Early Recurrence In Hepatocellular Carcinoma Patients Research Articles

Prediction power of radiomics in early recurrence of hepatocellular carcinoma: A systematic review and meta-analysis.

Raiomics is an emerging auxiliary diagnostic tool, but there are still differences in whether it can be applied to predict early recurrence of hepatocellular carcinoma (HCC). The purpose of this meta-analysis was to systematically evaluate the predictive power of radiomics in the early recurrence (ER) of HCC. Comprehensive studies on the application of radiomics to predict ER in HCC patients after hepatectomy or curative ablation were systematically screened in Embase, PubMed, and Web of Science. Ten studies which is involving a total of 1929 patients were reviewed. The overall estimates of radiomic models for sensitivity and specificity in predicting the ER of HCC were 0.79 (95% confidence interval [CI]: 0.68-0.87) and 0.83 (95% CI: 0.73-0.90), respectively. The area under the summary receiver operating characteristic curve (SROC) was 0.88 (95% CI: 0.85-0.91). The imaging method is a reliable method for diagnosing HCC. Radiomics, which is based on medical imaging, has excellent power in predicting the ER of HCC. With the help of radiomics, we can predict the recurrence of HCC after surgery more effectively and provide a useful reference for clinical practice.

Prognostic value of tertiary lymphoid structures in hepatocellular carcinoma: a meta-analysis and systematic review.

Multiple investigations and scholarly articles have presented compelling evidence indicating that tertiary lymphoid structures (TLS) play a pivotal role in inhibiting and controlling the advancement of tumors. While there is an abundance of information highlighting the importance of TLS in different cancer types, their prognostic significance specifically in hepatocellular carcinoma (HCC) cancers remains unclear. Thus, this meta-analysis aimed to explore the prognostic relevance of TLS in HCC. We conducted a thorough search across four databases, namely Web of Science, PubMed, Embase, and the Cochrane Library, to identify pertinent studies. The search utilized the keywords "tertiary lymphoid structures" and "hepatocellular carcinoma." The primary outcomes of interest encompassed overall survival (OS), recurrence-free survival (RFS), early recurrence, and late recurrence. The statistical effect size for these measures was expressed in terms of hazard ratios (HR). Six studies were incorporated into the analysis. Among them, four studies, encompassing 6 datasets and involving 1490 patients, and three studies, comprising 5 datasets and involving 656 patients, respectively, investigated the correlation between intratumoral and peritumoral TLSs and the prognosis in HCC patients. The meta-analysis revealed that the presence of intratumoral TLSs is linked to longer RFS and reduced early recurrence (HR, 0.60; 95% CI, 0.50-0.67; p <0.001 and HR, 0.49; 95% CI, 0.36-0.65; p <0.001, respectively). However, no significant association was observed with OS and late recurrence. Sensitivity analysis demonstrated the robustness of these findings, and heterogeneities were minimal. Additionally, the meta-analysis did not detect a relationship between peritumoral TLSs and OS or RFS in HCC patients. The presence of intratumoral TLSs is correlated with better RFS and reduced early recurrence in HCC patients. Further investigation is warranted to elucidate the roles of peritumoral TLSs in the prognosis of HCC patients. https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42023466793.

What Imaging Modality Is More Effective in Predicting Early Recurrence of Hepatocellular Carcinoma after Hepatectomy Using Radiomics Analysis: CT or MRI or Both?

Background: It is of great importance to predict the early recurrence (ER) of hepatocellular carcinoma (HCC) after hepatectomy using preoperative imaging modalities. Nevertheless, no comparative studies have been conducted to determine which modality, CT or MRI with radiomics analysis, is more effective. Methods: We retrospectively enrolled 119 HCC patients who underwent preoperative CT and MRI. A total of 3776 CT features and 4720 MRI features were extracted from the whole tumor. The minimum redundancy and maximum relevance algorithm (MRMR) and least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection, then support vector machines (SVMs) were applied for model construction. Multivariable logistic regression analysis was employed to construct combined models that integrate clinical–radiological–pathological (CRP) traits and radscore. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to compare the efficacy of CT, MRI, and CT and MRI models in the test cohort. Results: The CT model and MRI model showed no significant difference in the prediction of ER in HCC patients (p = 0.911). RadiomicsCT&amp;MRI demonstrated a superior predictive performance than either RadiomicsCT or RadiomicsMRI alone (p = 0.032, 0.039). The combined CT and MRI model can significantly stratify patients at high risk of ER (area under the curve (AUC) of 0.951 in the training set and 0.955 in the test set) than the CT model (AUC of 0.894 and 0.784) and the MRI model (AUC of 0.856 and 0.787). DCA demonstrated that the CT and MRI model provided a greater net benefit than the models without radiomics analysis. Conclusions: No significant difference was found in predicting the ER of HCC between CT models and MRI models. However, the multimodal radiomics model derived from CT and MRI can significantly improve the prediction of ER in HCC patients after resection.

