Liver Cancer Screening Research Articles

Overexpression of TCERG1 as a prognostic marker in hepatocellular carcinoma: A TCGA data-based analysis.

Objective: Transcription elongation factor 1 (TCERG1) is a nuclear protein consisted of multiple protein structural domains that plays an important role in regulating the transcription, extension, and splicing regulation of RNA polymerase II. However, the prognostic and immunological role of TCERG1 in human cancer remains unknown. In this study, we analyzed the expression of TCERG1 gene in hepatocellular carcinoma (HCC) patients, its clinical significance, and its possible prognostic value by bioinformatics. Methods: RNA sequencing data and clinicopathological characteristics of patients with HCC were collected from TCGA and CCLE databases. The Wilcoxon rank-sum test was used to analyze the expression of TCERG1 in HCC tissues and normal tissues. The protein levels of TCERG1 between normal and liver cancer tissues were analyzed by the Human Protein Atlas Database (HPA) (www.proteinatlas.org). Validation was performed using the Gene Expression Omnibus (GEO) dataset of 167 samples. The expression of TCERG1 in HCC cells were verified by qRT-PCR, and CCK-8, scratch assay and Transwell assay were performed to detect cell proliferation, migration and invasion ability. According to the median value of TCERG1 expression, patients were divided into high and low subgroups. Logistic regression, GSEA enrichment, TME, and single-sample set gene enrichment analysis (ssGSEA) were performed to explore the effects of TCERG1 on liver cancer biological function and immune infiltrates. TCERG1 co-expression networks were studied through the CCLE database and the LinkedOmics database to analyze genes that interact with TCERG1. Results: The expression levels of TCERG1 in HCC patient tissues were significantly higher than in normal tissues. Survival analysis showed that high levels of TCERG1 expression were significantly associated with low survival rates in HCC patients. Multifactorial analysis showed that high TCERG1 expression was an independent risk factor affecting tumor prognosis. This result was also verified in the GEO database. Cellular experiments demonstrated that cell proliferation, migration and invasion were inhibited after silencing of TCERG1 gene expression. Co-expression analysis revealed that CPSF6 and MAML1 expression were positively correlated with TCERG1. GSEA showed that in samples with high TCERG1 expression, relevant signaling pathways associated with cell cycle, apoptosis, pathways in cancer and enriched in known tumors included Wnt signaling pathway, Vegf signaling pathway, Notch signaling pathway, MAPK signaling pathway and MTOR pathways. The expression of TCERG1 was positively correlated with tumor immune infiltrating cells (T helper two cells, T helper cells). Conclusion: TCERG1 gene is highly expressed in hepatocellular carcinoma tissues, which is associated with the poor prognosis of liver cancer, and may be one of the markers for the diagnosis and screening of liver cancer and the prediction of prognosis effect. At the same time, TCERG1 may also become a new target for tumor immunotherapy.

Development and validation of a risk prediction model for incident liver cancer.

We aimed to develop and validate a risk prediction model for liver cancer based on routinely available risk factors using the data from UK Biobank prospective cohort study. This analysis included 359,489 participants (2,894,807 person-years) without a previous diagnosis of cancer. We used the Fine-Gray regression model to predict the incident risk of liver cancer, accounting for the competing risk of all-cause death. Model discrimination and calibration were validated internally. Decision curve analysis was conducted to quantify the clinical utility of the model. Nomogram was built based on regression coefficients. Good discrimination performance of the model was observed in both development and validation datasets, with an area under the curve (95% confidence interval) for 5-year risk of 0.782 (0.748-0.816) and 0.771 (0.702-0.840) respectively. The calibration showed fine agreement between observed and predicted risks. The model yielded higher positive net benefits in the decision curve analysis than considering either all participants as being at high or low risk, which indicated good clinical utility. A new risk prediction model for liver cancer composed of routinely available risk factors was developed. The model had good discrimination, calibration and clinical utility, which may help with the screening and management of liver cancer for general population in the public health field.

Risk stratification of primary liver cancer.

