepatic artery intervention (P < 0.05). Discussion. Tumor diameter ≥ 3 cm, incomplete capsule, intrahepatic spread, and tumor adjacent to large blood vessels are risk factors for the ineffectiveness of radiofrequency ablation combined with hepatic artery interventional therapy for patients with recurrence of primary liver cancer. It is necessary to increase the range of radiofrequency treatment, increase the temperature of the radiofrequency needle, and strengthen postoperative follow-up interventions based on the specific conditions of the patient's tumor.

Metabolic syndrome and its component traits present gender-specific association with liver cancer risk: a prospective cohort study

Background & AimsLittle is known on the gender-specific effect and potential role of non-linear associations between metabolic syndrome (MetS) components and liver cancer risk. We evaluated these associations based on the UK Biobank cohort.MethodsWe included 474,929 individuals without previous cancer based on the UK Biobank cohort. Gender-specific hazard ratios (HRs) and 95% confidence interval (CIs) were calculated by Cox proportional hazards regression, adjusting for potential confounders. Non-linear associations for individual MetS components were assessed by the restricted cubic spline method.ResultsOver a median follow-up of 6.6 years, we observed 276 cases of liver cancer (175 men, 101 women). MetS [HR 1.48, 95% CI 1.27–1.72] and central obesity [HR 1.65, 95% CI 1.18–2.31] were associated with higher risk of liver cancer in men but not in women. Participants with hyperglycaemia has higher risk of liver cancer. High waist circumference and blood glucose were dose-dependently associated with increased liver cancer risk in both genders. For high density lipoprotein (HDL) cholesterol (both genders) and blood pressure (women), U-shaped associations were observed. Low HDL cholesterol (< 1.35 mmol/L) in men and high HDL cholesterol in women (> 1.52 mmol/L) were associated with increased liver cancer risk.ConclusionsMetS components showed gender-specific linear or U- shaped associations with the risk of liver cancer. Our study might provide evidence for individualized management of MetS for preventing liver cancer.

Primary Liver Cancer in Golestan Province, Northeastern Iran: 13-Year Experience of Golestan Population-Based Cancer Registry (GPCR).

Liver cancer (LC) is among the most common and fatal cancers worldwide. A four-fold increasing trend is reported for LC age-standardized mortality rate (ASMR) in Iran within 1990-2015. In the present study, we aimed to report the incidence rate of LC during the 13-year establishment of the Golestan population-based cancer registry (GPCR). Age-standardized incidence rate (ASIR) per 100000 person-years was calculated using CanReg5 software. The Joint point regression analysis was used to assess the temporal trends in incidence rate of LC. During the study period, GPCR registered 575 of LC cases, of which 373 (64.9%) were men and 297 (51.6%) lived in rural areas. The mean (SD) age of LC in men and women were 60.3 (17.2) and 58.0 (17.1), respectively. The ASIR of LC was significantly higher in men than women (4.7 vs. 2.6; P value<0.01) and a minimal increasing trend in LC incidence was observed in both sexes. The incidence rate of LC was significantly higher in rural areas compared to the urbans (3.91 vs. 3.40; P value=0.04). In the last 13 years, rural population had a significant increasing trend in ASIR of LC (average annual percent change [AAPC]=7.85, P value=0.005). LC was more prevalent in men among both urban and rural populations. The results showed a significant increasing trend in rural areas that requires Golestan health care system to take action in controlling the burden of LC in rural areas.

Immune Checkpoint Therapy for Hepatocellular Carcinoma

Globally, chronic hepatitis B virus (HBV) infection is now caused about 60% of the liver cancer. In China, more than 90% of liver cancers are caused by HBV infection. Approximately 800,000 new cases of liver cancer are reported worldwide every year, and the overall prognosis is lack than normal. Most patients with liver cancer suffer from liver diseases such as hepatitis, liver cirrhosis, and abnormal liver function, which cause the onset of liver cancer to be hidden and progress rapidly. The diagnosis is the middle and late stage, and the best opportunity for surgery and other local treatments is lost. The Global Hepatitis Report 2017 released by the World Health Organization shows that more than 325 million people are infected with hepatitis B or C worldwide, and about 1.34 million people die each year. In China, there are about 90 million people with chronic hepatitis B virus, 30 million patients with chronic hepatitis B, and only 2 million people receive treatment, which is less than 1/10 of the total. How to improve the standardized diagnosis and treatment level of liver cancer and optimize the diagnosis and treatment strategy has always been a concern. The liver cancer drug develop is dominated by antibody drugs, of which PD-1/PD-L1 and CTLA-4 are the primary goal of antibody development. The research and development of chemical drugs takes VEGFR and BRAF proteins as the main research targets. At the same time, PD-1 and related drugs that have been on the market have shown good curative effects in a variety of tumor treatments.