Edmondson Grade Research Articles

LncRNA POLR2J4 Plays a Biomarker Role in Hepatitis B Virus-Related Hepatocellular Carcinoma Through Regulating miR-214-3p.

Identifying novel therapeutic targets for hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC) has become a key goal in liver cancer research. Even though long non-coding RNAs (lncRNAs) do not code proteins, they could regulate the expression of functional genes and thus mediate disease development. The aim of this study was to estimate the role of lncRNA POLR2J4 (POLR2J4) in the progression of hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) to pinpoint a potential biomarker. This study included 109 patients diagnosed with HBV-positive HCC, from whom tissue samples were collected. The expression level of POLR2J4 was evaluated by qPCR. The significance of POLR2J4 in HBV-HCC development and prognosis was estimated by Chi-square, Kaplan-Meier, and Cox analysis. In vitro, POLR2J4 was regulated in HBV-HCC cells, and its effect on cell growth and metastasis was assessed by CCK8 and Transwell assay. The interaction between POLR2J4 and miR-214-3p was evaluated through the luciferase reporter and RNA immunoprecipitation assays. In tumor tissues of HBV-HCC patients, there was an observed increase in the expression of POLR2J4. The increase was closely related with patients' presence of cirrhosis and vascular invasion, higher AFP, and advanced Edmondson grade and TNM stage. An upregulation of POLR2J4 predicted a poor prognosis for HBV-HCC patients and served as an independent indicator. In HBV-related HCC cells, silencing POLR2J4 suppressed cell proliferation, migration, and invasion. Furthermore, POLR2J4 negatively regulated miR-214-3p reversing the inhibition of cellular processes. POLR2J4 acted as a prognostic biomarker and a tumor promoter of HBV-HCC by modulating miR-214-3p.

High expression of HM13 correlates with poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has a high mortality rate, and the identification of early prognostic markers is crucial for improving patient outcomes. This study aimed to investigate the correlation between the expression of Histocompatibility Minor 13 (HM13) and the prognosis of HCC patients. HM13 protein expression was assessed in HCC tissues and cells through immunohistochemistry (IHC), quantitative reverse transcription PCR (qRT-PCR), and western blot. The relationship between HM13 expression and clinicopathological data of HCC was evaluated. Bioinformatics analyses, including Gene Expression Omnibus (GEO) database, Gene Expression Profiling Interactive Analysis (GEPIA), and Kaplan-Meier plotter (K-M plotter), were employed to analyze HM13 expression and its association with patient survival. HM13 was significantly overexpressed in HCC tissues and cells compared to normal controls. IHC revealed that HM13 protein was primarily localized in the cytoplasm and highly expressed in HCC tissues. Interestingly, patients with high HM13 expression had significantly poorer overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS) than those with low expression. HM13 expression was associated with Edmondson grade, metastasis, microvascular invasion, and alpha-fetoprotein (AFP) levels. Multivariate analysis identified HM13 as an independent prognostic factor for poor OS in HCC. HM13 was markedly overexpressed in HCC and correlated with poor prognosis, suggesting its potential as a promising biomarker for early prognostic detection in HCC patients.

Surgical treatment and prognosis analysis of hilar cholangiocarcinoma

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Comparison between laparoscopic liver resection and open liver resection in patients with hepatocellular carcinoma with portal vein tumor thrombosis.

Recently, the outcomes of surgical treatment for advanced hepatocellular carcinoma (HCC) have improved. However, despite the technical advancements in laparoscopic liver resection (LLR), it is still not recommended as the standard treatment for HCC with portal vein tumor thrombosis (PVTT) because of the poor oncological outcomes. This study aims to compare the clinical outcomes of open liver resection (OLR) and LLR in patients with HCC with PVTT. A total of 86 patients with PVTT confirmed in the pathological report between January 2014 and December 2018, were enrolled. Short-term, postoperative, and long-term outcomes, including recurrence-free survival and overall survival rates, were evaluated. No difference between the two groups, except for age, was detected. The median age in the laparoscopic group was significantly higher than that in the open group. Regarding the pathological features, the maximal tumor size was significantly larger in the OLR; other pathological factors did not differ. There was no significant difference between overall survival (OS) and recurrence-free survival (RFS). Vp3 PVTT (hazards ratio [HR] 6.1, 95% confidence interval [CI] 1.9-18.5), Edmondson grade IV (HR 4.7, 95% CI 1.7-12.9, p = 0.003), and intrahepatic metastasis (HR 3.9, 95% CI 2.1-7.2, p < 0.001) remained the unique independent predictors of recurrence-free survival according to a multivariate Cox proportional hazard regression analysis. Laparoscopic liver resection for the management of HCC with PVTT provides the same short- and long-term results as those of the open approach.