The risk stratification of primary liver cancer (PLC) discussed in a review of viral hepatitis and PLC could lead to misunderstandings by readers. For example, a single study or a small number of studies cannot comprehensively summarize the risk factors of PLC, is not included in the family history of liver cancer, and chronic hepatitis D is listed as a medium risk factor for the development of PLC. Currently, PLC prediction models with good clinical validation values have been applied clinically, such as the Toronto hepatocellular carcinoma risk index, REACH-B model, and PAGE-B model. Therefore, the Chinese, together with several research societies, have formulated the “Guideline for stratified screening and surveillance of primary liver cancer (2020 edition).” This guideline outlines PLC screening in at-risk populations, both in hospitals and communities. It is recommended to stratify the at-risk population into four risk levels: low-, intermediate-, high-, and extremely high-risk. This is highly recommended and applied in clinical practice.

Salivary orosomucoid 1 as a biomarker of hepatitis B associated hepatocellular carcinoma

Saliva is rich in proteins, DNA, RNA and microorganisms, and can be regarded as a biomarker library. In order to explore a noninvasive and simple means of early screening for liver cancer, proteomics was used to screen salivary markers of hepatitis B associated liver cancer. We used mass spectrometry coupled isobaric tags for relative and absolute quantitation (iTRAQ)-technology to identify differentially expressed proteins (DEPs). Western blot, immunohistochemistry and enzyme linked immunosorbent assay were used to detect marker expression of in tissues and saliva. Statistical analysis was used to analyze the diagnostic efficacy of the markers was analyzed through statistical analyses. By comparing the hepatocellular carcinoma (HCC) group with non-HCC groups, we screened out 152 salivary DEPs. We found orosomucoid 1(ORM1) had significantly higher expression in saliva of HCC patients compared with non-HCC groups (p < 0.001) and the expression of ORM1 in liver cancer tissues was significantly higher than that in adjacent normal tissues (p < 0.001). The combination of salivary ORM1 and alpha-fetoprotein (AFP) showed reasonable specificities and sensitivities for detecting HCC. In a word, salivary ORM1 as a new biomarker of hepatitis B associated hepatocellular carcinoma, combination of salivary ORM1 and AFP as an improved diagnostic tool for hepatocellular carcinoma.

Construction and application of liver cancer models in vitro

• The current methods or techniques for preparing 3D in vitro liver cancer models were introduced. • The relevant applications of 3D in vitro liver cancer models were summarized. • The advantages and disadvantages of 3D in vitro liver cancer models were discussed. • This review proposed future prospects and research directions of 3D in vitro liver cancer models. Primary liver cancer is the fifth most common malignancy and the third leading cause of cancer death worldwide. Although current advances in the treatment of liver cancer, the prognosis of this cancer remains unfavorable. Appropriate liver cancer model in vitro is an important way to study the pathogenesis and drug screening of liver cancer. This review provides a comprehensive summary and discussion on the construction and application of liver cancer models in vitro, in particular hepatocellular carcinoma (HCC). Specifically, after introducing the current methods or techniques for preparing 3D in vitro liver cancer models, this review summarizes the relevant applications of these liver cancer models in vitro, e.g. drug screening, personalized medicine, and other applications. In the end, this review discusses the advantages and disadvantages of the liver cancer models in vitro, and proposes future prospects and research directions. Schematic diagram Construction and application of liver cancer models in vitro.

Assessment of the compliance, influencing factors, and yielding results of liver cancer screening in a high-risk population: A cross-sectional study.

The participation and results for liver cancer screening are rarely reported. The aim of this study was to determine the participation rates and factors affecting participation rates as well as to report the detection rate for liver cancer in an organized screening program. The organized screening program for liver cancer was conducted in 12 rural sites. The risk of developing liver cancer was initially evaluated for each participant. High-risk individuals were offered α-fetoprotein measurement and ultrasonography examination. Potential risk factors associated with the participation rate were screened by fitted generalized linear mixed logistic regression models through reporting odds ratios (ORs) with 95% CIs. A total of 358,662 eligible participants completed the basic surveys, and 54,745 were evaluated to be at high risk of liver cancer. Of these high-risk individuals, 40,543 accepted the screening services. Determinants of participation for screening behavior included older age, being female, being positive for hepatitis B surface antigen, having a family history of liver cancer, chronic depression, and low income. The detection rate for liver cancer was estimated to be 0.41% (95% CI, 0.35-0.48). This study reported several significant factors associated with the screening behaviors for liver cancer. Participation rate and results for liver cancer screening in rural areas are rarely reported. The determinants associated with adherence rates and early detection rate of liver cancer in an organized screening program for liver cancer were assessed. A possible positive correlation between the participation rates and the early detection rate was observed among attendees of screening. These new finds could be beneficial to increasing the participation rate of screening.

