Clinical Features Of Hepatocellular Carcinoma Research Articles

Serum Aldo-Keto Reductase Family 1 Member B10 (AKR1B10) as a Potential Biomarker for Diagnosis of Hepatocellular Carcinoma.

To evaluate the diagnostic performance of aldo-keto reductase family 1 member B10 (AKR1B10) in a Beijing cohort with hepatocellular carcinoma (HCC). This study included 521 subjects who visited Peking Union Medical College Hospital from June 2017 to May 2023, including 109 cases of HCC, 165 cases of healthy controls, 106 cases of benign liver diseases, and 141 cases of other cancers. Serum AKR1B10 levels were measured and compared across various groups. Diagnostic performances of serum AKR1B10 and other tumor markers were assessed using receiver operator characteristic (ROC) curves. In addition, a subset of HCC patients who underwent surgical resection were recruited for clinical follow-up study. We found that serum AKR1B10 expression was higher in patients with HCC relative to other control groups. The association between serum AKR1B10 and clinical features of HCC was not observed. Serum AKR1B10 showed a high diagnostic performance for HCC, and when combined with AFP, the diagnostic effectiveness was significantly improved. Specifically, serum AKR1B10 showed superior diagnostic effectiveness for AFP-negative HCC. The clinical follow-up study indicated a gradual decrease in serum AKR1B10 after surgery. Our study demonstrated that serum AKR1B10 is a promising biomarker for HCC, and when used in combination with AFP can significantly improve the detection rate of HCC.

Sorcin regulate pyroptosis by interacting with NLRP3 inflammasomes to facilitate the progression of hepatocellular carcinoma

A high recurrence rate and easy metastasis are two prominent clinical features of hepatocellular carcinoma (HCC), which is also the most common cause of cancer-related death. However, the molecular pathogenesis of HCC remains unclear. Soluble resistance-related calcium-binding protein (Sorcin) is highly expressed in a variety of tumor cell lines and multidrug-resistant cell lines and participates in the malignant progression of tumors by regulating apoptosis. Pyroptosis is also a form of programmed cell death that plays a crucial role in exerting tumor suppression function and evoking anti-tumor immune responses. However, there is no consensus that Sorcin promotes HCC progression by regulating pyroptosis. Our study manifested that Sorcin was considerably upregulated, whereas pyroptosis-associated proteins were significantly decreased in HCC tissues and cells. Sorcin silencing attenuated the proliferation, migration, and invasion of HCC cells. Knockdown of Sorcin activates pyroptosis, and overexpression of Sorcin inhibits pyroptosis, yet has no significant effect on apoptosis, ferroptosis, and autophagy in HCC cells. Furthermore, coimmunoprecipitation and immunofluorescence assays revealed that Sorcin interacted with NLRP3 inflammasome to regulate pyroptosis in HCC cells. Then, the NLRP3 inhibitor MCC950 inhibited the activation of Sorcin knockdown-induced pyroptosis and reversed the effect of Sorcin silencing-induced weakening of malignant biological behavior in HCC. Similarly, suppression of Caspase-1 reversed the inhibitory effect of Sorcin knockdown on the malignant progression of HCC via knockdown of Caspase-1 or the inhibitor VX765. Consistent with the in vitro results, the nude mouse experiment showed that Sorcin knockdown inhibited the growth of HCC by activating pyroptosis, while Caspase-1 knockdown partially restored the growth inhibition caused by Sorcin knockdown. Collectively, high Sorcin expression in HCC negatively regulates pyroptosis by interacting with the NLRP3 inflammasome to promote HCC proliferation, migration, and invasion. The results of this study provide a scientific basis for Sorcin as a new biomarker and potential therapeutic target for HCC.