Lycorine inhibits migration and proliferation of hepatocellular carcinoma cells by reducing transketonase expression.

Background: Previous studies have showed that lycorine can restrain the development of multiple tumor types, containing hepatocellular carcinoma (HCC), but the underlying mechanisms remain unknown. Methods: We assessed the impact of lycorine on hepatocellular cancer cell proliferation, migration, colony formation, cell cycle, and apoptosis. The possible inhibitory effect of lycorine on the activity of HCC cells was analyzed by RNA-seq, and transketolase (TKT) expression in HCC and nontumorous tissues was detected using RT-PCR. The expression of TKT protein in HCC and tumor adjacent non-cancerous tissues was detected by immunohistochemistry. We evaluated the association of expression of TKT in HCC tissues with prognosis, and investigated the inhibitory effect of lycorine on tumor growth in vivo. Results: Lycorine significantly inhibited the proliferation, invasion, migration, colony formation, cell cycle of HCC cells, but had no obvious impact on apoptosis. Twenty-eight genes were found to be down-regulated in HuH7 and HepG2 cells after lycorine treatment, and the difference of TKT gene expression was significantly. The expression of TKT protein was significantly higher in HCC than in non-tumorous tissues. The expression of TKT was correlated with tumor size, Edmondson grade, AFP, and overall survival. Survival analysis suggested that high expression of TKT was associated with a poor survival. The average tumor volume and weight were significantly reduced in the lycorine injection group, but the body weights of the mice did not change significantly. Conclusion: Lycorine can restrict the migration and proliferation of HCC cells by down-regulating TKT expression, and it may be a potential meaningful drug for the prevention and treatment of HCC.

Upregulation of MED7 was associated with progression in hepatocellular carcinoma.

MED subunits have been reported to be associated with various types of tumors, however, the potential role of MED7 in hepatocellular carcinoma (HCC) was still unclear. The aim of the study was to explore the role of MED7 in HCC. In this study, MED7 mRNA expression levels between HCC and adjacent normal tissues were first analyzed by several public datasets. Then we utilized a tissue microarray (TMA) to investigate the clinical role of MED7 in HCC by immunohistochemistry (IHC). Meanwhile, the potential mechanisms of MED7 based on gene-gene correlation analyses were also explored. High mRNA level of MED7 correlated with advanced stage and worse grade of differentiation. IHC results showed that MED7 protein level was upregulated in HCC and associated with Edmondson grade and Microvascular invasion in 330 cases of HCC. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis revealed that MED7 co-expressed genes participate primarily in ribonucleoprotein complex biogenesis, protein targeting, mRNA processing and nucleoside triphosphate metabolic process et cetera. Further analysis also revealed that MED7 mRNA level has significant correlation with immune cells infiltration levels. MED7 was upregulated in HCC and correlated with progression of HCC. Meanwhile, MED7 may promote HCC through participating in multiple gene networks to influence tumorigenesis as well as immune response in HCC microenvironment.

Association of hypoxia-inducible factor 1α expression with susceptibility to hepatitis B virus-related hepatocellular carcinoma: A meta-analysis.