Multi-omics research contributes to early screening, diagnosis and treatment of liver cancer

In 2016, the World Health Organization set an ambitious goal of reducing viral hepatitis-related deaths by 65% by 2030. The key to this goal is to reduce viral hepatitis-related HCC deaths. Liver cancer is the fourth most common malignant tumor and the second leading cause of cancer death in China. The onset of HCC is insidious, and most patients are already in the middle and late stage when diagnosed. Despite the great progress on management of HCC, the therapeutic effect and prognosis of HCC are still unsatisfactory. Therefore, multi-dimensional and comprehensive analysis of the mechanism of liver cancer, improving the early screening, diagnosis and treatment rate of liver cancer are the key points of reducing the harm of liver cancer in China. In recent years, multi-omics studies have been widely applied in the field of liver cancer, providing a basis for the pathogenesis of liver cancer, early detection and diagnosis, development of individual treatment strategies and prognosis assessment. This issue will focus on the application of genomics, proteomics, metabolomics and imaging omics in early screening, diagnosis and treatment of liver cancer.

China guideline for liver cancer screening (2022, Beijing)

China guideline for liver cancer screening (2022, Beijing)

Development and Validation of a Noninvasive Risk Score Model for Liver Cirrhosis in At-Risk Alcohol Drinkers Without HBV/HCV Infection.

The risk model we developed will not only be used as a practical tool to triage high risk groups for liver cirrhosis, but also have implications for public health measures, such as guidelines for the prevention of liver cancer, in at-risk alcohol drinkers without HBV/HCV infection.

Access to liver cancer screening and surveillance in populations in China: an exploratory analysis

Objective: To systematically quantify the access to screening and surveillance service of liver cancer in populations in China, especially a series of sub-indicators of the availability. Methods: Following the specific indicators applied by the International Agency for Research on Cancer in the session of availability and use of screening practices in several cancer screening handbooks, information about the access/availability of liver cancer screening and surveillance in population in China were collected; the indicators included local policies and guidelines, procedures most commonly used or recommended, population coverage and participation rate, compliance and related factors, treatment rate, acceptability, equity and others. Systematic review approach was used, combined with searching core literatures/monograph, websites of governments and available program reports, for a systematic analysis on the access to liver cancer screening and surveillance in populations in China. Results: A total of 34 journal articles were included from the systematic review and most of which were about the participation of secondary liver screening or surveillance compliance; additional information were mainly obtained from the other sources. Overall, there were clearly recommended screening and surveillance procedures for liver cancer in the three major cancer screening programs funded by the central government of China. It was estimated that 0.09% of the population aged 35-74 years were covered by liver cancer screening in 2019 in China. The overall participation rates of secondary screening ranged from 37.5% to 62.3% in three major programs, the median compliance rate of surveillance was reported as 26.9% (Q1,Q3: 23.5%, 41.0%) in the 6 included studies. Two studies reported the factors affecting the participation and compliance. A large-scale multicenter analysis showed that the subject acceptability to alpha fetoprotein test combined with ultrasound screening was as high as 99.3% in high-risk population in urban area. The treatment rate of liver cancer founded by screening, surveillance or follow-up was estimated to be >90% in rural population. No studies of equity were obtained via the systematic review. Conclusions: The public health service programs in China all recommend specific procedures for liver cancer screening in general population and surveillance for high-risk individuals. However, the overall availability needs to be improved, particularly in the indicator of population coverage. Participation rates of screening and compliance rates of surveillance varied among the included programs and the studies, suggesting that the influencing factors need to be further identified. The relatively high subject acceptability suggests the potential demands for screening service. More efforts are needed to address the access to screening and surveillance of liver cancer in populations in China.

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease.

This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56). HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

MRI in liver cirrhosis

AbstractLiver magnetic resonance imaging (MRI) has seen a massive increase in its use over the last decades. Since its first description in the early 1980s, contrast‐enhanced MRI is now the gold standard for the diagnosis of hepatocellular cancer in patients with liver cirrhosis. Techniques like magnetic resonance (MR) elastography and combinations of multiple MR parameters in single scanning protocols are now available and these are opening new possibilities for the assessment of multiple aspects of disease in patients with liver cirrhosis. In this narrative review, we provide an overview of the use of MRI in patients with cirrhosis for the diagnosis of and screening for liver cancer, for the diagnosis of cirrhosis and prediction of long‐term outcomes, and for the evaluation of portal hypertension. With the multitude of techniques now available and the number of cirrhosis aspects that can be assessed by single scans make the study and application of MRI an attractive target in the search for a technique for use in this group of patients that often have to attend for multiple appointments and multiple tests, including invasive investigations.