Combined bulk RNA and single-cell RNA analyses reveal TXNL4A as a new biomarker for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate worldwide. The dysregulation of RNA splicing is a major event leading to the occurrence, progression, and drug resistance of cancer. Therefore, it is important to identify new biomarkers of HCC from the RNA splicing pathway. We performed the differential expression and prognostic analyses of RNA splicing-related genes (RRGs) using The Cancer Genome Atlas-liver hepatocellular carcinoma (LIHC). The International Cancer Genome Consortium (ICGC)-LIHC dataset was used to construct and validate prognostic models, and the PubMed database was used to explore genes in the models to identify new markers. The screened genes were subjected to genomic analyses, including differential, prognostic, enrichment, and immunocorrelation analyses. Single-cell RNA (scRNA) data were used to further validate the immunogenetic relationship. Of 215 RRGs, we identified 75 differentially expressed prognosis-related genes, and a prognostic model incorporating thioredoxin like 4A (TXNL4A) was identified using least absolute shrinkage and selection operator regression analysis. ICGC-LIHC was used as a validation dataset to confirm the validity of the model. PubMed failed to retrieve HCC-related studies on TXNL4A. TXNL4A was highly expressed in most tumors and was associated with HCC survival. Chi-squared analyses indicated that TXNL4A expression positively correlated positively with the clinical features of HCC. Multivariate analyses revealed that high TXNL4A expression was an independent risk factor for HCC. Immunocorrelation and scRNA data analyses indicated that TXNL4A was correlated with CD8 T cell infiltration in HCC. Therefore, we identified a prognostic and immune-related marker for HCC from the RNA splicing pathway.

Molecular and Clinical Features of Hepatocellular Carcinoma in Patients with HBV-HDV Infection.

Hepatitis D virus (HDV) infection affects more than 10 million people worldwide, with an estimated prevalence of nearly 4.5% among HBsAg-positive individuals. Epidemiological studies have shown a significant increase in the prevalence of hepatocellular carcinoma (HCC) in patients with chronic HDV infection compared to those with chronic hepatitis B virus (HBV) mono-infection. Despite the clinical findings, data on molecular oncogenic mechanisms are limited and fragmentary. Moreover, the role of HDV in promoting the development of HCC has so far been controversial, because it is difficult to weigh the respective contributions of the two viruses. In this review, we focused on the direct oncogenic action of HDV, its role in modifying the tumor microenvironment, and the genetic signature of HDV-related HCC, comparing these features with HBV-related HCC.

WD repeat domain 48 promotes hepatocellular carcinoma progression by stabilizing c-Myc.

The role of protein members containing the WD40 repeat domain in many diseases, including cancer, is well documented. However, the role of WD repeat domain 48 (WDR48) in hepatocellular carcinoma (HCC) and its molecular basis remain to be further investigated. In the present study, we report that WDR48 is downregulated in clinical HCC samples and evaluate the relationship between its expression and clinical features of HCC. In vitro experiments showed that WDR48 positively regulated the proliferation, invasion and metastasis of HCC cells and in vivo experiments showed that downregulation of WDR48 significantly inhibited the tumorigenicity of HCC cells. Mechanistically, WDR48 binds to the proto-oncogene transcriptional regulator c-Myc and stabilizes c-Myc expression by mediating its deubiquitination, thereby enhancing cell proliferation and EMT signalling. Our study demonstrates the oncogenic role of WDR48 and suggests that WDR48 can be an important target in HCC.

Comprehensive analysis of complement-associated molecular features in hepatocellular carcinoma.

The complement cascade plays a "complementing" role in human immunity. However, the potential roles of complement system in impacting molecular and clinical features of hepatocellular carcinoma (HCC) remain unclear. In this study, eleven public datasets are analyzed to compare the complement status between normal and cancerous samples based on 18 classical complement-associated genes. The complement scores are constructed to quantify complement signatures of individual tumors. HCC patients in the The Cancer Genome Atlas (TCGA) cohort are focused to perform systematical analyses between complement status and immune infiltration, miRNA expression, DNA methylation, clinicopathological features, and drug response. The results show that the complement scores in normal tissues are dramatically higher than those of tumor tissues. Tumor samples in the TCGA cohort are classified into complement score-low and score-high groups. Pathway analysis reveals that tumor-promoting pathways are typically inhibited in complement score-high group. This study also shows that tumor-killing immune cells, such as CD8 + T cells and natural killer cells are abundant and tumor-suppressing miRNAs are upregulated in complement score-high samples. In addition, we identify that complement scores are negatively correlated with certain clinical features, including pathological grade, clinical-stage, and portal vein invasion. Moreover, various molecular features together with complement scores are found to be correlated with response to anti-cancer drugs. This study provides a comprehensive and multidimensional analysis conducive to understanding the role of complement in cancer.

