Characteristics Of Hepatocellular Carcinoma Patients Research Articles

Systemic chemotherapy improves outcome of hepatocellular carcinoma patients treated with transarterial chemoembolization

BackgroundTransarterial chemoembolization (TACE) based neoadjuvant therapy was proven effective in hepatocellular carcinoma (HCC). Recently, tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) also showed promise in HCC treatment. However, the prognostic benefits associated with these treatments remain uncertain. This study aimed to explore the relationship between pathologic response and prognostic features in HCC patients who received neoadjuvant therapy. MethodsHCC patients who received TACE either with or without TKIs/ICIs as neoadjuvant therapy before liver resection were retrospectively collected from the First Affiliated Hospital, Zhejiang University School of Medicine in China. Pathologic response was determined by calculating the proportion of non-viable area within the tumor. Major pathologic response (MPR) was defined as the presence of non-viable tumor cells reaching a minimum of 90 %. Complete pathologic response (CPR) was characterized by the absence of viable cells observed in the tumor. ResultsA total of 481 patients meeting the inclusion criteria were enrolled, with 76 patients (15.8 %) achieving CPR and 179 (37.2 %) reaching MPR. The median recurrence-free survival (mRFS) in the CPR + MPR group was significantly higher than the non-MPR group (31.3 vs. 25.1 months). The difference in 3-year overall survival (OS) rate was not significant (90.2 % vs. 87.6 %). Multivariate Cox regression analysis identified failure to achieve MPR (hazard ratio = 1.548, 95 % confidence interval: 1.122–2.134; P = 0.008), HBsAg positivity (HR = 1.818, 95 % CI: 1.062–3.115, P = 0.030), multiple lesions (HR = 2.278, 95 % CI: 1.621–3.195, P < 0.001), and baseline tumor size > 5 cm (HR = 1.712, 95 % CI: 1.031–2.849, P = 0.038) were independent risk factors for RFS. Subgroup analysis showed that 67 of 93 (72.0 %) patients who received the combination of TACE, TKIs, and ICIs achieved MPR + CPR. ConclusionsIn individuals who received TACE-based neoadjuvant therapy for HCC, failure to achieve MPR emerges as an independent risk factor for RFS. Notably, the combination of TACE, TKIs, and ICIs demonstrated the highest rate of MPR.

Clinical Nomogram Model for Pre-Operative Prediction of Microvascular Invasion of Hepatocellular Carcinoma before Hepatectomy.

Background and Objectives: Microvascular invasion (MVI) significantly impacts recurrence and survival rates after liver resection in hepatocellular carcinoma (HCC). Pre-operative prediction of MVI is crucial in determining the treatment strategy. This study aims to develop a nomogram model to predict the probability of MVI based on clinical features in HCC patients. Materials and Methods: A total of 489 patients with a pathological diagnosis of HCC were enrolled from our hospital. Those registered from 2012-2015 formed the derivation cohort, and those from 2016-2019 formed the validation cohort for pre-operative prediction of MVI. A nomogram model for prediction was created using a regression model, with risk factors derived from clinical and tumor-related features before surgery. Results: Using the nomogram model to predict the odds ratio of MVI before hepatectomy, the AFP, platelet count, GOT/GPT ratio, albumin-alkaline phosphatase ratio, ALBI score, and GNRI were identified as significant variables for predicting MVI. The Youden index scores for each risk variable were 0.287, 0.276, 0.196, 0.185, 0.115, and 0.112, respectively, for the AFP, platelet count, GOT/GPT ratio, AAR, ALBI, and GNRI. The maximum value of the total nomogram scores was 220. An increase in the number of nomogram points indicated a higher probability of MVI occurrence. The accuracy rates ranged from 55.9% to 64.4%, and precision rates ranged from 54.3% to 68.2%. Overall survival rates were 97.6%, 83.4%, and 73.9% for MVI(-) and 80.0%, 71.8%, and 41.2% for MVI(+) (p < 0.001). The prognostic effects of MVI(+) on tumor-free survival and overall survival were poor in both the derivation and validation cohorts. Conclusions: Our nomogram model, which integrates clinical factors, showed reliable calibration for predicting MVI and provides a useful tool enabling surgeons to estimate the probability of MVI before resection. Consequently, surgical strategies and post-operative care programs can be adapted to improve the prognosis of HCC patients where possible.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