Multimodal Treatment of Hepatocellular Carcinoma in Patients With Hepatitis C Virus Infection Treated With Direct-Acting Antivirals.

Background: Direct-acting antivirals (DAAs) opened a new era in the management of hepatitis C virus (HCV)-associated liver disease. However, hepatic cancer screening should not be stopped after obtaining a sustained virologic response (SVR). Current guidelines offer several treatment options for hepatocellular carcinoma (HCC), mainly depending on its stage and the extent of liver disease, including tumor resection, liver transplantation (LT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and systemic agents. This article provides an overview of treatment modalities for hepatocellular carcinoma and associated survival rates based on the experience of the Internal Medicine Center at Fundeni Clinical Institute while bringing into light previous medical research.Methods: We included 59 patients with a personal history of hepatitis C virus infection, diagnosed with hepatocellular carcinoma at least one year after achieving a sustained virologic response through direct-acting antivirals. The albumin-bilirubin (ALBI) score and Barcelona Clinic Liver Cancer (BCLC) classification were assessed in each case, and all patients were treated accordingly. The subjects were monitored by liver function tests, tumor markers, blood cell count, coagulation profile, and imaging explorations. We investigated the Eastern Cooperative Oncology Group (ECOG) performance status, the response to applied treatments, and survival.Results: Cirrhotic patients and multinodular tumor patterns were predominant. Most patients only experienced one therapeutic procedure, while the rest of the study group went through multiple treatment modalities (2-4), with a better outcome in terms of survival parameters. A large proportion presented with disease progression despite the therapeutic measures applied. A total of two liver transplants were performed, resulting in a 12-month disease-free period among these patients. The presence of diabetes mellitus (DM), multinodular disease, alpha-fetoprotein (AFP) over 300 ng/mL, and tumor dimension over 6 cm indicate poor overall survival. Both overall survival and progression-free survival were better in subjects who presented complete responses (CR) to HCC treatment. In patients undergoing a single intervention, the best overall survival was associated with surgical resection and RFA.Conclusion: The multimodal treatment of hepatocellular carcinoma represents the best approach, in order to maintain patients on the waiting list for liver transplantation. In hepatitis C virus infection, viral clearance is important to obtain. At the same time, particular attention should be paid to liver cancer screening even after obtaining a sustained virologic response.

Global pattern of trends in incidence, mortality, and mortality-to-incidence ratio rates related to liver cancer, 1990–2019: a longitudinal analysis based on the global burden of disease study

BackgroundLiver cancer (LC) is considered as one of the most dominant malignant tumors which ranked 4th and 6th in terms of global mortality and incidence, respectively. This work aimed to investigate the global temporal trends in LC mortality-to-incidence ratio (MIR) and its components, with a particular focus on examining long-term effect of human development index (HDI) on these metrics in a 30-year follow-up.MethodsThe age-standardized LC incidence and mortality data were derived from the global burden of disease (GBD) study 2019. We first leveraged joinpoint piecewise linear regression analysis to ascertain time trends in LC incidence, mortality, and MIR complement [1-MIR] and the average annual percentage change (AAPC) of the rates over the period 1990–2019. Then, the association between the metrics and HDI was explored through longitudinal multilevel models (LMMs).ResultsThe incidence rates paralleled the mortality rates worldwide and they had similar significant monotonic decrementing trends with AAPC values of − 1.10% (95% confidence interval (CI): − 1.40, − 0.90%) and − 1.40% (− 1.50, − 1.30%), respectively from 1990 to 2019. The [1-MIR] rates were around 0 and showed an increasing pattern from 1.70 to 8.10 per 100,000 people (AAPC, 4.90%) at the same period of time. Results from the LMMs displayed that the majority of the variation lies at the country level accounted for about 88% of the total variance. Moreover, our analysis supported that the HDI was negatively associated with either incidence or mortality over time (p < 0.05).ConclusionsOur findings highlighted that the global long-term temporal trends of LC incidence and mortality decreased slightly during 1990–2019 which may reflect improved therapeutic strategies and public health interventions. Besides, the low rates of [1-MIR] revealed the five-year relative survival rate was poor implying LC is diagnosed late in its development. Thereby, the policymakers’ focus must be on early screening and detection of liver cancer.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication

Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

The Effect of Social Norms on Physicians' Intentions to Use Liver Cancer Screening: A Cross-Sectional Study Using Extended Theory of Planned Behavior.