Preoperative Nomogram Incorporating Clinical Factors, Serological Markers and LI-RADS MRI Features to Predict Early Recurrence of Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

To develop and validate a preoperative nomogram model that incorporates clinical factors, serological markers and liver imaging reporting and data system (LI-RADS v2018) MRI features for predicting early recurrence (ER) of hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE). One hundred and fourteen patients with HCC who underwent MRI scanning before TACE were enrolled retrospectively and divided into a training cohort (n=80) and a test cohort (n=34). The clinical factors, serological markers and LI-RADS v2018 MRI features associated with ER were determined by univariable and multivariable analyses. A nomogram model predicting ER after TACE was developed, and its discriminatory ability, goodness-of-fit and clinical application were evaluated by receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA), respectively. In total, 74 (64.9%) patients were diagnosed with ER according to the follow-up results. Increased alpha fetoprotein (AFP) levels, larger tumor size, nonsmooth margin, mosaic architecture satellite nodules and corona enhancement were independent predictors associated with ER (p < 0.05). For the established nomogram model that incorporated these six significant predictors, the AUC values were 0.94 (95% CI: 0.89-0.99) and 0.95 (95% CI: 0.88-1.00) for predicting ER after TACE in the training and test cohorts, respectively. The calibration curve and DCA results demonstrate the good goodness-of-fit and clinical benefits of this nomogram. A preoperative nomogram model based on serological markers and LI-RADS v2018 MRI features could adequately predict ER in HCC patients after TACE, which may provide personalized guidance for predicting prognosis.

A Practical Risk Classification of Early Recurrence in Hepatocellular Carcinoma Patients with Microvascular invasion after Hepatectomy: A Decision Tree Analysis.

This study was designed to establish risk classifications for early recurrence in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. The data of 563 HCC patients with MVI after hepatectomy from two hospitals were retrospectively reviewed. Kaplan-Meier curves and Cox proportional hazards regression models were used to analyse early recurrence. The risk classification for early recurrence was established by using classification and regression tree (CART) analysis and validated by using two independent validation cohorts from two hospitals. Multivariate analysis revealed that four indices, namely, infection of chronic viral hepatitis, MVI classification, tumour size, and serum alpha-fetoprotein (AFP), were independent prognostic factors for early recurrence in HCC patients with MVI. By CART analysis, MVI classification and serum AFP became the nodes of a decision tree and 3-stratification classifications that satisfactorily determined the risk of early recurrence were established. The area under the time-dependent receiver operating characteristic curve (AUC) values of the classification for early recurrence at 0.5, 1.0, and 2.0 years were 0.75, 0.73, and 0.71, respectively, which were all significantly higher than three common classic HCC stages (BCLC stage, Chinese stage, and TNM stage). The calibration curves showed good agreement between predictions by classification for early recurrence and actual survival outcomes. These prediction results also were confirmed in the independent internal and external validation cohorts. The 3 stratification classifications enabled satisfactory risk evaluation of early recurrence in HCC patients with MVI after hepatectomy.

720P Integrative genomic analysis of matched primary and recurrent tumors reveals molecular characteristics of hepatocellular carcinoma with short-term recurrence

High incidence of recurrence is a major challenge for the survival of hepatocellular carcinoma (HCC) patients. Few evidences are available to elucidate mechanisms of early recurrence in HCC patients. Exploring the genomic relation and evolutionary patterns between primary and recurrent tumors is important to prevent postoperative recurrence and improve long-term survival of HCC patients.