Non-Alcoholic Fatty Liver Disease-Associated Hepatocellular Carcinoma: Effect of Hepatic Steatosis on Major Hepatocellular Carcinoma Features at MRI

Background Non-alcoholic fatty liver disease has become the leading chronic liver disease in the developed world, with a prevalence of 6%-35%. Its pathological spectrum ranges from simple steatosis (non-alcoholic fatty liver) to different degrees of inflammation and liver cell damage [nonalcoholic steatohepatitis (NAFLD)]. NAFLD has gained attention in recent years because of its association with hepatocellular carcinoma (HCC). Objective To see how hepatic fat fraction affects LIRADS major hepatocellular carcinoma features on magnetic resonance imaging. Patients and Methods Our study included 60 patients who had had a liver MR scan and exhibited MRI features in keeping with HCC. We categorize the patients into two groups: hepatic steatosis and non- hepatic steatosis groups based on MRI hepatic fat signal fraction. LI-RADS major and ancillary features were evaluated in all HCCs. Between October 2021 and April 2022, a retrospective search was conducted to find all patients with HCC who underwent an MRI of the liver at the radiology department of Ain Shams University's Faculty of medicine. Results In the current study, a higher proportion of HCCs show non- enhancing capsule in patients with hepatic steatosis; 5 HCC (5/30; 16.7%), while in the non-hepatic steatosis group no HCCs 0 (0%) showed non-enhancing capsule. The effect of ancillary features on diagnostic accuracy is still being researched. As regards the impact of the degree of fatty liver on the major and ancillary HCC features, the “enhancing capsule”, “mild-moderate T2 hyperintensity” and “restricted DWI” features are less commonly seen in cases of moderate to severe hepatic steatosis than in those of mild hepatic steatosis. Our study also showed that HCCs tends to be of a smaller size as the hepatic steatosis degree increased. Conclusion The findings of our retreopective study are coincide with a recent retrospective studies demonstrated that “enhancing capsule” feature of HCC was less frequently observed in patients with hepatic steatosis compared to non-hepatic steatosis patients. We compared the MRI features of HCC in patients with hepatic steatosis to those in patients without hepatic steatosis. Our findings imply that existing imaging criteria for the noninvasive characterization of HCC in individuals with hepatic steatosis should be utilised with care.

Characterization of stem cell subtypes and prognostic signature in hepatocellular carcinoma.

Cancer stem cells (CSCs) were linked to cancer aggressiveness and poor prognosis in patients with hepatocellular carcinoma (HCC). We integrated two external HCC cohorts to develop the stem cell subtypes according to unsupervised clustering with 26 stem cell gene sets. Between the subtypes, differences in prognosis, clinical characteristics, recognized HCC subtypes, metabolic profile, immune-related features, somatic mutation, and drug sensitivity were examined. The prognostic signature was created, and validated by numerous cohorts, and used to assess the efficacy of immunotherapy and transcatheter arterial chemoembolization (TACE) treatment. The nomogram was developed based on the signature and clinical features. We further examined the function of KIF20A in HCC and proved that KIF20A had the potential to regulate the stemness of HCC cells through western blot. Low stem cell patterns, a good prognosis, positive clinical features, specific molecular subtypes, low metastatic characteristics, and an abundance of metabolic and immunological aspects were associated with Cluster 1, whereas Cluster 2 was the reverse. Chemotherapy and immunotherapy were more effective in Cluster 1. Cluster 1 and CTNNB1 and ALB mutation were more closely. Additionally, the prognosis, immunotherapeutic, and TACE therapy responses were all worse in the high-risk group. The nomogram could predict the survival probability of HCC patients. KIF20A was discovered to be overexpressed in HCC and was revealed to be connected to the stemness of the HepG2 cell line. Two stem cell subgroups with different prognoses, metabolic, and immunological characteristics in HCC patients were identified. We also created a 7-gene prognostic signature and a nomogram to estimate the survival probability. The function of KIF20A in HCC stemness was initially examined.

Fibulin-2 Facilitates Malignant Progression of Hepatocellular Carcinoma.

