Survival Rate Of Hepatocellular Carcinoma Research Articles

Abstract 717: Racial and ethnic disparities in presentations and survival rates of hepatocellular carcinoma

Abstract Background: Liver cancer is one of the leading causes of malignant tumor deaths worldwide and Hepatocellular Carcinoma (HCC) accounts for approximately 90% of all liver cancer cases. Methods:We examined data from the Surveillance, Epidemiology and End Results (SEER)Medicare database to identify patients diagnosed with primary HCC between 2004 and 2017.. Demographics such as race, age of diagnosis, and clinical information, such as the survival status also were collected. The disease specific and relative five year survival rates and 95% confidence intervals were also calculated. Results:Among the 79819 patients selected, 55,484 (69.5 %) of them were White, 9,956 (12.5%) were Black, 1,158 (1.4%) were American Indian/Alaska Native, and 13211 (16.6%) were Asian or Pacific Islander. The incident trends indicated that incidence had been gradually increased for white, black, and American Indian/Alaska Natives with near identical slopes until they flattened into a plateau in 2014 or 2015 (61.8 per million to 96.9 per million for White with a P>0.05, and 93.9 per million to 135.1 per million for Black with a P>0.05). After 2014/2015 the incidences slightly decreased for both White and Black without being statistically significant (P>0.05). The pattern for the American Indian/Alaska Native population was also similar without statistical significance (P>0.05), possibly due to the sample size. Although HCC incidence among the Asian or Pacific Islander populations were much higher than other races in 2004, it steadily decreased during the observation period,from 188.7 per million to 142.5 per million, which was close to the incidences of other races. Age disparity in HCC diagnosis also existed. For example, in the Asian or Pacific Islander HCC patients, 38.2% were patients older than 70. Whereas, this number was 16.8% in Black patients.Our research also indicated that the Asian or Pacific Islander category had the highest HCC five year cause specific survival rate (32.0% with 95% CI 31.0% to 32.9%) and also the highest five year relative survival rate (27.8% with 95% CI 26.9% to 28.7%), followed by White (24.0% with 95% CI 23.6% to 24.5% and 19.9% with 95% CI 19.5% to 20.3% respectively), American Indian/Alaskan Native (21.5% with 95% CI 18.6% to 24.5% and 16.0% with 95% CI 13.6% to 18.5%% respectively), and Black (20.9% with 95% CI 19.9% to 21.9% and 16.6 with 95% CI 15.7% to 17.5% respectively). The statistical significance could be observed as early as the 6 month follow-up. Conclusion:From 2004 to 2017, the HCC incidence steadily decreased for the Asian or Pacific Islander category, but not for other races. Now, with more advanced treatments being available, Asian or Pacific Islander HCC patients also have the highest five year survival rates. American Indian/Alaskan Native and Black have the lowest five year survival rates. The HCC racial and ethnic disparities still exist after two decades since we launched Healthy People 2000. Citation Format: Jingwei Song, Eric Song, Daniel Gharavi. Racial and ethnic disparities in presentations and survival rates of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 717.

Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Is a Promising Signature to Predict Prognosis and Therapies for Hepatocellular Carcinoma (HCC)