BackgroundLiver cancer is a globally acknowledged threat to public health, and there is a critical and urgent need to determine factors associated with the use of liver cancer screening and to further promote its use.PurposeTo examine whether the extended theory of planned behavior (TPB) incorporating social norms predicts physicians’ intentions to use liver cancer screening and to identify the associated factors quantitatively, using contrast-enhanced ultrasound (CEUS) as an example.MethodsA research framework was established by adding social norms to the TPB, based on which the questionnaire for this study was developed. Through multistage random sampling, a cross-sectional questionnaire survey was conducted among 292 physicians in Fujian and Jiangxi provinces. Due to the multicollinearity problem of the data, ridge regression was applied to determine the influencing factors of physicians’ intentions to use CEUS.ResultsMost participants (87.30%) reported that they were willing to use liver cancer screening in their clinical practice. The scores of TPB variables were generally higher than those of social norms variables. Ridge regression results indicated that the proposed model was explanatory, which has accounted for 73.5% of the total variance in physicians’ intentions. Analyses also illustrated the significant role of TPB variables (attitude and perceived behavioral control) and social norms variables (personal norms, organizational norms, and industrial norms) on physicians’ intentions to use CEUS.ConclusionThe study extended the TPB by including the concepts of social norms, which is not only conducive to expanding the knowledge of factors associated with physicians’ intentions to use liver cancer screening, but also provides implications for developing strategies to promote the use of certain health services or products, such as playing the role of core members, holding panel meetings, and establishing information push systems.

AI-DRIVEN Novel Approach for Liver Cancer Screening and Prediction Using Cascaded Fully Convolutional Neural Network.

In experimental analysis and computer-aided design sustain scheme, segmentation of cell liver and hepatic lesions by an automated method is a significant step for studying the biomarkers characteristics in experimental analysis and computer-aided design sustain scheme. Patient to patient, the change in lesion type is dependent on the size, imaging equipment (such as the setting dissimilarity approach), and timing of the lesion, all of which are different. With practical approaches, it is difficult to determine the stages of liver cancer based on the segmentation of lesion patterns. Based on the training accuracy rate, the present algorithm confronts a number of obstacles in some domains. The suggested work proposes a system for automatically detecting liver tumours and lesions in magnetic resonance imaging of the abdomen pictures by using 3D affine invariant and shape parameterization approaches, as well as the results of this study. This point-to-point parameterization addresses the frequent issues associated with concave surfaces by establishing a standard model level for the organ's surface throughout the modelling process. Initially, the geodesic active contour analysis approach is used to separate the liver area from the rest of the body. The proposal is as follows: It is possible to minimise the error rate during the training operations, which are carried out using Cascaded Fully Convolutional Neural Networks (CFCNs) using the input of the segmented tumour area. Liver segmentation may help to reduce the error rate during the training procedures. The stage analysis of the data sets, which are comprised of training and testing pictures, is used to get the findings and validate their validity. The accuracy attained by the Cascaded Fully Convolutional Neural Network (CFCN) for the liver tumour analysis is 94.21 percent, with a calculation time of less than 90 seconds per volume for the liver tumour analysis. The results of the trials show that the total accuracy rate of the training and testing procedure is 93.85 percent in the various volumes of 3DIRCAD datasets tested.

Gut microbiome alteration as a diagnostic tool and associated with inflammatory response marker in primary liver cancer.

Primary liver cancer has high mortality and morbidity worldwide. However, the characteristic of gut microbiota profile and its correlation with inflammation status in liver cancer patients remains largely unknown, and a gut microbiome-based diagnostic model for liver cancer is still absent. Here, we provided a comprehensive analysis based on fecal 16S rRNA sequencing and clinical data in a cohort consisting of 40 healthy volunteers, 143 hepatocellular carcinoma (HCC) patients, and 46 cholangiocarcinoma (CCA) patients. Our results indicated a distinct shift of gut microbiota composition between two primary liver cancer types and compared with healthy volunteers. Based on the diversity constitute of gut microbiome taxonomy and random forest algorithm, eight genera with mean abundance above 0.1% were selected to construct the classification model with half of the randomly selected cohort. Based on this signature, high diagnostic accuracy in the validation cohort to classify liver cancer types (AUC = 0.989, 0.967, 0.920 for Control, HCC, CCA separately) was achieved. Further analysis showed increased Gram-negative bacteria and elevated inflammatory response markers in CCA group versus HCC group. The correlation analysis between inflammatory response markers and composition of gut microbiome revealed decreased potentially beneficial genus and increased opportunistic pathogens positively correlated with adverse prognostic inflammatory response markers. Generally, our study established the gut microbiome-based signature for liver cancer prediction and screening and revealed that gut microbiome characteristic in primary liver cancer was correlated with adverse inflammatory response markers in liver cancer.