Identification of biomarkers to assist in the clinical management of hepatocellular carcinoma represents an urgent requirement. Fibulin-2 is known to contribute to the development and progression of various cancer types. This research investigated the role of fibulin-2 in hepatocellular carcinoma and explored the possible mechanisms. The expression of fibulin-2 in hepatocellular carcinoma was measured by bioinformatic analysis and confirmed by western blot and immunohistochemical staining in cell lines or patients' samples. The clinicopathologic features of hepatocellular carcinoma patients was analyzed. Cell viability assays were used to explore the role of fibulin-2 on proliferation in hepatocellular carcinoma. Western blot was conducted to uncover changes of protein expression of Ras-MEK-ERK1/2 pathway when Fibulin-2 was overexpressed or silenced. Flow cytometry analyses were used to determine the roles of fibulin-2 in the function of apoptosis and cell cycle. Subcutaneous xenograft mouse models showed the tumor growth pattern after fibulin-2 silence in vivo. We reported the upregulation of fibulin-2 in most hepatocellular carcinoma tissues and cells lines. Fibulin-2 promoted the proliferation of hepatocellular carcinoma cells in vitro by regulating Ras-MEK-ERK1/2 signaling pathway, whereas knockdown of fibulin-2 incurred the opposite effect on proliferation. Consistently, knockdown of fibulin-2 resulted in increased apoptosis and induced growth arrest during the G0/G1 phase transition. In vivo xenograft assessment confirmed that knockdown of fibulin-2 inhibited hepatocellular carcinoma tumor growth. Fibulin-2 exhibited tumor promotor activities in malignant progression of hepatocellular carcinoma. The results of the study highlighted the potential of fibulin-2 to be utilized as a promising biomarker and therapeutic target for hepatocellular carcinoma.

THU-121 - Genomic characteristics of hepatocellular carcinoma patients with response to sorafenib

THU-121 - Genomic characteristics of hepatocellular carcinoma patients with response to sorafenib

Equilibrative nucleoside transporter 3 promotes the progression of hepatocellular carcinoma by regulating the AKT/mTOR signaling pathway

Equilibrative nucleoside transporter 3 (ENT3) belongs to the solute carrier family 29. Nucleoside transporters encoded by ENT3 play an important role in the uptake of nucleosides, nucleobases, and their nucleoside analogs, as well as participate in and regulate several physiological activities. However, no study has so far reported the role of ENT3 in hepatocellular carcinoma (HCC). We employed bioinformatics to analyze the expression, prognosis, and mechanism of ENT3 in HCC, as well as verified the same through biological experiments including cell proliferation, cell migration and invasion, and cell cycle and apoptosis, along with the detection of the AKT/mTOR protein expression in the pathway by Western blotting. ENT3 was widely and highly expressed in pan-cancer and upregulated in HCC. The upregulated ENT3 was related to the poor prognosis and clinical features in HCC patients. ENT3 knockdown inhibited cell proliferation, migration, and invasion and promoted cell apoptosis. ENT3 knockdown reduced the p-AKT and p-mTOR protein phosphorylation level, inhibited p-p70S6K1 and increased the p-4EBP1—the downstream effector of the AKT/mTOR pathway—protein phosphorylation level. Our study findings demonstrated that the expression of ENT3 was upregulated in HCC, which represents a poor prognosis. Thus, ENT3 promotes the progression of HCC through the AKT/mTOR signaling pathway.

Pseudogene PLGLA exerts anti-tumor effects on hepatocellular carcinoma through modulating miR-324-3p/GLYATL1 axis.

Pseudogenes are dysfunctional copies of protein-coding genes that showed critical regulatory roles during carcinogenesis. Plasminogen like A (PLGLA) is a transcribed unprocessed pseudogene and biasedly expressed in liver. But its function has not been studied in hepatocellular carcinoma (HCC). We aimed to explore the role of PLGLA in HCC. The expression of PLGLA and its association with pathological features in HCC patients was analyzed using The Cancer Genome Atlas (TCGA) datasets. Quantitative reverse transcription PCR (qRT-PCR) was used to validate PLGLA level in HCC tissue samples and cell lines. Gain-of-function experiments in vitro and in vivo were employed to assess the impact of PLGLA on HCC cell proliferation, migration and invasion. Luciferase reporter assay and RNA pull-down assay were conducted to confirm the interaction among PLGLA, miR-324-3p and GLYATL1. PLGLA expression was significantly downregulated in HCC tissues and cell lines. Furthermore, low PLGLA expression was positively associated with tumor progression and poor prognosis. PLGLA restoration markedly suppressed cell proliferation, migration and invasion. Mechanistically, PLGLA could competitively bind to miR-324-3p and acted as a competitive endogenous RNA (ceRNA) to enhance GLYATL1 expression. Our results established a novel tumor suppressive role of PLGLA in HCC pathogenesis and highlighted its potential as a therapeutic target for HCC treatment.