Prognostic significance of long noncoding RNA HOTAIR in hepatocellular carcinoma: A protocol for systematic review and meta-analysis.

Background:Homeobox transcript antisense intergenic RNA (HOTAIR), a long noncoding RNA, has been reported to associate with the prognosis of patients with hepatocellular carcinoma (HCC) in several studies, however, the definite conclusion has not been obtained for conflicting results across different studies. The aim of this study is to determine the association of HOTAIR expression with overall survival, progression-free survival, and clinical features in HCC.Methods:PubMed, Cochrane Library, and Embase will be comprehensively searched to seek the relevant studies. The studies meeting the inclusion criteria will be included into this systematic review and meta-analysis. A combination of hazard ratio and 95% confidence interval is used to estimate the impact of HOTAIR expression on the overall survival and progression-free survival in HCC. The relationship between HOTAIR expression and clinical features of HCC is evaluated using the odds ratio and 95% confidence interval. The study quality is evaluated with the “risk of bias assessment” tool in Cochrane System Assessment Manual or Newcastle-Ottawa Scale. The subgroup analysis, publication bias, and sensitivity analysis are performed.Results:This study provides a strict and classic protocol for systematic review and meta-analysis to determine the prognostic significance of HOTAIR expression in HCC. The findings of this systematic review and meta-analysis may provide a novel diagnostic indicator and potential therapeutic target of HCC.Ethics and dissemination:This study is only a protocol for systematic review and meta-analysis, and all data used in this study is acquired through published studies. Therefore, the ethical review is not needed for this study.Registration number:INPLASY202230050.

The Protein Kinase Activity of NME7 Activates Wnt/β-Catenin Signaling to Promote One-Carbon Metabolism in Hepatocellular Carcinoma.

Metabolic reprogramming by oncogenic signaling is a hallmark of cancer. Hyperactivation of Wnt/β-catenin signaling has been reported in hepatocellular carcinoma (HCC). However, the mechanisms inducing hyperactivation of Wnt/β-catenin signaling and strategies for targeting this pathway are incompletely understood. In this study, we find nucleoside diphosphate kinase 7 (NME7) to be a positive regulator of Wnt/β-catenin signaling. Upregulation of NME7 positively correlated with the clinical features of HCC. Knockdown of NME7 inhibited HCC growth in vitro and in vivo, whereas overexpression of NME7 cooperated with c-Myc to drive tumorigenesis in a mouse model and to promote the growth of tumor-derived organoids. Mechanistically, NME7 bound and phosphorylated serine 9 of GSK3β to promote β-catenin activation. Furthermore, MTHFD2, the key enzyme in one-carbon metabolism, was a target gene of β-catenin and mediated the effects of NME7. Tumor-derived organoids with NME7 overexpression exhibited increased sensitivity to MTHFD2 inhibition. In addition, expression levels of NME7, β-catenin, and MTHFD2 correlated with each other and with poor prognosis in patients with HCC. Collectively, this study emphasizes the crucial roles of NME7 protein kinase activity in promoting Wnt/β-catenin signaling and one-carbon metabolism, suggesting NME7 and MTHFD2 as potential therapeutic targets for HCC. SIGNIFICANCE: The identification of NME7 as an activator of Wnt/β-catenin signaling and MTHFD2 expression in HCC reveals a mechanism regulating one-carbon metabolism and potential therapeutic strategies for treating this disease.

Hsa_circ_0011385 knockdown represses cell proliferation in hepatocellular carcinoma