Cidan Capsule in Combination with Adjuvant Transarterial Chemoembolization Reduces Recurrence Rate after Curative Resection of Hepatocellular Carcinoma: A Multicenter, Randomized Controlled Trial.

To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

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.

MiRNA-124-3p.1 sensitizes hepatocellular carcinoma cells to sorafenib by regulating FOXO3a by targeting AKT2 and SIRT1

As a multikinase inhibitor, sorafenib is commonly used to treat patients with advanced hepatocellular carcinoma (HCC), however, acquired resistance to sorafenib is a major obstacle to the effectiveness of this treatment. Thus, in this study, we investigated the mechanisms underlying sorafenib resistance as well as approaches devised to increase the sensitivity of HCC to sorafenib. We demonstrated that miR-124-3p.1 downregulation is associated with early recurrence in HCC patients who underwent curative surgery and sorafenib resistance in HCC cell lines. Regarding the mechanism of this phenomenon, we identified FOXO3a, an important cellular stress transcriptional factor, as the key factor in the function of miR-124-3p.1 in HCC. We showed that miR-124-3p.1 binds directly to AKT2 and SIRT1 to reduce the levels of these proteins. Furthermore, we showed that AKT2 and SIRT1 phosphorylate and deacetylate FOXO3a. We also found that miR-124-3p.1 maintains the dephosphorylation and acetylation of FOXO3a, leading to the nuclear location of FOXO3a and enhanced sorafenib-induced apoptosis. Moreover, the combination of miR-124-3p.1 mimics and sorafenib significantly enhanced the curative efficacy of sorafenib in a nude mouse HCC xenograft model. Collectively, our data reveal that miR-124-3p.1 represents a predictive indicator of early recurrence and sorafenib sensitivity in HCC. Furthermore, we demonstrate that miR-124-3p.1 enhances the curative efficacy of sorafenib through dual effects on FOXO3a. Thus, the miR-124-3p.1-FOXO3a axis is implicated as a potential target for the diagnosis and treatment of HCC.

Predictors of recurrence in early hepatocellular carcinoma patients treated with surgical resection

AbstractAlthough surgical resection is a curative treatment for early hepatocellular carcinoma (HCC), the incidence of recurrence is still high. The factors associated with HCC recurrence are unclear and deserve investigation. The early HCC patients receiving surgical resection in Taipei Tzu Chi Hospital were enrolled retrospectively. Those with histologically microvascular invasion and largest tumor size &gt;5 cm were excluded. Aggressive recurrence was defined as multiple recurrence (&gt;3), invasion to vessel or extrahepatic metastasis at the first time of recurrence. A total of 125 HCC patients (86 male; mean age 68.74 ± 11.57 year‐old) were included for final analysis. The survival rate was 96%, 91.2%, and 89.6%, at year 1, 3, and 5, respectively. Sixty one (48.8%) patients had HCC recurrence during the median follow‐up duration of 4.4 years. Of them, aggressive recurrence was present in 17 (27.4%) patients. Among patients with recurrent HCC, those with aggressive recurrence had worse survival rates than those without (P = .008). Multifocal tumor was the predictor associated with HCC recurrence using logistic regression analysis; tumor size was associated with earlier recurrence in aggressive recurrence of HCC using stepwise method (P = .042). Although early HCC patients had satisfactory 5‐year survival rates after surgical resection, the incidence of HCC recurrence was still high. The presence of aggressive recurrence had a negative impact on overall survival. Multifocal tumor in histology has higher risk of HCC recurrence, but not the pathologic grade of differentiation. Tumor size was associated with early recurrence in HCC patients with aggressive recurrence.

Peritumoral Dilation Radiomics of Gadoxetate Disodium-Enhanced MRI Excellently Predicts Early Recurrence of Hepatocellular Carcinoma without Macrovascular Invasion After Hepatectomy.