Hypoxia-inducible factor 1α (HIF-1α) triggers tumorigenesis and progression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Inconsistent findings have been reported on the influence of HIF-1α over-expression on the clinical outcomes of HBV-related HCC. This study aims to clarify the role of HIF-1α overexpression in the tumorigenesis and prognosis of HBV-induced HCC. Systematic and comprehensive search of online papers was carried out to elucidate the contribution of HIF-1α expression to susceptibility of HBV-induced HCC. STATA 12.0 software was utilized to analyze available data extracted from all eligible literature. Publication bias and sensitivity were comprehensively analyzed. A total of 23 published studies involving 2244 subjects were finally screened. The HIF-1α expression was remarkably upregulated in HBV-induced HCC tissues than in normal liver tissues, non-tumorous tissues, paraneoplastic tissues, and non-HBV HCC tissues. The high HIF-1α expression tended to be positively related to capsular infiltration (odds ratio (OR) 1.767; 95% confidence interval (CI) 1.058, 2.950). The HIF-1α expression was relevant to lymph node metastasis (OR 3.778; 95% CI 1.666, 8.568). High levels of HIF-1α expression tended to be closely implicated in portal vein invasion (OR 6.728, 95% CI 2.191, 20.656) but were irrelevant to alpha-fetoprotein, cirrhosis, Edmondson grading, tumor size, age, gender, and histological grade. Analysis of pooled data showed that HIF-1α was not statistically relevant to poor overall survival in HBV-related HCC. Our data provides compelling evidence that HIF-1α overexpression may imply a greater probability of invasion and metastasis in patients with HBV-induced HCC.

Beta2-Microglobulin as Predictive Biomarkers in the Prognosis of Hepatocellular Carcinoma and Development of a New Nomogram.

Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients' post-resection prognosis. We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α1MG) and Beta2-microglobulin (β2MG). Kaplan-Meier analysis assessed microglobulin's impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade. Patients with high β2MG (≥2.395mg/L) had worse overall survival (OS). The nomogram integrated β2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram's discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility. Our β2MG-based nomogram accurately predicts HCC patients' post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma.

The aim of this investigation is to evaluate the association and potential mechanism between plasminogen activator urokinase (PLAU) and the prognosis of patients with liver hepatocellular carcinoma (LIHC). We verified PLAU expression and its correlation with LIHC patients' prognosis in The Cancer Genome Atlas (TCGA) database. The interaction network for protein-gene was established in the GeneMania database and the STRING database, and the association between PLAU and immune cells was assessed in Tumor Immune Estimation Resource (TIMER) and TCGA databases. The potential physiological mechanism was elucidated by the Gene Set Enrichment Analysis (GSEA) enrichment assessment. Finally, the individual clinical data of 100 LIHC patients were retrospectively evaluated to further analyze the clinical value of PLAU. The PLAU expression in LIHC tissues was greater than in paracancerous tissues, and LIHC patients with low PLAU expression had better disease-specific survival (DSS), overall survival (OS), and progression free interval (PFI) than those with high PLAU expression. In the TIMER database, the PLAU expression was positively associated with six kinds of infiltrating immune cells: CD4+ T, neutrophils, CD8+ T, macrophages, B, and dendritic cells, while GSEA enrichment analysis indicated PLAU may impact the biological activities of LIHC by taking part in MAPK and JAK_STAT signaling pathways, angiogenesis, and P53. There were statistically significant differences in T-stage and Edmondson grading between the two groups of patients with high and low expression of PLAU (P<0.05). The tumor progression rates were 88% (44/50) and 92% (46/50) respectively in the low and high PLAU groups, with early recurrence rates of 60% (30/50) and 72% (36/50), and median PFS of 29.5 and 23 months, respectively. The COX regression analysis showed PLAU expression and CS and Barcelona Clinic Liver Cancer (BCLC) stages were independent prognostic factors affecting tumor progression in LIHC patients. The decreased expression of PLAU can prolong the DSS, OS, and PFI in LIHC patients, and can be utilized as a novel predictive index. PLAU combined with CS staging and BCLC staging has good clinical value in the early screening and prognosis of LIHC. These results reveal an efficient approach for developing anticancer strategies against LIHC.

Inflammation-Related Marker NrLR Predicts Prognosis in AFP-Negative HCC Patients After Curative Resection.