Circular RNAs (circRNAs), continuous loops of single-stranded RNA, regulate gene expression during the development of various cancers. However, the function of circRNAs in hepatocellular carcinoma (HCC) is rarely discussed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA levels of circ_0011385, miR-361-3p, and STC2 in 96 pairs of HCC tissues (tumor tissues and adjacent normal tissues), HCC cell lines, and L02 (human normal liver cell line) cells. The relationships between circ_0011385 expression and clinical features of HCC were evaluated. Functional experiments in vitro or in vivo were used to evaluate the biological function of circ_0011385. Bioinformatics analysis was performed to predict miRNAs and mRNAs sponged by circ_0011385. RNA immunoprecipitation (RIP) and dual-luciferase reporter gene assays were used to elucidate the interactions among circ_0011385, miR-361-3p, and STC2 (stanniocalcin 2). ChIP and dual-luciferase reporter gene assays were used to identify the upstream regulator of circ_0011385. High expression of circ_0011385 was observed in HCC tissues and cell lines and was significantly associated with tumor size, TNM stage, and prognosis. In addition, inhibition of circ_0011385 expression prevented the proliferation of HCC cells in vitro and in vivo. Circ_0011385 sponged miR-361-3p, thereby regulating the mRNA expression of STC2. In addition, the transcription of circ_0011385 was regulated by SP3. Circ_0011385 knockdown suppressed cell proliferation and tumor activity in HCC. Circ_0011385 may therefore serve as a new biomarker in the diagnosis and treatment of HCC.

Is left-sided involvement of hepatocellular carcinoma an important preoperative predictive factor of poor outcome?

BackgroundThe tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models.MethodsPatients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors.ResultsThere were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size.ConclusionThe left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma.

MiRNA-15a-3p inhibits the metastasis of hepatocellular carcinoma by interacting with HMOX1.

To uncover the relationship between microRNA-15a-3p (miRNA-15a-3p) level and clinical features of hepatocellular carcinoma (HCC), and to explore the influence of miRNA-15a-3p on metastasis of HCC cells. HCC and paracancerous tissues were surgically resected from 44 HCC patients. Their clinical data and follow-up files were recorded. Differential expressions of miRNA-15a-3p in HCC samples were determined. The relationship between miRNA-15a-3p level and clinical features of HCC patients was analyzed. Changes in proliferative, migratory and invasive potentials in Huh7 and HepG2 cells overexpressing miRNA-15a-3p were examined. The downstream gene of miRNA-15a-3p and its involvement in HCC development were finally explored. MiRNA-15a-3p was downregulated in HCC tissues. High metastasis rate and poor prognosis were observed in HCC patients expressing a low level of miRNA-15a-3p. Overexpression of miRNA-15a-3p attenuated proliferative, migratory and invasive potentials in HCC. Protein levels of HMOX1, CD31, c-Myc, MMP-2 and MMP-9 were downregulated in HCC cells after overexpression of miRNA-15a-3p. HMOX1 was the downstream gene of miRNA-15a-3p, which was upregulated in HCC samples. Highly expressed HMOX1 was unfavorable to the prognosis in HCC. Overexpression of HMOX1 abolished the regulatory effects of miRNA-15a-3p on HCC cell phenotypes. MiRNA-15a-3p is closely linked to lymphatic metastasis, distant metastasis and poor prognosis in HCC. It inhibits the malignant development of HCC by interacting with HMOX1.

FGFR3\u25b37\u20139 promotes tumor progression via the phosphorylation and destabilization of ten-eleven translocation-2 in human hepatocellular carcinoma

Overexpression of fibroblast growth factor receptor 3 (FGFR3) correlates with more severe clinical features of hepatocellular carcinoma (HCC). Our previous study has shown that FGFR3∆7–9, a novel splicing mutation of FGFR3, contributes significantly to HCC malignant character, but the epigenetic mechanism is still elusive. In this study, through mass spectrometry and co-immunoprecipitation studies, we discover a close association between FGFR3∆7–9 and the DNA demethylase Ten-Eleven Translocation-2 (TET2). Unlike other certain types of cancer, mutation of TET2 is rare in HCC. However, activation of FGFR3∆7–9 by FGF1 dramatically shortens TET2 half-life. FGFR3∆7–9, but not wild-type FGFR3, directly interacts with TET2 and phosphorylates TET2 at Y1902 site, leading to the ubiquitination and proteasome-mediated degradation of TET2. Overexpression of a phospho-deficient mutant TET2 (Y1902F) significantly reduces the oncogenic potential of FGFR3∆7–9 in vitro and in vivo. Furthermore, FGFR3∆7–9 significantly enhances HCC cell proliferation through the TET2-PTEN-AKT pathway. Specifically, TET2 offsets the elevation of p-AKT level induced by FGFR3∆7–9 through directly binding to PTEN promoter and increasing 5-hmC. Therefore, through phosphorylation and inhibition of TET2, FGFR3∆7–9 reduces PTEN expression and substantiates AKT activation to stimulate HCC proliferation. Together, this study identifies TET2 as a key regulator of the oncogenic role of FGFR3∆7–9 in HCC carcinogenesis and sheds light on new therapeutic strategies for HCC treatment.