The roles of mitochondria and the endoplasmic reticulum (ER) in the progression of hepatocellular carcinoma (HCC) are well established. However, a special domain that regulates the close contact between the ER and mitochondria, known as the mitochondria-associated endoplasmic reticulum membrane (MAM), has not yet been investigated in detail in HCC. The TCGA-LIHC dataset was only used as a training set. In addition, the ICGC and several GEO datasets were used for validation. Consensus clustering was applied to test the prognostic value of the MAM-associated genes. Then, the MAM score was constructed using the lasso algorithm. In addition, uncertainty of clustering in single-cell RNA-seq data using a gene co-expression network (AUCell) was used for the detection of the MAM scores in various cell types. Then, CellChat analysis was applied for comparing the interaction strength between the different MAM score groups. Further, the tumor microenvironment score (TME score) was calculated to compare the prognostic values, the correlation with the other HCC subtypes, tumor immune infiltration landscape, genomic mutations, and copy number variations (CNV) of different subgroups. Finally, the response to immune therapy and sensitivity to chemotherapy were also determined. First, it was observed that the MAM-associated genes could differentiate the survival rates of HCC. Then, the MAM score was constructed and validated using the TCGA and ICGC datasets, respectively. The AUCell analysis indicated that the MAM score was higher in the malignant cells. In addition, enrichment analysis demonstrated that malignant cells with a high MAM score were positively correlated with energy metabolism pathways. Furthermore, the CellChat analysis indicated that the interaction strength was reinforced between the high-MAM-score malignant cells and T cells. Finally, the TME score was constructed, which demonstrated that the HCC patients with high MAM scores/low TME scores tend to have a worse prognosis and high frequency of genomic mutations, while those with low MAM scores/high TME scores were more likely to have a better response to immune therapy. MAM score is a promising index for determining the need for chemotherapy, which reflects the energy metabolic pathways. A combination of the MAM score and TME score could be a better indicator to predict prognosis and response to immune therapy.

How Biology Guides the Combination of Locoregional Interventional Therapies and Immunotherapy for Hepatocellular Carcinoma: Cytokines and Their Roles.

As most patients with hepatocellular carcinoma (HCC) are diagnosed at the intermediate or advanced stage and are no longer eligible for curative treatment, the overall survival rate of HCC remains unsatisfactory. Locoregional interventional therapies (LITs), and immune checkpoint inhibitor (ICI)-based immunotherapy, focus on treating HCC, but the efficacy of their individual application is limited. Therefore, the purpose of this review was to discuss the biological roles of cytokines and their therapeutic potential in the combination therapy of LITs and ICI-based immunotherapy. The two common techniques of LITs are ablative and transarterial therapies. Whether LITs are complete or incomplete can largely affect the antitumor immune response and tumor progression. Cytokines that induce both local and systemic responses to LITs, including interferons, interleukins, chemokines, TNF-α, TGF-β, VEGF, and HGF, and their roles are discussed in detail. In addition, specific cytokines that can be used as therapeutic targets to reduce immune-related adverse events (irAEs) are introduced. Overall, incomplete LITs in a tumor, combined with specific cytokines, are thought to be effective at improving the therapeutic efficacy and reducing treatment-induced irAEs, and represent a new hope for managing unresectable HCC.

A novel nomogram to predict survival of patients with hepatocellular carcinoma after transarterial chemoembolization: a tool for retreatment decision making.

There is still no standardized policy regarding how to identify patients who are not benefiting from transarterial chemoembolization (TACE). We aimed to establish and validate a nomogram model to predict the survival rate of hepatocellular carcinoma (HCC) patients after TACE. A total of 578 HCC patients undergoing initial TACE at the First Affiliated Hospital of Wenzhou Medical University were retrospectively recruited to the study. The patients were randomly divided into 2 cohorts: a training cohort (n=405) and a validation cohort (n=173). To develop the nomogram, Cox regression analyses were used to identify independent risk factors. The performances of the nomogram were assessed by concordance index (C-index), calibration curves, and decision curve analysis (DCA), and were compared to 4 developed prognostic models. We used 5 independent risk factors including postoperative albumin-bilirubin (ALBI) grade, tumor diameter, number of tumors, portal vein invasion, and tumor response to develop the nomogram. Calibration curves showed consistency between the nomogram and the actual observation. The C-index of the nomogram was 0.753 [95% confidence interval (CI): 0.722, 0.784], which was higher than the other prognostic models (P<0.001). The DCA showed that the nomogram had the highest net benefit among the models. According to predicted survival risk, the nomogram could divide patients into 3 groups (P<0.001). All the results were verified in the validation cohort. This study developed and validated a nomogram model for HCC patients undergoing TACE, which could predict the survival rate and provide support for further treatment strategies.

Overexpression of SMS in the tumor microenvironment is associated with immunosuppression in hepatocellular carcinoma.