Abstract PO-058: Increasing liver cancer prevention knowledge through a community-based education initiative to improve liver cancer prevention for underserved African, Asian, and Hispanic communities

Abstract Background: Though a largely preventable disease, liver cancer is now the fastest-increasing cause of cancer death in the US, and it is highly fatal. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, and it disproportionally affect racial/ethnic minorities, especially the medically underserved. Most HCC cases are associated with hepatitis B virus (HBV) and hepatitis C virus (HCV). Methods: To increase awareness of liver cancer prevention and screening, we partnered with community-based organizations through NCI funded U54 TUFCCC/HC Cancer Partnership Community Outreach Core, in the greater Philadelphia metropolitan and New York City to design and conduct a liver cancer prevention project. Pre- and post- survey data was collected from underserved Asian, African, and Hispanic American community members who participated in educational workshops. This abstract will report the 473 eligible participants' knowledge on HBV, HCV, and liver cancer both before and after the education. We conducted wilcoxon Signed-rank, Kruskal-Wallis, and Wilcoxon sum-rank tests. Results: Knowledge of risk factors increased significantly in all three communities from the pre-survey to the post-intervention survey (2.15 vs. 3.69, p&amp;lt;0.0001). Knowledge of risk factors also significantly increased within the African (1.11, p&amp;lt;0.0001), Asian (1.88, p&amp;lt;0.0001) and Hispanic (3.21, p&amp;lt;0.0001) American Communities. There were no significant differences in increased knowledge by gender (male= 2.18 vs female=2.25, p=0.72). Conclusions: The findings of our study show the importance and effectiveness educational interventions have on promoting liver cancer prevention knowledge among the minority groups who are most affected in the U.S. by liver cancer disparity. Citation Format: Wenyue Lu, Lin Zhu, Safa Ibrahim, Kerry Traub, Ellen Kim, Ada Wong, Nathaly Rubio-Torio, Evelyn Gonzalez, Marilyn A. Fraser, Ming-Chin Yeh, Grace X. Ma, Olorunseun O. Ogunwobi, Yin Tan. Increasing liver cancer prevention knowledge through a community-based education initiative to improve liver cancer prevention for underserved African, Asian, and Hispanic communities [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-058.

NMDA receptor expression during cell transformation process at early stages of liver cancer in rodent models.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, which is not sensitive to radiotherapy and chemotherapy and very often experiences postoperative relapse. In this regard, effective screening of liver cancer is considered as the most important and urgent task. The aim of our study was to determine whether N-methyl-D-aspartate receptor (NMDAR) and, in particular, its subunits, can serve as biomarkers to distinguish the precancerous liver at early stages of liver fibrosis. We assessed the development of HCC after 10, 15, and 22 wk using a HCC rat model. The expression of NMDAR subunits was monitored at different stages of HCC by means of immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting, and direct bisulfite sequencing. NMDAR subunits were not found in healthy liver tissues. In contrast, NMDAR subunits, in particular NR1 and NR2B, appeared at the stage of severe liver fibrosis (precancerous liver disease) in rats and were expressed during the development of HCC in rats and mice. Using the direct bisulfite sequencing, we detected that increased expression of NMDAR directly correlated with the demethylation of CpG islands in the promoter region of genes encoding receptor subunits. The obtained results confirmed that NMDAR subunits can serve as new biomarkers of precancerous liver disease, severe fibrosis, and its progression towards HCC.NEW & NOTEWORTHY We have shown NMDAR expression in cell transformation process at early stages of cancer, specifically HCC. The aim of our study was to define the disease stages from precancerous liver disease towards liver cancer progression when NMDAR subunits were expressed/detected. A fibrosis/HCC rat model, immunohistochemistry combined with epifluorescence microscopy imaging, Western blotting was used. The dynamics of appearance of NMDAR subunits, their expression and methylation status during the development of HCC were shown and discussed.