The role of inflammation-related markers in alpha-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) is not well known. This study aimed to investigate the clinical significance of inflammation-related markers in AFP-negative HCC patients after curative resection. One thousand one hundred and seventy-nine AFP-negative HCC patients after curative resection were included. Survival rate and prognostic analysis were performed using Kaplan-Meier and Cox regression analysis. Propensity score matching (PSM) was used for patient selection. Multivariate Cox regression showed that neutrophil times γ-glutamyl transpeptidase to lymphocyte ratio (NrLR) was the independent risk factor associated with OS (p = 0.002) and RFS (p = 0.017). Low NrLR groups (n = 628) had lower rates of albumin-bilirubin (ALBI) grade 2 (p < 0.001), lower rates of bleeding and blood transfusion (p < 0.001) than high NrLR groups. Considering tumor features, low NrLR groups had lower AFP levels (p < 0.001), smaller tumor size (p < 0.001), and lower rates of Edmondson grade III-IV (p = 0.024) than high NrLR groups. After PSM, the 1-year, 3 year-, and 5-year OS rates in the low NrLR and high NrLR groups were 96.3%, 86.9%, 64.9%, and 91.4%, 76.7%, 59.5% (p < 0.001), respectively. The 1-year, 3-year, and 5-year RFS rates in the low NrLR and high NrLR groups were 80.0%, 62.9%, 47.5%, and 71.7%, 52.6%, 39.5% (p < 0.001), respectively. NrLR was a poor prognostic factor for mortality and tumor recurrence in AFP-negative HCC patients after curative resection. The simple and low-cost marker could help physician to determine patients at high risk of tumor recurrence for frequent clinical surveillance.

Whole-Transcriptome Sequencing Combined with High-Dimensional Proteomic Technologies Reveals the Potential Value of miR-135b-5p as a Biomarker for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a disease with great heterogeneity and a high mortality rate. It is crucial to identify reliable biomarkers for diagnosis, prognosis, and treatment to improve clinical outcomes in patients with HCC. Alpha-fetoprotein (AFP) is not only a widely used biomarker in clinical practice but also plays a complicated role in HCC, and it has recently been considered to be related to immunotherapy. MicroRNAs (miRNAs) are regarded as key regulators and promising biomarkers of HCC. We investigated the role of an AFP-related miRNA, miR-135b-5p, in HCC progression. Identification of miR-135b-5p was performed based on a cohort of 65 HCC cases and the liver hepatocellular carcinoma cohort of The Cancer Genome Atlas (Asian people only). A combination of whole-transcriptome sequencing and high-dimensional proteomic technologies was used to study the role of miR-135b-5p in HCC. Upregulation of miR-135b-5p was detected in patients with HCC with high serum AFP levels (AFP > 400 ng/ml). Elevated miR-135b-5p expression was associated with adverse prognosis. We also identified the relevance between high miR-135b-5p expression and tumor-related pathological characteristics, such as Edmondson grade and vascular invasion. We revealed tyrosine kinase nonreceptor 1 as a potential target of miR-135b-5p. Additionally, the transcriptional start site of miR-135b-5p had potential binding sites for SRY-box transcription factor 9, and the stemness properties of tumor cells were more remarkable in HCC with the upregulation of miR-135b-5p. The molecular characterization of the miR-135b-5p-high group was similar to that of the HCC subclasses containing moderately and poorly differentiated tumors. Finally, gene signatures associated with improved clinical outcomes in immune checkpoint inhibitor therapy were upregulated in the miR-135b-5p-high group. miR-135b-5p could be a biomarker for predicting the prognosis and antiprogrammed cell death protein 1 monotherapy response in HCC.

The prognosis and clinicopathological significance of histone deacetylase in hepatocellular carcinoma: a meta-analysis.