Disorders of polyamine metabolism may contribute to the development of hepatocellular carcinoma (HCC), but the precise mechanism remains unknown. This study reports that spermine synthase (SMS), an enzyme involved in polyamine biosynthesis, is overexpressed in HCC and not associated with hepatitis virus infection in HCC patients. The results of analyzing the clinical data of HCC patients showed that SMS level as a categorical dependent variable was related to clinicopathological features of poor prognosis. Furthermore, the Kaplan-Meier survival analysis and ROC curve indicated that increased SMS level is associated with poor survival rate in HCC and may be a potential biomarker to discriminate HCC tissues. However, SMS overexpression limited the therapeutic effect of immune checkpoint blockade (ICB), which seemed to be related to the immunosuppressive effect of the HCC immune microenvironment formed by higher mRNA transcript levels of immune checkpoints and higher infiltration levels of immunosuppressive cells. In samples with high and low SMS expression, functional enrichment analysis of the differentially expressed genes (DEGs) showed that SMS may be linked to the occurrence and development of HCC by affecting a variety of immune-related pathways, such as Intestinal immune network for IgA production, Fc gamma R-mediated phagocytosis, Antigen processing and presentation, Th1 and Th2 cell differentiation. Subsequently, analysis of the co-expression network of SMS in the liver hepatocellular carcinoma (LIHC) cohort revealed that SMS has a broad impact on multiple important immune- and metabolic-related processes in HCC. In summary, SMS is a promising biomarker to differentiate the prognosis, immune characteristics, and holds promise as a potential target for ICB therapy to improve HCC.

Increased Expression of NXPH4 Correlates with Immune Cell Infiltration and Unfavorable Prognosis in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading malignant carcinomas. Despite the advancement in the treatment for HCC, such as precise hepatectomy, radiotherapy, transarterial therapies, chemotherapy, targeted treatments, and immunotherapy, the 5-year overall survival rate of HCC is extremely low. Hence, novel biomarkers are urgently needed for advancing the therapy and prognosis of HCC. Neurexophilin 4 (NXPH4) is a neuropeptide-like glycoprotein. The study is designed to investigate the function of NXPH4 in HCC through a comprehensive bioinformatics analysis. NXPH4 expression status and prognostic values were analyzed via multiple datasets, such as TCGA, GEO, and ICGC. The association between NXPH4 and immune cell infiltration was estimated by TIMER, TISIDB, and CIBERSORT. In vitro, we explored the biological function of NXPH4 in JHH7 and SNU182 cells through knocking down the expression of NXPH4 via siRNA. In general, NXPH4 was predominantly upregulated in HCC tumors, and increased NXPH4 expression predicted unfavorable prognosis. The gene enrichment analysis displayed that NXPH4 was related with metabolic pathways. NXPH4 expression was correlated with immune cell infiltration. NXPH4 knockdown significantly suppressed proliferation, migration, and invasion of JHH7 and SNU182 cells. This study suggested that the upregulation of NXPH4 is associated with adverse prognosis and immune cell infiltration in HCC. NXPH4 could be a novel biomarker of unfavorable prognosis and an underlying target for immunotherapy in HCC.

S1389 The Impact of Race on the Overall Survival Rate of Hepatocellular Carcinoma in the African-American Population

Introduction: Hepatocellular carcinoma (HCC) accounts for approximately 90% of the incidence of all primary liver cancers. It is also the fifth most prevalent malignancy worldwide and the fourth global leading cause of death. Previous U.S.-based studies on survival rates suggest ethnic disparities among HCC patients; however, this is incompletely understood due to a variety of risk factors. Notable risk factors include oncogenic viral infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), alcohol abuse, and metabolic syndrome secondary to obesity and diabetes mellitus. This study aims to investigate whether race plays a role in the overall survival rate of hepatocellular carcinoma. Methods: Using the cBioPortal platform and systematic bioinformatical-analysis of The Cancer Genome Atlas (TCGA) PanCancer Atlas dataset, we analyzed the effect of race on overall survival rate. The study included 360 HCC patients (234 living patients and 126 deceased patients). The following races were included: White, Black or African American, and Asian. Results: The impact of race on the overall survival rate of hepatocellular carcinoma was statistically significant (p < 0.0206) and appeared to be higher in the African American group (64.71%) compared to the White (57.92%). Of note, the Asian group had the highest overall survival rate (73.13%). (Figure) Conclusion: The findings in this study suggest that race may play a role in the risk of developing hepatocellular carcinoma and potential treatment options. Further studies are warranted to evaluate the genetic alterations in various race groups.Figure 1.: Hepatocellular carcinoma overall survival among the African American, White, and Asian populations.