Telomerase reverse transcriptase (TERT) promoter mutation correlated with intratumoral heterogeneity in hepatocellular carcinoma.

Telomerase reverse transcriptase (TERT) promoter mutations are frequently observed in hepatocellular carcinoma (HCC); however, the impact of TERT promoter mutations (TPMs) on clinical features and morphological patterns in HCC remains unresolved. Using DNA extracted from 97 HCCs, correlations between TPM status and both the clinical features of HCC and the immunohistochemically-based subgroups were evaluated. Morphological tumor patterns were semi-quantitatively analyzed using hematoxylin and eosin-stained slides of the whole tumor cross-sectional area. The percentages of tumor area occupied by early, well, moderate and poor histological patterns were calculated as a homogeneity index. TPMs were observed in 53 of 97 (55%) HCCs and were significantly associated with older age (P = 0.018) and HCV-related background (P = 0.048). The biliary/stem cell marker-positive subgroup was less likely to have TPMs (29%) compared to the Wnt/β-catenin signaling marker-positive subgroup (60%). In contrast to TPM-negative HCCs, TPM-positive HCCs clearly exhibited intratumoral morphological heterogeneity (0.800 ± 0.117 vs 0.927 ± 0.096, P < 0.0001), characterized by two or more heterogeneous histological patterns (P < 0.0001) and had more well or early differentiated histological patterns (P = 0.024). Our findings showed that intratumoral heterogeneity was strongly related to TPM-positive HCCs, which established novel roles of TPMs, and may improve our understanding particularly about HCC development and diagnosis.

Clinical features of hepatocellular carcinoma with hepatitis B virus among patients on Nucleos(t) ide analog therapy

BackgroundThe clinical manifestation of hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) varies significantly between patients treated with or without nucleos(t) ide analog (NUC) therapy. To have a better understanding of HCC with HBV, we compared the clinical features of patients with HCC receiving or not receiving NUC therapy.MethodsWe retrospectively reviewed the medical records of 76 patients with HBV-caused HCC who received treatment at the Hunan Provincial Peoples’ Hospital starting from January 1, 2008 to December 31, 2017. They were categorized into two groups, namely, NUC group and non-NUC group, based on whether they had received NUC therapy or not.ResultsThe percentage of liver pain (36.36% vs. 79.07%; p < 0.05) and appetite loss (30.30% vs. 70.27%; p < 0.05) in the NUC group was lower than that in the non-NUC group. We observed a similar trend for the percentage of undetectable HBV-DNA (11.63% vs. 63.64%; p < 0.05) and normal ALT (25.58% vs. 75.76%; p < 0.05) between non-NUC and NUC groups. There were no significant differences between the two groups with respect to TBiL (p = 0.370) and ALB (p = 0.475). The same trend was observed for the proportion of HBeAg negative (p = 0.719) and AFP ≤ 14.65 ng/mL (p = 0.199) in both groups. Single tumor nodule was more common in the NUC group compared to the non-NUC group (66.67% vs. 6.98%; p < 0.05). An opposite trend was observed for portal vein invasion (18.18% vs. 79.07%; p < 0.05) and metastasis (0% vs. 44.19%; p < 0.05).ConclusionsNucleos(t) ide analog therapy exerts a significant impact on the clinical and radiological characteristics of hepatocellular carcinoma with HBV. Patients receiving nucleos(t) ide analog therapy were found to have milder symptoms and fewer radiographic findings.

MicroRNA-548b inhibits proliferation and invasion of hepatocellular carcinoma cells by directly targeting specificity protein 1.