The value of the different types of HDACs (histone deacetylases) for HCC (hepatocellular carcinoma) prognosis and clinicopathological features is still controversial. Here, we performed a meta-analysis to investigate the possible role of different types of HDACs in HCC. Until October 28, 2021, we have searched the Embase, Cochrane, PubMed, Scopus, Web of Science (WOS), SinoMed, Chinese China National Knowledge Infrastructure (CNKI), Chinese WanFang, and Chinese Weipu databases and evaluated eligible studies according to the criteria. We used hazard ratio (HR) and 95% confidence interval (95% CI) to evaluate the prognostic effects of different types of HDACs on overall survival (OS), disease-free survival (DFS)/recurrence-free survival (RFS) and used odds ratio (OR) and corresponding 95% CI to evaluate the significance of HDACs on clinicopathological characteristics. The I2 statistic and chi-square-based Q test were used to assess the heterogeneity. When the heterogeneity was significant, we conducted a subgroup analysis. In addition, Egger's test and funnel chart were used to assess publication bias. The high expression of class I HDACs was associated with poorer OS, DFS/RFS and differentiation, intrahepatic metastasis, tumor-node-metastasis (TNM), tumor number, tumor size, vascular invasion, and other poor clinicopathological characteristics. The high expression of class II HDACs was related to poor OS and multiple and larger tumors. After subgroup analysis, class II HDACs may also be related to worse TNM and Edmondson grading. The high expression of class III HDACs was related to poor OS, hepatitis B, liver cirrhosis, serum AFP, and vascular invasion. But it was more common in women and was related to single, smaller tumors. Type I, II, and III HDACs are associated with poor prognosis, and there are also correlations with some clinicopathological features, suggesting that different types of HDACs may be valuable biomarkers for HCC.

BCAT1, as a prognostic factor for HCC, can promote the development of liver cancer through activation of the AKT signaling pathway and EMT.

More and more studies have shown that Branched chain amino acid transaminase 1 (BCAT1) is involved in the occurrence and development of a variety of tumors. However, the mechanism of its occurrence and development in hepatocellular carcinoma (HCC) remains unclear.Here, we demonstrated the relationship between BCAT1 and AKT signaling pathway, as well as EMT, and the clinical significance of BCAT1 by using BCAT1 expression in 5 cell lines and 113 liver cancer and non-liver cancer tissue samples.The results showed that the expression of AKT was positively correlated with BCAT1 in HCC tissues, and BCAT1 could promote the progression of HCC cells through the AKT signaling pathway. Clinical analysis and Bioinformatics technology analysis revealed that BCAT1 was correlated with poor prognosis, and BCAT1 expression in the HCC tissues was evidently correlated with tumor number, vascular invasion, Edmondson grade and TNM stage (P < 0.05).In vitro studies showed that BCAT1 increased the invasion and migration of in MHCC-97H cells a d Huh7 cells. By inhibiting the expression of the BCAT1 gene, we detected the corresponding changes in the expression levels of Twist, E-cadherin and Vimentin, confirming that BCAT1 may promote the invasion and migration of HCC cells through epithelial-mesenchymal transformation (EMT). Overall, BCAT1 can activate AKT signaling pathway and EMT to promote the development and metastasis of HCC cells. this study may provide new ideas and directions for cancer diagnosis and treatment.

Role of STX6 as a prognostic factor associated with immune infiltration in hepatocellular carcinoma.

Syntaxin 6 (STX6), a soluble N-ethylmaleimide-sensitive factor-activating receptor protein, has formed an increasing part of cancer research. However, to the best of our knowledge, the role of STX6 in hepatocellular carcinoma (HCC) is still unclear. In the present study, data from multiple bioinformatics databases, including The Cancer Genome Atlas, Gene Expression Omnibus, Kaplan-Meier plotter, Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Integrative Analysis (GEPIA2), and immunohistochemistry (IHC) were utilized to assess the role of STX6 in HCC. The results demonstrated that STX6 expression was upregulated in HCC tissues compared with normal tissues. STX6 expression was significantly associated with tumor size, Edmondson grade and α-fetoprotein (AFP) level. Furthermore, survival analysis demonstrated that high STX6 expression was significantly associated with poor prognosis in patients with HCC. Furthermore, assessment of the immune infiltrates demonstrated that CD163 expression was positively correlated with the STX6 level when analyzed using the TIMER and GEPIA2 databases. IHC results further demonstrated this association. Furthermore, compared with the typically used AFP, STX6 could have an improved diagnostic value in the diagnosis of HCC. In conclusion, STX6 expression was not only positively associated with poor prognosis but may also be involved in the immune inflammatory reaction in HCC. STX6 may become a potential therapeutic and diagnosis maker for patients with HCC.

CT-Based Radiomics Nomogram Improves Risk Stratification and Prediction of Early Recurrence in Hepatocellular Carcinoma After Partial Hepatectomy.