Clinical utility of immunotherapy hyperprogressive genes in hepatocellular carcinoma patients.

e16126 Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy associated with poor prognosis. With the rapid development of systematic therapy for liver cancer, immunotherapy has been widely used in therapy of liver cancer. Hyperprogression of tumor is a phenomenon of accelerated tumor growth, which occurs in patients with liver cancer and other solid tumors receiving systematic treatment, and is mainly related to immunotherapy hyperprogression genes. However, it is still unclear about the genes of immune hyperprogression in HCC patients. Therefore, we studied the molecular characteristics of HCC patients, including the genes related to immunotherapy hyperprogression. Methods: From June 2019 to August 2021, 102 patients with HCC were inculded in this study. Matched tumor/normal DNA from HCC patients (N = 102) were analyzed by whole exome sequencing (WES) or Acornmed panel with 808 cancer-related genes. Results: Overall, 86.3% (88/102) patients exhibited genetic alterations. TP53 (50%), TERT (23%), CTNNB1 (18%) and KMT2C (14%) were the most commonly mutated genes in HCC. In addition, 8.9% patinets harbored at least one immunotherapy hyperprogressive gene mutations, including CCND1 (7%), FGF19 (6%), FGF3 (5%), FGF4 (5%) and MDM4 (2%). In addition, CCND1 and FGF19 were frequently mutated genes in patients with liver cancer, ranking ninth and tenth, respectively. Compared with the TCGA data, there was no significant difference in immunotherapy hyperprogressive genes (25% vs 32.3%, p = 0.18). Interesting, CCND1, FGF19, FGF3 and FGF4 mutations occurred simultaneously in most patients and were mutually exclusive with MDM4 (p = 0.057). Conclusions: This study contributes to understand the molecular characteristics of patients with HCC, which will be useful to guide immunotherapy and promote the clinical management in this population. Furthermore, the study suggested that both Chinese and Western populations should pay attention to immunotherapy hyperprogression genes in immunotherapy selection.

THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation.

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.

MiR-500a-3p is a Potential Prognostic Biomarker in Hepatocellular Carcinoma.

PurposemiR-500a-3p has been extensively reported to be implicated in the development and progression in several human cancer types. This study aimed to investigate the diagnostic and prognostic significance of miR-500a-3p as a biomarker in hepatocellular carcinoma (HCC).MethodsmiR-500a-3p expression was evaluated by in situ hybridization (ISH) and real-time PCR in 10 adjacent normal tissues (ANT), 21 liver fibrosis tissues, and 110 HCC tissues. Statistical analysis was used to investigate the correlation of miR-500a-3p expression with clinicopathological features in HCC patients. Kaplan–Meier survival analysis was performed to evaluate the prognostic significance of miR-500a-3p in overall survival and recurrence-free survival in HCC patients.ResultsIn this study, we found that expression levels of miR-500a-3p were enhanced in HCC tissues. High miR-500a-3p levels were positively correlated with multiple clinicopathological features, including advanced clinical stage, distant metastatic status, increased AFP levels and poor tumor differentiation degree. More importantly, high miR-500a-3p levels predicted poor overall survival and early recurrence in HCC patients. Finally, a strong and positive correlation of miR-500a-3p mRNA expression with ISH staining scores was observed in clinical HCC tissues.ConclusionOur findings suggest that miR-500a-3p might be used as a novel biomarker to facilitate early diagnosis and predict prognosis in HCC patients.