Emerging studies have revealed that microRNAs (miRNAs) are aberrantly expressed in hepatocellular carcinoma (HCC), and the dysregulation of miRNAs exerts crucial roles in the carcinogenesis and development of HCC. Therefore, elucidating the relationship between miRNAs and HCC progression is of great importance to develop novel therapeutic techniques and to improve the prognosis of patients with this malignancy. Recently, miR-548b-3p (miR-548b) has been demonstrated to be a cancer-associated miRNA in tongue squamous cell carcinoma and glioma. However, the expression and function of miR-548b in HCC remain poorly understood. In the present study, it was found that miR-548b is expressed at low levels in HCC tissues and cell lines. Decreased miR-548b expression was found to be positively associated with the clinical features of HCC, including the TNM stage and lymph node metastasis. Functional experiments revealed that upregulation of miR-548b expression decreased proliferation and invasion of HCC cells. Specificity protein 1 (SP1) was verified to be a direct target of miR-548b in HCC cells; as Spearman's correlation analysis identified miR-548b expression to be negatively correlated with that of SP1 expression in HCC tissue specimens. In addition, SP1 inhibition exhibited similar effects as miR-548b overexpression in HCC cells. SP1 reintroduction significantly reversed the suppressive effects of miR-548b upregulation on the proliferation and invasion of HCC cells. In conclusion, the results presented in the present study demonstrated that miR-548b may serve as a tumor suppressive miRNA that inhibits the proliferation and invasion of HCC cells by directly targeting SP1. Consequently, miR-548b can be exploited as a novel therapeutic target for treating patients with HCC in the future, but this needs to be investigated further.

Clinical features of hepatocellular carcinoma in nonalcoholic fatty liver disease patients without advanced fibrosis.

The prevalence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD-HCC) is increasing. Unfortunately, NAFLD frequently develops into HCC without liver cirrhosis. Therefore, we investigated the clinical features of HCC in NAFLD patients without advanced fibrosis. We compared clinical characteristics, survival rates, and recurrence rates between 104 NAFLD-HCC patients diagnosed between January 2000 and December 2016, including 35 without (F0-2) and 69 with advanced fibrosis (F3-F4). Risk factors associated with survival and recurrence were evaluated. In total, 66.3% of those diagnosed had advanced fibrosis, 58.8% in men and 80.5% in women (men vs women, P=0.03). In NAFLD-HCC without advanced fibrosis, tumor size was significantly larger and liver histological activity was lower than those in patients with advanced fibrosis. Survival rates between the two groups did not differ. Among those achieving curative treatment, the recurrence rate was significantly lower in NAFLD-HCC without advanced fibrosis (P<0.01). Risk factors of recurrence were male gender, lower serum albumin, and advanced fibrosis. In men, HCC tended to develop from NAFLD without advanced fibrosis. Although tumor size in NAFLD-HCC without advanced fibrosis is significantly larger, the recurrence rate is significantly lower. Surgical therapy should be strongly considered in these cases.

Clinical features and outcomes of hepatocellular carcinoma in Caucasian cirrhotic patients on long-term analogue therapy for hepatitis B.

Long-term oral nucleos(t)ide analogue (NUC) therapy in hepatitis B virus (HBV)-related compensated cirrhotics prevents clinical decompensation but not hepatocellular carcinoma (HCC) development. To define the clinical features and outcomes of HCC in long-term NUC-treated HBV patients. All HCCs developing between 2005 and 2016 in NUC-treated HBV patients under surveillance were studied, excluding those that occurred within the first 6 months of therapy. Clinical features of HCC, alpha faetoprotein (AFP) patterns and patients' outcome were studied. Seventy-six HCC patients were included. Median age was 67 (40-83) years, 84% males, 96% Caucasian, 95% HBeAg-negative, 96% with undetectable HBV DNA, 83% with normal ALT levels, and 92% with compensated cirrhosis. Median serum AFP levels were 4 (1-3615) ng/mL (>7 ng/mL in 36%). HCC was monofocal in 78%, had a median diameter of 20 (6-57) mm and was in its early stage in 92% which allowed potentially curative treatments in 78% (39% ablation, 28% surgical resection, 11% liver transplantation). Overall, a complete response was obtained in 61 (80%) patients: in 40 after a first-line treatment, in 3 after the second-line treatment, in 2 after the third-line treatment, while 16 underwent liver transplantation (8 as second line). During 45 (7-144) months after HCC diagnosis, 19 patients died, 84% from HCC progression. The median time to recurrence was 20.2 (3-53) months, and the cumulative 5-year liver-related survival was 74%. HCCs developing in patients under long-term NUC treatment were single, small tumours, amenable to curative therapies able to confer excellent 5-year survival rates.