H2AFX might be a prognostic biomarker for hepatocellular carcinoma.

H2AFX can play a central role in DNA repair, replication, transcription regulation, and chromosomal stability. However, there is little research to explore the expression of H2AFX in cancers. Moreover, the correlation between the expression of H2AFX and tumor immunity, which affects the prognosis of hepatocellular carcinoma (HCC), is not clear. This article aimed to observe the correlation between H2AFX and tumor tissue infiltration biomarkers in HCC and its prognostic potential in HCC. Oncomine and TIMER database were used to assess the expression level of H2AFX mRNA, and GEPIA and Kaplan-Meier databases were used to evaluate its prognostic potential. The TIMER database analyzed the relationship between h2afx expression level and tumor immune cell infiltration markers in liver cancer tissues. The results showed that H2AFX was overexpressed in tumor tissues than normal tissues in HCC via analysis, and its expression level was correlated with the survival rate of HCC. Moreover, the expression level of H2AFX was related to various immune biomarkers. These results show that overexpression of H2AFX would reflect the poor prognosis of HCC, and these would also reflect that the gene H2AFX can affect the infiltration of HCC immune cells and then play a role in regulating tumor immunity. Our study showed that the gene H2AFX might be a potential poor prognostic biomarker in HCC and might be involved in the infiltration of HCC immune cells.

The hypoxia-inducible factor 1 inhibitor LW6 mediates the HIF-1α/PD-L1 axis and suppresses tumor growth of hepatocellular carcinoma in vitro and in vivo

The low survival rate of hepatocellular carcinoma (HCC) remains a major challenge for clinicians and patients, and its progression may be related to hypoxia-inducible factor (HIF) and PD-L1. LW6 is a drug that inhibits hypoxia by reducing HIF-1α accumulation and gene transcriptional activity. However, its effect and regulatory mechanism in HCC remain to be revealed, especially under hypoxic conditions. The HIF-1α and PD-L1 expression in HCC specimens and paracarcinoma tissues was evaluated by a tissue microarray (TMA). The effects of LW6 were evaluated by cell viability, colony formation, and Transwell assays and xenografted nude mice. Cell cycle and apoptosis of HCC cells were detected by flow cytometry. The effects of LW6 on HIF-1α signaling and its targets PD-L1 and VEGF were evaluated through qRT-PCR, Western blots, Cell transfection, Transwell migration and invasion assays, immunohistochemistry, immunofluorescence and luciferase assays. In this study, we found that LW6 had antiproliferative effects on HCC and promoted HCC cell apoptosis, inhibited their migration and invasion, and affected their cell cycle. LW6 dramatically decreased HIF-1α expression through the VHL-dependent proteasome system pathway, inhibited HIF-1α transcriptional activation, and reduced PD-L1 expression by inhibiting EGFR pathway activation. These results suggest that LW6 can promote apoptosis of HCC cells by inhibiting HIF-1α, inhibit tumor angiogenesis, and downregulate the expression of PD-L1, which is an effective choice for the treatment of HCC. Moreover, inhibiting the hypoxic microenvironment combined with immunotherapy is expected to be a potentially effective strategy.