ObjectivesTo develop and validate an intuitive computed tomography (CT)-based radiomics nomogram for the prediction and risk stratification of early recurrence (ER) in hepatocellular carcinoma (HCC) patients after partial hepatectomy.MethodsA total of 132 HCC patients treated with partial hepatectomy were retrospectively enrolled and assigned to training and test sets. Least absolute shrinkage and selection operator and gradient boosting decision tree were used to extract quantitative radiomics features from preoperative contrast-enhanced CT images of the HCC patients. The radiomics features with predictive value for ER were used, either alone or in combination with other predictive features, to construct predictive models. The best performing model was then selected to develop an intuitive, simple-to-use nomogram, and its performance in the prediction and risk stratification of ER was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA).ResultsThe radiomics model based on the radiomics score (Rad-score) achieved AUCs of 0.870 and 0.890 in the training and test sets, respectively. Among the six predictive models, the combined model based on the Rad-score, Edmondson grade, and tumor size had the highest AUCs of 0.907 in the training set and 0.948 in the test set and was used to develop an intuitive nomogram. Notably, the calibration curve and DCA for the nomogram showed good calibration and clinical application. Moreover, the risk of ER was significantly different between the high- and low-risk groups stratified by the nomogram (p <0.001).ConclusionsThe CT-based radiomics nomogram developed in this study exhibits outstanding performance for ER prediction and risk stratification. As such, this intuitive nomogram holds promise as a more effective and user-friendly tool in predicting ER for HCC patients after partial hepatectomy.

Nomogram Based on CT Radiomics Features Combined With Clinical Factors to Predict Ki-67 Expression in Hepatocellular Carcinoma.

ObjectivesThe study developed and validated a radiomics nomogram based on a combination of computed tomography (CT) radiomics signature and clinical factors and explored the ability of radiomics for individualized prediction of Ki-67 expression in hepatocellular carcinoma (HCC).MethodsFirst-order, second-order, and high-order radiomics features were extracted from preoperative enhanced CT images of 172 HCC patients, and the radiomics features with predictive value for high Ki-67 expression were extracted to construct the radiomic signature prediction model. Based on the training group, the radiomics nomogram was constructed based on a combination of radiomic signature and clinical factors that showed an independent association with Ki-67 expression. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to verify the performance of the nomogram.ResultsSixteen higher-order radiomic features that were associated with Ki-67 expression were used to construct the radiomics signature (AUC: training group, 0.854; validation group, 0.744). In multivariate logistic regression, alfa-fetoprotein (AFP) and Edmondson grades were identified as independent predictors of Ki-67 expression. Thus, the radiomics signature was combined with AFP and Edmondson grades to construct the radiomics nomogram (AUC: training group, 0.884; validation group, 0.819). The calibration curve and DCA showed good clinical application of the nomogram.ConclusionThe radiomics nomogram developed in this study based on the high-order features of CT images can accurately predict high Ki-67 expression and provide individualized guidance for the treatment and clinical monitoring of HCC patients.

The correlation of fibrinogen-like protein-1 expression with the progression and prognosis of hepatocellular carcinoma

BackgroundFibrinogen-like-protein 1 (FGL1), a member of the fibrinogen-related protein (FREP) family, is a major ligand of the immune inhibitory receptor lymphocyte-activation gene 3 (LAG-3). While FGL1 is strongly implicated in the development and prognosis of a variety of diseases, its role in hepatocellular carcinoma (HCC) is still disputed. Therefore, the role of FGL1 expression in the progression and prognosis of HCC was investigated.Methods and resultsIn the present study, bioinformatics analysis was first used to probe the expression profile of FGL1 in multiple malignant tumor tissues and paired normal tissues, and to explore the possible relationship between FGL1 and prognosis of HCC patients. Thereafter, the expression levels of FGL1 were determined and compared in human HCC cell lines, HCC tissues, peri-tumor tissues and normal liver tissues by western blot analysis. Furthermore, tissue microarrays were used to detect the expression of FGL1 through immunohistochemical staining and to verify whether the FGL1 expression level was associated with clinicopathological features and the prognosis of HCC patients. The results showed that FGL1 was downregulated significantly in most of the HCC cells lines and HCC tissues, corresponding to the results of the bioinformatics and western blot analyses. FGL1 expression level in HCC was found to be correlated to Edmondson grade and metastasis of the HCC. Additionally, high FGL1 expression was associated with better overall survival in HCC patients, suggesting that FGL1 could function as a tumor suppressor.ConclusionsThe expression level of FGL1 can be correlated with the progression and prognosis of HCC, suggesting its potential as a prognostic biomarker.