HEPATOCELLULAR CARCINOMA: CLINICAL AND EPIDEMIOLOGICAL FEATURES IN VERACRUZ

Hepatocellular carcinoma (HCC) is the most frequent liver tumor and it occupies sixth place of the malignant neoplasms worldwide. In the last decades, In Mexico has been reported an increase of 95% in incidence and 14% in mortality, becoming the second most lethal neoplasm after pancreatic cancer. Few studies describe the HCC epidemiological behavior in our population. To describe the clinical and epidemiological features of HCC in patients from Veracruz city. A descriptive and retrospective study was done from a patient database with diagnosed HCC by imaging and, if required, with a biopsy confirmation between 2005 and 2021 in Veracruz. Central tendency and dispersion measures were done for the analysis. 130 patients with HCC were studied, the mean diagnosis age was 66.9±11 (29-62 rate), with a female genre lead 1.2:1. Eighty-six patients (66.2%) had cirrhosis at the diagnosis, 32 (24.6%) were secondary to chronic alcohol consumption, 8 (6.2%) with hepatitis C infection, 20 (15.4%) MAFLD/ Cryptogenic and 3 (2.3%) with hepatitis B infection. The comorbidities reported were overweight in 58 patients (43.9%), obesity 19 (14.4%), high blood pressure 54 (40.2%) and diabetes mellitus 51 (38.6%). The most frequent biochemical disturbance was hyperbilirubinemia (1.27±1.26). The rest f biochemical features are described in table 1. Sixty-six patients (50%) were found with Child-Pugh A with a MELD score of 9.86±3.0. In this stage, we found 74 patients (56.9%) with Barcelona B, 80% had a lone tumor, the mean tumoral size was 7.13±3.7 cm. 69.2% of patients had a tumoral size greater than 5 cm at the diagnosis. Our results show that the HCC behavior is similar to the reported in previous Mexican studies, predominating in patients with advanced liver injury and tumor outside criteria of local treatment at the diagnosis. The high frequency of comorbidities associated with metabolic syndrome is remarkable as one of the main risk factors with chronic C virus infection. HCC in Mexico has been increasing. It shows similar epidemiological features with the reported in other populations due to its relationship with metabolic risk. Early screening in high-risk patients results in greater resectability and survival. The authors declare that there is no conflict of interest.

Environmental exposure and clinical correlates of hepatocellular carcinoma in New York City: a case only study.

In the U.S., Hepatocellular carcinoma (HCC) incidence rates have increased. We aimed to determine whether environmental exposure plays a role in the high incidence of HCC observed in New York City. We conducted a hospital-based case only study to examine the prevalence of aflatoxin B1 (AFB1)- and polycyclic aromatic hydrocarbon (PAH)-albumin adducts and the distribution of adducts by different characteristics of HCC patients. Blood samples were collected from 155 HCC patients for biomarker analyses.We observed that about 46% and 49% of cases had detectable AFB1- and PAH-albumin adducts, respectively. There were significant differences between AFB1-albumin adducts and selected factors such as HCV infection status (p = 0.04), diabetes (p = 0.03) and Barcelona Clinic Liver Cancer stage (p = 0.02). Cases with detectable PAH-albumin adducts had a smoking history compared with those with nondetectable levels (p = 0.04). The level of AFB1-albumin adducts was positively correlated with plasma bilirubin (rs = 0.32, p < 0.0001) and adiponectin concentrations (rs = 0.28, p = 0.0005). The level of aflatoxin B1-albumin adducts was negatively associated with blood albumin concentration (rs = -0.28, p = 0.0009) and plasma DNA LINE-1 methylation (rs = -0.16, p = 0.04). Our study provides additional evidence that environmental exposures including to aflatoxin might drive the high incidence of HCC observed in the New York City.

Xanthine dehydrogenase as a prognostic biomarker related to tumor immunology in hepatocellular carcinoma