Diluted Lycopodium Induced Cell Death and Clinical Improvement in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a common cancer with high incidence rate, and 5-year survival rate in HCC is less than 20%. Thus, in search of newer anticancer agents effective in HCC, we have explored possible usefulness of an alternative medicine Lycopodium against the human liver cancer cell line, HepG2 along with its clinical efficacy. The HepG2 cell line was challenged with Lycopodium 6C (diluted Lycopodium &lt;1pg /mL available as alternative medicine) along with vehicle alcohol control in 24 hours. The cytopathic effect and viability test with methylene blue stain were observed. The cells were harvested for total RNA extraction, and gene expression levels of targeted cytokines -Interferon gamma (IFN γ); Interleukins - IL-6, IL-8, IL-10, IL-1β, Transforming Growth Factor- TGF-β1, TGF-β3 and Tumor Necrosis Factor alpha (TNF-α) by RT-PCR were studied. DNA fragmentation assay and cell viability assay by MTT method were also tested. After ethical permission we applied this medicine as adjunct therapy to observe any beneficial role of the medicine. Statistically significant changes of IL-10, IL-1β and TGF-β3 were observed after challenge with Lycopodium 6C. The IL-10 gene expression in malignant cells was significantly reduced with Lycopodium 6C; however, the expression is more with vehicle alcohol compared to normal control set. Thus, the medicine could decrease the excessive IL-10 gene expression to a moderate level. IL-1β and TGF-β3 gene up-regulation by the vehicle alcohol were also mitigated by the medicine Lycopodium 6C. Mild DNA fragmentation was also seen in cancer cells after challenge with the medicine. Two cases suffering from hepatocellular carcinoma showed much clinical improvement after therapy with this medicine. Lycopodium 6C may act as a supporting alternative medication for treating HCC.

EPH4 Incidence and Survival of Patients with Hepatocellular Carcinoma in the United States from 2008 to 2018

Hepatocellular Carcinoma (HCC) is the most prevalent primary liver cancer in adults, and it is one of the fastest-rising causes of cancer-related deaths in the US. This study examined the incidence and survival rates for HCC in recent years.

Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug

New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug.

Identification of the Pyroptosis-Related Prognosis Gene Signature and Immune Infiltration in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most heterogeneous malignancies worldwide with a dismal prognosis. Lack of efficient biomarkers, early detection, and prognosis is still a challenge for HCC. Pyroptosis is a new discovery inflammatory form of programmed cell death. There is growing evidence revealed that pyroptosis plays a role in physiological and pathological conditions of human cancers. However, the prognostic evaluation of these pyroptosis-related genes (PRGs) in HCC remains blank. Consensus clustering of PRGs was used to classify 374 patients with HCC from the TCGA-LIHC cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 2-gene prognostic gene model (PLCG1 and GSDMC) was built and indicated the survival rate in HCC with medium-to-high accuracy. Then, the median risk score from the TCGA cohort was utilized; the prognostic gene model was also accurate in Gene Expression Omnibus (GEO) cohort. The functional enrichment analysis indicated that the oncogenic properties are associated with prominent hallmarks of cancer. The ssGSEA analyses and TIMER database indicated that immune infiltration tumor microenvironment in the HCC. In conclusion, our findings provide a foundation for further research targeting PRGs and their immune microenvironment.

Identification and Validation of Hub Genes with Poor Prognosis in Hepatocellular Carcinoma by Integrated Bioinformatical Analysis.

BackgroundHepatocellular carcinoma (HCC) is the reason for the world’s second largest cancer-related death. It is clinically valuable to study the molecular mechanisms of HCC occurrence and development for formulating more effective diagnosis and treatment strategies.MethodsThe five microarray data sets GSE45267, GSE101685, GSE84402, GSE62232 and GSE45267 were downloaded from Gene Expression Omnibus (GEO) database, including 165 HCC tissues and 73 normal tissues. Differential expressed genes (DEGs) between HCC tissues and normal tissues were determined by GEO2R. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and the protein–protein interaction network (PPI) network analysis were employed to identify DEGs and to evaluate the clinical significance in prognosis of HCC.ResultsA total of 152 genes differentially expressed in HCC tissues and normal tissues were identified. GO and KEGG functional enrichment analysis revealed that 39 up-regulated genes were mainly enriched in mitosis, cell cycle and oocyte meiosis, while those down-regulated genes (113) were concentrated in exogenous drug catabolism and the metabolism of cytochrome P450 on exogenous drugs. Totally, 19 hub genes were chosen by PPI network and module analysis and verified by The Cancer Genome Atlas (TCGA) database. Finally, 8 hub genes were selected, including CDK1, CYP2C8, CCNB1, AURKA, CYP2C9, BUB1B, MAD2L1 and TTK, which were associated with the overall survival rate of HCC patients.ConclusionThis study presented eight target genes connected to the prognosis of HCC patients. Those mainly exists in cell cycle and drug catabolism, which may be latent targets for clinical treatment.