Cyclin-dependent kinase 7 ( CDK7 ) expression in human hepatocellular carcinoma: association with HCC progression, prognosis and cell proliferative capacity

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world and contributes to a high cancer mortality globally. The multistep progression of HCC is highly related to the activation of oncogenes and the deactivation of cancer suppressor genes. The cyclin-dependent kinase 7 ( CDK7 ) gene is responsible for maintaining a normal cell cycle, acting as a gatekeeper, and plays an important part in RNA transcription. Although previous studies demonstrate that CDK7 is highly expressed in multiple cancers and is associated with the progression and prognosis of these cancers, the potential role of CDK7 in HCC still needs to be explored. Methods: Data consisting of CDK7 expression levels, patient phenotypes and their matched survival were acquired from The Cancer Genome Atlas (TCGA) database. The associations of the CDK7 expression level with clinicopathological factors and cell proliferation were analyzed. The HCC transcriptome data in the GEO database were inquired and analyzed using GEO2R. Two representative HCC cell models were built to observe the proliferation capacity of HCC cells when CDK7 expression was inhibited by either sh CDK7 or THZ1. Results: Based on the transcriptome and survival data in the TCGA database, the CDK7 expression level was inversely proportional to the overall survival of the HCC patients (pooled HR =1.51, 95% CI =1.06–2.15). For further investigation, the clinical features of HCC were integrated with the expression level of CDK7 . A high expression of CDK7 was proportional to the survival time of the HCC patients (P=2.38×10 −3 ), the neoplasm histologic grade (P −4 ) and cell proliferation (P −3 ). Moreover, CDK7 expression in the liver tumor was higher than that in non-tumor tissues (t-test =6.04, P=2.27×10 −8 ). For HCC patients, CDK7 expression was higher in the tumor tissues than in the para-carcinoma tissues, based on five GEO datasets (Z score =−6.20, P=5.64×10 −10 ). In the SMMC-7721 and Huh7 cell lines, CDK7 shRNA-transfected cells showed significantly lower capabilities of cell growth and proliferation than those of the shRNA control group after 48 hours of cell culture. Furthermore, the cell proliferation capacity was also inhibited when the SMMC-7721 cells (P=6.47×10 −2 ) or Huh7 cells (P=2.52×10 −2 ) were exposed to THZ1. Conclusions: The CDK7 expression level in HCC is associated with HCC progression, prognosis and the cell proliferation capacity. CDK7 may act as a potential target for HCC, and THZ1 might be a potent medicine for HCC treatment.

Less Fibrotic Burden Differently Affects the Long-Term Outcomes of Hepatocellular Carcinoma after Curative Resection

Background: The clinical features of hepatocellular carcinoma (HCC) differ in patients with and without cirrhosis. Objective: We aimed to investigate the long-term outcomes of noncirrhotic HCC patients after curative resection. Methods: We retrospectively examined 649 consecutive patients with HCC who underwent curative resection from 1996 to 2012; 387 (59.6%) were cirrhotic and 262 (40.4%) were noncirrhotic. Results: The mean age was 54.7 years, and 511 (78.7%) of the study participants were men. The most common cause of HCC was hepatitis B virus (n = 419, 64.6%). Noncirrhotic tumors were larger and more advanced than cirrhotic tumors. However, the noncirrhotic group showed better disease-free survival (DFS) and overall survival (OS) after resection than the cirrhotic group (median 64.0 vs. 56.0 months for OS and 48.0 vs. 31.0 months for DFS, p < 0.05). The predictors for HCC recurrence were cirrhosis, tumor number, portal vein invasion, and major surgery. Conclusions: Noncirrhotic HCC showed better DFS and OS after resection than cirrhotic HCC, although noncirrhotic HCC presented more aggressively.

THU-095 - Clinical features of hepatocellular carcinoma in the elderly in a hepatitis B endemic country – a comparative study of 1430 cases

THU-095 - Clinical features of hepatocellular carcinoma in the elderly in a hepatitis B endemic country – a comparative study of 1430 cases