BackgroundXanthine dehydrogenase (XDH) is a critical enzyme involved in the oxidative metabolism of purines, pterin and aldehydes and a central component of the innate immune system. However, the prognostic value of XDH in predicting tumor-infiltrating lymphocyte abundance, the immune response, and survival in different cancers, including hepatocellular carcinoma (HCC), is still unclear.MethodsXDH expression was analyzed in multiple databases, including Oncomine, the Tumor Immune Estimation Resource (TIMER), the Kaplan–Meier plotter database, the Gene Expression Profiling Interactive Analysis (GEPIA) database, and The Cancer Genome Atlas (TCGA). XDH-associated transcriptional profiles were detected with an mRNA array, and the levels of infiltrating immune cells were validated by immunohistochemistry (IHC) of HCC tissues. A predictive signature containing multiple XDH-associated immune genes was established using the Cox regression model.ResultsDecreased XDH mRNA expression was detected in human cancers originating from the liver, bladder, breast, colon, bile duct, kidney, and hematolymphoid system. The prognostic potential of XDH mRNA expression was also significant in certain other cancers, including HCC, breast cancer, kidney or bladder carcinoma, gastric cancer, mesothelioma, lung cancer, and ovarian cancer. In HCC, a low XDH mRNA level predicted poorer overall survival, disease-specific survival, disease-free survival, and progression-free survival. The prognostic value of XDH was independent of the clinical features of HCC patients. Indeed, XDH expression in HCC activated several immune-related pathways, including the T cell receptor, PI3K-AKT, and MAPK signaling pathways, which induced a cytotoxic immune response. Importantly, the microenvironment of XDHhigh HCC tumors contained abundant infiltrating CD8 + T cells but not exhausted T cells. A risk prediction signature based on multiple XDH-associated immune genes was revealed as an independent predictor in the TCGA liver cancer cohort.ConclusionThese findings suggest that XDH is a valuable prognostic biomarker in HCC and other cancers and indicate that it may function in tumor immunology. Loss of XDH expression may be an immune evasion mechanism for HCC.

NET1 promotes HCC growth and metastasis in vitro and in vivo via activating the Akt signaling pathway.

Neuroepithelial cell transforming gene 1 (NET1), a member of the guanine nucleotide exchange factor family, is involved in various cancers, including gastric cancer, breast cancer and glioma. However, the role of NET1 in hepatocellular carcinoma (HCC) remains largely uncovered. In this study, we found that NET1 expression was upregulated in HCC, and that upregulated NET1 expression was closely associated with poor prognosis and some clinical characteristics in HCC patients. Whilst forced expression of NET1 in HCC cells was observed to significantly promote cell growth and metastasis in vitro and in vivo; downregulation of NET1 was shown to exhibit an opposite inhibitory effect. RNA-seq analysis and gene set enrichment analysis demonstrated that knockdown of NET1 significantly suppressed the level of Akt phosphorylation level and the expression of Akt downstream genes in HCC cells. Moreover, MK2206, a potent Akt inhibitor was shown to block the NET1-induced effects in HCC. Taken together, this study demonstrated that, through the Akt signaling pathway, NET1 plays an oncogenic role in HCC progression and metastasis. Hence, NET1 may potentially be used as a potential therapeutic target and prognostic marker of HCC.

No evidence of a more aggressive pattern of hepatocellular carcinoma after direct acting antivirals –results from a single center observational study

After great concerns were raised regarding a high incidence of hepatocellular carcinoma (HCC) after direct acting antivirals (DAAs) therapy in cirrhotic HCV patients, an avalanche of studies that debated this issue emerged, whose results highlighted also a more aggressive HCC pattern after DAAs. We aimed to assess the pattern and imaging features of HCC in patients with HCV-related liver cirrhosis after DAAs. Material and methods: This is a single-center case-controlled retrospective study in which we included consecutive patients with HCC and HCV-related liver cirrhosis admitted in our clinic between January 1st, 2016 and May 1st, 2018. Results: Sixty-nine patients with HCV-related cirrhosis and HCC were divided into 2 groups depending on the DAAs-treated or untreated status: group I included 15 patients that were previously treated with DAAs and group II included 54 naive patients. Regarding the distribution of HCC, there were no significant differences between the two groups (73.3% of group I patients and 55.5% of group II had unicentric lesion, p=0.215). The tumor size was significantly higher in group II compared to group I, with 66.6% of patients in group I and only 29.6% of patients in group II that have a tumor size less than 3 cm (p=0.009). Supportive treatment without ablation was more frequent in group II (33.3%) than in group I (6.6%) (p=0.047). Conclusions: Our study found no evidence of a more aggressive behavior of HCC after DAAs treatment compared to naive patients. Furthermore, the pattern of HCC after DAAs did not affect the access to curative treatment.

Prognostic value of γ-glutamyl transpeptidase to albumin ratio combined with aspartate aminotransferase to lymphocyte ratio in patients with hepatocellular carcinoma after hepatectomy.