ZCCHC17 Served as a Predictive Biomarker for Prognosis and Immunotherapy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the common malignant tumors. The prognosis and five-year survival rate of HCC are not promising due to tumor recurrence and metastasis. Exploring markers that contribute to the early diagnosis of HCC, markers for prognostic evaluation of HCC patients, and effective targets for treating HCC patients are in the spotlight of HCC therapy. Zinc Finger CCHC-Type Containing 17 (ZCCHC17) encodes the RNA binding protein ZCCHC17, but its role in HCC is still unclear. Here, 90 paraffin-embedded specimens combined with bioinformatics were used to comprehensively clarify the value of ZCCHC17 in the diagnosis and prognosis of HCC and its potential functions. Paraffin-embedded specimens were used to assess ZCCHC17 protein expression and its correlation with prognosis in 90 HCC patients. the public data sets of HCC patients from TCGA, ICG, and GEO databases were also used for further analysis. It was found that protein and mRNA levels of ZCCHC17 in HCC tissues were significantly higher than those in normal tissues. The abnormally high expression may be related to the abnormal DNA methylation of ZCCHC17 in tumor tissues. The high expression of ZCCHC17 is related to AFP, histologic grade, tumor status, vascular invasion, and pathological stage. Multi-data set analysis showed that patients with high ZCCHC17 expression had a worse prognosis, and multivariate cox regression analysis showed an independent prognostic significance of ZCCHC17. The results of functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA), indicate that ZCCHC17 is mainly involved in immune regulation. Subsequently, further single-sample gene set enrichment analysis (ssGSEA) showed that the expression of ZCCHC17 was related to the infiltration of immune cells. Importantly, we also analyzed the relationship between ZCCHC17 and immune checkpoint genes, tumor mutation burden (TMB), microsatellite instability (MSI) and TP53 status in HCC patients and evaluated the role of ZCCHC17 in cancer immunotherapy. In summary, ZCCHC17 is a novel marker for the diagnosis and prognostic evaluation of HCC. Concurrently, it regulates immune cells in the tumor microenvironment (TME) of HCC patients, which has a specific reference value for the immunotherapy of HCC.

Report of the 22nd nationwide follow-up Survey of Primary Liver Cancer in Japan (2012-2013).

In the 22nd Nationwide Follow-up Survey of Primary Liver Cancer in Japan, data from 21 155 newly registered patients and 43 041 previously registered follow-up patients were compiled from 538 institutions over a 2-year period from January 1, 2012 to December 31, 2013. Basic statistics compiled for patients newly registered in the 22nd survey were cause of death, past medical history, clinical diagnosis, imaging diagnosis, treatment-related factors, pathologic diagnosis, recurrence status and autopsy findings. Compared with the previous 21st survey, the population of patients with hepatocellular carcinoma (HCC) was older at the time of clinical diagnosis, had more female patients, more patients with non-B non-C HCC, smaller tumor diameter and was more frequently treated with hepatectomy. Cumulative survival rates were calculated for HCC, intrahepatic cholangiocarcinoma, and combined hepatocellular cholangiocarcinoma (combined HCC and intrahepatic cholangiocarcinoma) by treatment type and background characteristics for patients newly registered between 2002 and 2013 whose final outcome was survival or death. Median overall survival and cumulative survival rates for HCC were calculated by dividing patients by combinations of background factors (number of tumors, tumor diameter or Child-Pugh grade) and by treatment type (hepatectomy, radiofrequency ablation therapy, transcatheter arterial chemoembolization, hepatic arterial infusion chemotherapy and systemic therapy). The same values were also calculated according to registration date by dividing patients newly registered between 1978 and 2013 into five time period groups. The data obtained from this nationwide follow-up survey are expected to contribute to advancing clinical research and treatment of primary liver cancer worldwide.