BackgroundWhether peritumoral dilation radiomics can excellently predict early recrudescence (≤2 years) in hepatocellular carcinoma (HCC) remains unclear.MethodsBetween March 2012 and June 2018, 323 pathologically confirmed HCC patients without macrovascular invasion, who underwent liver resection and preoperative gadoxetate disodium (Gd-EOB-DTPA) MRI, were consecutively recruited into this study. Multivariate logistic regression identified independent clinicoradiologic predictors of 2-year recrudescence. Peritumoral dilation (tumor and peritumoral zones within 1cm) radiomics extracted features from 7-sequence images for modeling and achieved average but robust predictive performance through 5-fold cross validation. Independent clinicoradiologic predictors were then incorporated with the radiomics model for constructing a comprehensive nomogram. The predictive discrimination was quantified with the area under the receiver operating characteristic curve (AUC) and net reclassification improvement (NRI).ResultsWith the median recurrence-free survival (RFS) reaching 60.43 months, 28.2% (91/323) and 16.4% (53/323) patients suffered from early and delay relapse, respectively. Microvascular invasion, tumor size >5 cm, alanine aminotransferase >50 U/L, γ-glutamyltransferase >60 U/L, prealbumin ≤250 mg/L, and peritumoral enhancement independently impaired 2-year RFS in the clinicoradiologic model with AUC of 0.694 (95% CI 0.628–0.760). Nevertheless, these indexes were paucity of robustness (P >0.05) when integrating with 38 most recurrence-related radiomics signatures for developing the comprehensive nomogram. The peritumoral dilation radiomics—the ultimate prediction model yielded satisfactory mean AUCs (training cohort: 0.939, 95% CI 0.908–0.973; validation cohort: 0.842, 95% CI 0.736–0.951) after 5-fold cross validation and fitted well with the actual relapse status in the calibration curve. Besides, our radiomics model obtained the best clinical net benefits, with significant improvements of NRI (35.9%-66.1%, P <0.001) versus five clinical algorithms: the clinicoradiologic model, the tumor-node-metastasis classification, the Barcelona Clinic Liver Cancer stage, the preoperative and postoperative risks of Early Recurrence After Surgery for Liver tumor.ConclusionGd-EOB-DTPA MRI-based peritumoral dilation radiomics is a potential preoperative biomarker for early recurrence of HCC patients without macrovascular invasion.

Development of Prognostic Evaluation Model to Predict the Overall Survival and Early Recurrence of Hepatocellular Carcinoma.

BackgroundThe aberrant expressions of lncRNAs have been frequently demonstrated to be closely associated with the prognosis of patients in many cancer types including hepatocellular carcinoma (HCC). Integration of these lncRNAs might provide accurate evaluation of HCC. Therefore, this study aims to develop a novel prognostic evaluation model based on the expression of lncRNAs to predict the survival of HCC patients, postoperatively.Patients and MethodsRNA sequencing (RNA-seq) analysis was performed for 61 HCC patients (training cohort) to screen prognosis-associated lncRNAs with univariate Cox regression and Log rank test analyses. Multivariate Cox regression analysis was then applied to establish the final model, which was further verified in a validation cohort (n=191). Moreover, performance of the mode was assessed with time-dependent receiver operating characteristic curve (tdROC), Harrell’s c-index, and Gönen & Heller’s K.ResultsAfter a serial statistical computation, a novel risk scoring model consisting of four lncRNAs and TNM staging was established, which could successfully divide the HCC patients into low-risk and high-risk groups with significantly different OS and RFS in both training and validation cohorts. tdROC analysis showed that this model achieved a high performance in predicting OS and 2-year RFS in both cohorts. Gene Set Enrichment Analysis revealed that HCC tumor tissues with high-risk score have stronger capacities in immune escape and resistance to treatment.ConclusionWe successfully established a novel prognostic evaluation model, which exhibited reliable capacity in predicting the OS and early recurrence of HCC patients with relatively higher accuracy.

TSC2 Mutations Were Associated with the Early Recurrence of Patients with HCC Underwent Hepatectomy.