Hepatocellular carcinoma (HCC) is a malignant tumor associated with a high recurrence rate after hepatectomy. Recently, preoperative inflammatory and liver function reserve indices were found to predict increased risk of recurrence and decreased survival in HCC patients. This study aims to evaluate the ability of the γ-glutamyl transpeptidase-to-albumin ratio (GAR) and aspartate aminotransferase-to-lymphocyte ratio (ALRI), individually and in combination, to predict the prognosis of HCC patients after hepatectomy.We retrospectively reviewed 206 HCC patients who underwent radical resection at the General Hospital of Ningxia Medical University from January 2011 to November 2016. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off value for GAR and ALRI. The Pearson Chi-Squared test was used to analyze the correlations between GAR, ALRI and clinicopathological characteristics. Univariate and multivariate analyses were used to determine the predictive value of these factors for disease-free survival (DFS) and overall survival (OS). Survival rates were drawn according to the Kaplan-Meier method and differences between subgroups were compared by the log-rank statistics.GAR and ALRI were significantly correlated with gender, history of smoking, prothrombin time, tumor diameter, T stage and early intrahepatic recurrence by the Pearson Chi-Squared test (all P < .05). Univariate analysis indicated that T stage, GAR and ALRI were significantly correlated with DFS and OS in HCC patients after hepatectomy. Multivariate analysis illustrated that GAR and ALRI were independently related to DFS and OS in HCC patients. Preoperative GAR > 0.946 or ALRI > 18.734 predicted poor prognosis in HCC patients after hepatectomy. Additionally, the predictive scope of GAR combined with ALRI was more sensitive than that of either individual measurement alone.Our data indicate that there is a close association between the clinicopathological characteristics in HCC patients and increased GAR or ALRI. Higher levels of GAR and ALRI could sensitively and specifically predict a poor prognosis in HCC patients after hepatectomy. Furthermore, combined usage of GAR and ALRI could improve the accuracy of this prediction.

Clinical Role of Newly Developed ALBI and mALBI Grades for Treatment of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a leading cause of death worldwide. The selection of therapeutic modalities and the prognosis of affected patients are well known to be dependent not only on the tumor burden but also on the hepatic reserve function. Antiviral treatments for chronic hepatitis related to a viral infection and an increase in cases of nonviral HCC associated with the aging of society have resulted in dramatic changes regarding the characteristics of HCC patients. With recent developments in therapeutic modalities for HCC, a more detailed assessment of hepatic function has become an important need. Studies in which the relationship of albumin-bilirubin (ALBI) grade with the prognosis of HCC patients was investigated were reviewed in order to evaluate the usefulness of newly developed ALBI and modified ALBI (mALBI) grades for HCC treatment, as those scoring methods are considered helpful for predicting the prognosis and selecting therapeutic modalities based on the expected prognosis.

LncRNA HAGLR exacerbates hepatocellular carcinoma through negatively regulating miR-6785-5p.

The purpose of this study was to explore the role of long non-coding RNA (lncRNA) HAGLR in exacerbating the development of hepatocellular carcinoma (HCC) by targeting microRNA-6785-5p (miR-6785-5p). HAGLR levels in 46 HCC tissues and paracancerous tissues were detected. The relationship between HAGLR level and clinical features of HCC patients was analyzed. After knockdown of HAGLR, proliferative, and metastatic potential changes in Bel-7402 and Hub7 cells were assessed. Thereafter, the interaction between HAGLR and miR-6785-5p, as well as the involvement of miR-6785-5p in HAGLR-regulated HCC phenotypes were finally determined. It was found that HAGLR level was higher in HCC tissues than paracancerous ones and correlated with rates of lymphatic metastasis and distant metastasis but not with age, gender, and tumor staging in HCC patients. Survival analysis uncovered that HAGLR level was negatively linked to overall survival in HCC. After knockdown of HAGLR, proliferative, and metastatic potentials in Bel-7402 and Hub7 cells were attenuated. MiR-6785-5p was proven as the target gene binding to HAGLR. It was lowly expressed in HCC species, and negatively correlated with HAGLR level. Moreover, rescue experiments demonstrated that miR-6785-5p was responsible for HAGLR-regulated HCC phenotypes. LncRNA HAGLR stimulates proliferative and metastatic potentials in HCC via negatively regulating miR-6785-5p level, thus exacerbating the development of HCC.