A Novel Nine-lncRNA Risk Signature Correlates With Immunotherapy in Hepatocellular Carcinoma.

BackgroundHepatocellular carcinoma is one of the most common malignant tumors with a very high mortality rate. The emergence of immunotherapy has brought hope for the cure of hepatocellular carcinoma. Only a small number of patients respond to immune checkpoint inhibitors, and ferroptosis and tertiary lymphoid structure contribute to the increased response rate of immune checkpoint inhibitors; thus, we first need to identify those who are sensitive to immunotherapy and then develop different methods to improve sensitivity for different groups.MethodsThe sequencing data of hepatocellular carcinoma from The Cancer Genome Atlas and Gene Expression Omnibus was downloaded to identify the immune-related long non-coding RNAs (lncRNAs). LncRNAs related to survival data were screened out, and a risk signature was established using Cox proportional hazard regression model. R software was used to calculate the riskScore of each patient, and the patients were divided into high- and low-risk groups. The prognostic value of riskScore and its application in clinical chemotherapeutic drugs were confirmed. The relationship between riskScore and immune checkpoint genes, ferroptosis genes, and genes related to tertiary lymphoid structure formation was analyzed by Spearman method. TIMER, CIBERSORT, ssGSEA, and ImmuCellAI were used to evaluate the relative number of lymphocytes in tumor. The Wilcoxon signed-rank test confirmed differences in immunophenoscore between the high- and low-risk groups.ResultsData analysis revealed that our signature could well predict the 1-, 2-, 3-, and 5-year survival rates of hepatocellular carcinoma and to predict susceptible populations with Sorafenib. The risk signature were significantly correlated with immune checkpoint genes, ferroptosis genes, and tertiary lymphoid structure-forming genes, and predicted tumor-infiltrating lymphocyte status. There was a significant difference in IPS scores between the low-risk group and the high-risk group, while the low-risk group had higher scores.ConclusionThe riskScore obtained from an immune-related lncRNA signature could successfully predict the survival time and reflect the efficacy of immune checkpoint inhibitors. More importantly, it is possible to select different treatments for different hepatocellular carcinoma patients that increase the response rate of immune checkpoint inhibitors and will help improve the individualized treatment of hepatocellular carcinoma.

Evaluate Survival Rate of Hepatocellular Carcinoma in Yazd from 1390 to 1394

Objectives: Liver cancer is one of the five most common cancer and the second leading cause of cancer death in men worldwide and the seventh most common cancer and the sixth leading cause of death in women from cancers. Liver cancer was the tenth most common cancer in Yazd in 1388 to 19% in women and 26% of males that has been more prevalent than in other provincial capitals. Methods: This cross-sectional descriptive study is a census of patients with hepatocellular carcinoma who referred to Yazd hospital pathology centers. All samples that have complete data from 1390 to 1394 were enrolled in the study. Information including age, sex, method of treatment and numbers of patients collected and then analyzed using statistical software spss 16 is placed. The aim of this study was to determine the survival rate of liver cancer patients according to age, sex, treatment, race and disease risk factors. Results: Of the 48 patients, 47.9% were female and 52.1% male during the five years . the average of age in this study was 62.81years. of the patients studied was 62.81 years .93.8% of patients were Iranian race. In this study, median survival was 7.43 months. The diabetes melitus with a prevalence of 18.8% was most common among the risk factors. alcohol consumption and the prevalence of hepatitis C has the lowest prevalence that was 1.9%. 83% of patients in this study were treated but other don’t come satisfaction for any treatment. Conclusion: In this study, like other studies, the incidence of liver cancer in men was higher than women. Most were Iranian people and the relationship between race and survival was no significant relationship between age, type of treatment, such as surgery, radiotherapy or chemotherapy with survival rate was not significant. But after Cox regression between age, family history of liver cancer, diabetes and treatment with survival in patients with hepatocellular carcinoma, there was a significant relationship. Keywords: HCC, Yazd, Survival

Signature of prognostic epithelial-mesenchymal transition related long noncoding RNAs (ERLs) in hepatocellular carcinoma.