PurposeTo explore the value of Tuberous sclerosis complex 2 (TSC2) mutations in evaluating the early recurrence of hepatocellular carcinoma (HCC) patients underwent hepatectomy.Patients and MethodsA total of 183 HCC patients were enrolled. Next-generation sequencing was performed on tumor tissues to analyze genomic alterations, tumor mutational burden and variant allele fraction (VAF). The associations between TSC2 mutations and recurrence rate within 1 year, RFS and OS after hepatectomy were analyzed.ResultsOur results showed that TSC2 mutation frequency in HCC was 12.6%. Compared to patients without TSC2 mutation, the proportion of microvascular invasion (MVI) and Edmondson grade III–IV was significantly higher in patients with a TSC2 mutation (p<0.05). The VAF of mutated TSC2 was higher in patients with maximum diameter of tumor >5cm or MVI than that of other patients (p<0.05). The frequency of TP53 mutation was significantly higher in patients with a TSC2 mutation than those without TSC2 mutation (p=0.003). Follow-up analysis showed that patients with a TSC2 mutation had significantly higher recurrence rate within 1 year (p=0.015) and poorer median recurrence-free survival (RFS) (p=0.010) than patients without TSC2 mutation. TSC2 mutations did not significantly affect overall survival of patients (p=0.480). The multivariate analysis results showed that the Barcelona Clinic Liver Cancer (BCLC) B-C stage, TSC2 mutations and preoperative serum alpha-fetoprotein level ≥400μg/L were independently associated with recurrence within 1 year after hepatectomy (HR=8.628, 95% CI: 3.836–19.405, p=0.000; HR=3.885, 95% CI: 1.295–11.653, p=0.015; HR=2.327, 95% CI: 1.018–5.323, p=0.045; respectively), and poorer RFS after hepatectomy (HR=3.070, 95% CI: 1.971–4.783, p=0.000; HR=1.861, 95% CI: 1.061–3.267, p=0.030; HR=1.715, 95% CI: 1.093–2.693, p=0.019; respectively).ConclusionTSC2 mutations were significantly associated with MVI in liver para-carcinoma tissue and Edmondson grade III–IV in patients with HCC and were independently associated with recurrence within 1 year and poorer RFS after hepatectomy. The TSC2 mutation may be a potential predictor for early recurrence in HCC patients underwent hepatectomy.

Tfr-Tfh index: A new predicator for recurrence of hepatocellular carcinoma patients with HBV infection after curative resection

BackgroundT follicular helper (Tfh) cells and T follicular regulatory (Tfr) cells were newly identified as the subsets of cluster of CD4+ T cells. As major components of human immune system, they were found in tumor microenvironment and reported to play vital roles in the progression of cancer. But their clinical significance in Hepatocellular carcinoma (HCC) was not elucidated. Thus, this research aimed to investigate their prognostic value in HCC. Materials and methodsA total of 210 subjects (including 110 HCC patients, 50 chronic hepatitis patients and 50 healthy individuals) were enrolled in the research. Tfh, Tfr cells and Treg cells from peripheral blood were measured by flow cytometry. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic performance of Tfr-Tfh Index (TTI) in early HCC and relapse status. Its further prognostic valve was assessed by Kaplan-Meier survival estimate and log rank tests. ResultsTfh cells, Tfr cells, Treg cells and TTI were all higher in HCC patients than in chronic hepatitis patients and healthy control. TTI was found to have positive correlation with the load of HBV. The AUC of TTI for early HCC and relapse status was better than other clinical indices in HBV positive patients. An optimal cutoff point for the TTI stratified the HCC patients into high (>21.96) and low index (≤21.96) groups. High TTI was significantly correlated with recurrence. Univariate and multivariate analyses revealed TTI could be a predictor for recurrence. Moreover, it retained prognostic performance for patients with lower recurrence risk. ConclusionOur research showed that TTI could be a promising indicator for early recurrence in HCC patients with HBV infection.

Low DMT1 Expression Associates With Increased Oxidative Phosphorylation and Early Recurrence in Hepatocellular Carcinoma

BackgroundDespite a high rate of recurrences, long-term survival can be achieved after the resection of hepatocellular carcinoma (HCC) with effective local treatment. Discovery of adverse prognostic variables to identify patients with high risk of recurrence could improve the management of HCC. Accumulating evidence showing a link between carcinogenesis and increased expression of iron import proteins and intracellular iron prompted us to investigate a role of divalent metal-ion transporter-1 (DMT1) that binds and regulates a variety of divalent metals in HCC. Materials and methodsClinical and gene expression data from RNA seq in 369 HCC patients were obtained from The Cancer Genome Atlas. Disease-free survival was compared between DMT1 high- and low-expressing tumors, and gene set enrichment analysis was conducted. ResultsPatients with lower expression of DMT1 exhibited significantly worse disease-free survival compared with the DMT1 high group (P = 0.044), notably in advanced-stage patients (P = 0.008). DMT1 expression did not differ in etiologies, stages, and differentiation status of HCC. Interestingly, DMT1 expression levels inversely associated with cellular respiratory function in HCC. Furthermore, gene set enrichment analysis revealed that metabolism-related gene sets such as glycolysis, oxidative phosphorylation, and reactive oxygen species pathway were significantly enriched in the DMT1 low-expressing HCC. ConclusionsLow DMT1 expression associates with increased oxidative phosphorylation as well as glycolysis and identifies early recurrence in HCC patients after surgical treatment.

Texture Analysis Based on Preoperative Magnetic Resonance Imaging (MRI) and Conventional MRI Features for Predicting the Early Recurrence of Single Hepatocellular Carcinoma after Hepatectomy

To investigate the value of texture analysis and conventional magnetic resonance imaging (MRI) features for predicting the early recurrence (ER) of single hepatocellular carcinoma (HCC) after hepatectomy. A total of 100 HCC patients were first divided into group A (tumor diameter ≤3 cm) and group B (tumor diameter >3 cm) and then classified into two subgroups with ER or nonearly recurrence. Textural parameters (skewness, kurtosis, uniformity, energy, entropy, and correlation) based on MR images and conventional MRI features were compared between the ER and nonearly recurrence subgroups. Predictive factors for ER were further assessed with multivariate logistic regression analysis. Receiver operating characteristic curve was performed to assess the predictive power. There were 53 patients in group A and 47 patients in group B. On arterial phase analysis, tumors with ER displayed significantly lower uniformity and higher entropy in group A, and higher skewness and entropy in group B. On portal venous phase analysis, tumors with ER had significantly lower kurtosis and energy in group A, and higher entropy in group B. Irregular margin in groups A and B, and arterial peritumoral enhancement and capsule presence in group B were associated with ER. In multivariate logistic regression analysis, uniformity and entropy based on arterial phase images and irregular margin in group A, and skewness and entropy based on arterial phase images and arterial peritumoral enhancement in group B were independent predictors for ER. Entropy displayed higher predictive power for ER. Texture analysis based on preoperative MRI are potential quantitative predictors of ER in HCC patients after hepatectomy, and may provide more information for preoperative treatment decision-making and follow up.

Detection of early recurrence in HCC patients after TACE treatment with plasma cfDNA.

e16146Background: Hepatocellular carcinoma (HCC) is the one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with advanced ...

Downregulation of castor zinc finger 1 predicts poor prognosis and facilitates hepatocellular carcinoma progression via MAPK/ERK signaling

BackgroundCastor zinc finger 1 (CASZ1) plays critical roles in various biological processes and pathologic conditions, including cancer. However, the prognostic importance and biologic functions of CASZ1 in hepatocellular carcinoma (HCC) are still unclear.MethodsqRT-PCR, western blot and immunohistochemistry analyses were used to determine CASZ1 expression in HCC samples and cell lines. The clinical significance of CASZ1 was assessed in two independent study cohorts containing 232 patients with HCC. A series of in vitro and in vivo experiments were performed to explore the role and molecular mechanism of CASZ1 in HCC progression.ResultsHere we report that CASZ1 expression was downregulated in HCC tissues and cell lines. Low CASZ1 expression was closely correlated with aggressive clinicopathological features, poor clinical outcomes and early recurrence of HCC patients. Moreover, overexpression of CASZ1 in HCCLM3 cells significantly inhibited cell proliferation, migration, invasion in vitro and tumor growth and metastasis in vivo, whereas silencing CASZ1 significantly enhanced the above abilities of PLC/PRF/5 cells. Further mechanism study indicated that these phenotypic changes were mediated by MAPK/ERK signaling pathway and involved altered expression of MMP2, MMP9 and cyclinD1. Finally, we proved that CASZ1 exerted its tumor-suppressive effect by directly interacting with RAF1 and reducing the protein stability of RAF1.ConclusionsOur study for the first time demonstrated that CASZ1 is a tumor suppressor in HCC, which may serve as a novel prognostic predictor and therapeutic target for HCC patients.