Reliable biomarkers are of great significance for the treatment and diagnosis of hepatocellular carcinoma (HCC). This study identified potential prognostic epithelial–mesenchymal transition related lncRNAs (ERLs) by the cancer genome atlas (TCGA) database and bioinformatics.The differential expression of long noncoding RNA (lncRNA) was obtained by analyzing the lncRNA data of 370 HCC samples in TCGA. Then, Pearson correlation analysis was carried out with EMT related genes (ERGs) from molecular signatures database. Combined with the univariate Cox expression analysis of the total survival rate of hepatocellular carcinoma (HCC) patients, the prognostic ERLs were obtained. Then use “step” function to select the optimal combination of constructing multivariate Cox expression model. The expression levels of ERLs in HCC samples were verified by real-time quantitative polymerase chain reaction.Finally, we identified 5 prognostic ERLs (AC023157.3, AC099850.3, AL031985.3, AL365203.2, CYTOR). The model showed that these prognostic markers were reliable independent predictors of risk factors (P value <.0001, hazard ratio [HR] = 2.400, 95% confidence interval [CI] = 1.667–3.454 for OS). In the time-dependent receiver operating characteristic analysis, this prognostic marker is a good predictor of HCC survival (area under the curve of 1 year, 2 years, 3 years, and 5 years are 0.754, 0.720, 0.704, and 0.662 respectively). We analyzed the correlation of clinical characteristics of these prognostic markers, and the results show that this prognostic marker is an independent factor that can predict the prognosis of HCC more accurately. In addition, by matching with the Molecular Signatures Database, we obtained 18 ERLs, and then constructed the HCC prognosis model and clinical feature correlation analysis using 5 prognostic ERLs. The results show that these prognostic markers have reliable independent predictive value. Bioinformatics analysis showed that these prognostic markers were involved in the regulation of EMT and related functions of tumor occurrence and migration.Five prognostic types of ERLs identified in this study can be used as potential biomarkers to predict the prognosis of HCC.

Tumor Microenvironment Alters Chemoresistance of Hepatocellular Carcinoma Through CYP3A4 Metabolic Activity.

Variations in tumor biology from patient to patient combined with the low overall survival rate of hepatocellular carcinoma (HCC) present significant clinical challenges. During the progression of chronic liver diseases from inflammation to the development of HCC, microenvironmental properties, including tissue stiffness and oxygen concentration, change over time. This can potentially impact drug metabolism and subsequent therapy response to commonly utilized therapeutics, such as doxorubicin, multi-kinase inhibitors (e.g., sorafenib), and other drugs, including immunotherapies. In this study, we utilized four common HCC cell lines embedded in 3D collagen type-I gels of varying stiffnesses to mimic normal and cirrhotic livers with environmental oxygen regulation to quantify the impact of these microenvironmental factors on HCC chemoresistance. In general, we found that HCC cells with higher baseline levels of cytochrome p450-3A4 (CYP3A4) enzyme expression, HepG2 and C3Asub28, exhibited a cirrhosis-dependent increase in doxorubicin chemoresistance. Under the same conditions, HCC cell lines with lower CYP3A4 expression, HuH-7 and Hep3B2, showed a decrease in doxorubicin chemoresistance in response to an increase in microenvironmental stiffness. This differential therapeutic response was correlated with the regulation of CYP3A4 expression levels under the influence of stiffness and oxygen variation. In all tested HCC cell lines, the addition of sorafenib lowered the required doxorubicin dose to induce significant levels of cell death, demonstrating its potential to help reduce systemic doxorubicin toxicity when used in combination. These results suggest that patient-specific tumor microenvironmental factors, including tissue stiffness, hypoxia, and CYP3A4 activity levels, may need to be considered for more effective use of chemotherapeutics in HCC patients.