MiR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a

BackgroundHigh frequency of recurrence is the major cause of the poor outcomes for patients with hepatocellular carcinoma (HCC). microRNA (miR)-182-5p emerged as a high-priority miRNA in HCC and was found to be related to HCC metastasis. Whether the expression of miR-182-5p in tumor tissue correlated with early recurrence in HCC patients underwent curative surgery was unknown.MethodsReal-time PCR (RT-PCR) and in situ hybridization (ISH) were conducted to assess the expression of miR-182-5p in HCC cells and tissues. Cell Counting Kit-8 (CCK-8), transwell assays were performed to detected cells proliferation and migration ability. Flow cytometry assays were used to detect cell apoptosis rate, and xenograft model was employed to study miR-182-5p in HCC growth and lung metastasis. The target of miR-182-5p was validated with a dual-luciferase reporter assay and western blotting. Immunohistochemistry, immumoblotting, and immunoprecipitation were performed to test relative protein expression.ResultsWe showed that high expression of miR-182-5p in tumor tissues correlated with poor prognosis as well as early recurrence in HCC patients underwent curative surgery. miR-182-5p enhanced motility and invasive ability of HCC cells both in vitro and in vivo. miR-182-5p directly targets 3′-UTR of FOXO3a and repressed FOXO3a expression, activating AKT/FOXO3a pathway to promote HCC proliferation. Notably, miR-182-5p activated Wnt/β-catenin signaling by inhibiting the degradation of β-catenin and enhancing the interaction between β-catenin and TCF4 which was mediated by repressed FOXO3a.ConclusionsConsistently, miR-182-5p can be a potential predictor of early recurrence for HCC patients underwent curative surgery, and FOXO3a plays a key mediator in miR-182-5p induced HCC progression.

The Incidence of Early Recurrence After Anatomical Versus Non-Anatomical Liver Resection in Patients with Hepatocellular Carcinoma

<i>Aim:</i> This retrospective study compares the incidence of early recurrence after anatomical versus non-anatomical resection in patients with hepatocellular carcinoma (HCC). <i>Patients and Methods:</i> This retrospective study included 26 patients who had a preoperative diagnosis of a single hepatocellular carcinoma (HCC) and who underwent anatomical and non-anatomical liver resection. The patients were divided into two groups. AR Group; anatomical resection group (n= 12) and NAR Group; Non-anatomical resection group (n = 14). The effect of the type of resection (anatomic vs non-anatomic) on early HCC recurrence was studied in both groups. Other risk factors that might play a role in early tumor recurrence such as the TNM staging, tumor size, vascular invasion, pathologic grading and high AFP values were also evaluated. <i>Results:</i> During the follow up period, 5 patients (41.7 %) from AR Group and 6 patients (42.9 %) from NAR Group developed recurrence. Mean time of recurrence was 13.05 ± 4.63 versus 12.53 ± 4.12 months (p 0.764). The univariate analysis method was used to analyze different epidemiological, clinical and pathological variables and there was no statistically significant risk factor in both groups in terms of recurrence. The mean disease-free survival was calculated for both groups using Kaplan–Meier curve and it was 16.013±2.324 for AR group versus 15.657±2.765 months for NAR group (p: 0.98). The cumulative overall survival proportion at end of research was 59.6% for AR group versus 69.87% for NAR group. The mean overall survival was 17.956±2.254 months for AR group versus 20.876±1.263 for NAR group (p: 0.21). The recurrence rate was 41.7%% in AR group and 42.9% in NAR group (p = 0.951). This suggests that the type of resection did not have an impact on early recurrence in HCC patients undergoing liver resection. <i>Conclusion:</i> This study concluded that recurrence-free and overall survivals after both anatomical and non-anatomical resection were not significantly different from the statistical point of view. Liver resection in cirrhotic patients should be performed with good expertise and should pursue strict selection criteria. Non-Anatomical resection may be more appropriate in cirrhotic patients with small HCC to preserve adequate functioning hepatic parenchyma and to avoid increased postoperative morbidity and mortality.