Outcomes of adolescent and young patients with hepatocellular carcinoma after curative liver resection: a retrospective study

BackgroundThe risk of HCC is documented to be age-related. The outcomes of young HCC patients on postoperative prognosis are not well understood. The study aims to compare the characteristic differences between adolescent and young (AYA) and non-AYA HCC patients.MethodsWe performed a retrospective analysis of the clinical and pathological findings and the survival of 243 HCC patients who underwent operations between 2007 and 2018.ResultsThe AYA group had a higher AFP level and a higher prevalence of family history of HCC or other cancers than the non-AYA group (P < 0.01 and P < 0.05). AYA patients had more unfavorable pathological characteristics including bigger lesion size, microvascular invasion, portal vein invasion, and hepatic capsule invasion. They also had a more unfavorable Edmondson grade and less tumor capsule formation (P < 0.01). Age was an independent predictor of survival in HCC patients. AYA patients had poorer disease-free and overall survival than non-AYA patients did (P < 0.01). Patients under 30 years old had an even poorer disease-free survival than those aged 30–40 (P = 0.047).ConclusionsAYA patients exhibited a higher recurrence rate and disease-related death rate with more unfavorable pathological characteristics. Enhanced follow-up for young HCC patients should be applied.

Analysis of Related Risk Factors of Microvascular Invasion in Hepatocellular Carcinoma.

Objective To forecast the onset of microvascular invasion (MVI) in patients with hepatoma by evaluating the preoperative aspartate aminotransferase-to-platelet ratio index (APRI), alpha-fetoprotein (AFP), neutrophil-to-lymphocyte ratio (NLR), and other clinicopathological data. Methods In this study, we retrospectively analysed the clinical data of 62 patients who received radical surgery for hepa toma from 2019 to 2021. Patients were separated into the MVI-negative group and the MVI-positive group according to the postoperative pathological diagnosis. The relationships between MVI and NLR, APRI, AFP, tumor size, and other clinical data were assessed using the univariate analysis, receiver operating characteristic (ROC) curve, least absolute shrinkage and selection operator (LASSO) analysis, and logistic analysis. Results The ROC curve determined that the cutoff values of NLR, platelet-to-lymphocyte ratio (PLR), and APRI were 1.520, 98, and 0.275, respectively. The univariate analysis showed that the MVI-positive result was associated with five factors: tumor size (χ2 = 10.620, p = 0.001), AFP (χ2 = 10.524, p = 0.001), Edmondson grade (χ2 = 20.736, p < 0.001), NLR (χ2 = 8.744, p = 0.003), and APRI (χ2 = 4.849, p = 0.028). The LASSO analysis indicated that the risk factors were the number of tumors, PLR, APRI, NLR, AFP, Edmondson grade, and tumor size. The multivariate logistic regression analysis showed that NLR ≥ 1.520 (OR 11.119, p = 0.006), APRI ≥ 0.275 (OR 12.515, p = 0.009), AFP ≥ 200 μg/mL (OR 7.823, p = 0.016), and tumor size > 3 cm (OR 7.689, p = 0.022) were independent risk factors for MVI in patients with hepatoma. Conclusion Preoperative NLR, APRI, AFP, and tumor size are reliable indicators for predicting the appearance of MVI in patients with hepatoma and are of great value in making detailed and reliable treatment protocols for these patients before surgery.

Associations of DDX60L With the Clinical Features and Prognosis of Hepatocellular Carcinoma.

ObjectiveAlthough the pathogenesis of hepatocellular carcinoma (HCC) is still unclear, hepatitis C virus (HCV) infection is considered a common cause of HCC. It has been reported that DDX60L can inhibit HCV replication, but its role in HCC is still poorly understood.MethodsThe expression levels of DDX60L in HCC tissues and in tissues adjacent to the tumor and their correlation with the clinicopathological features of patients were analyzed. We also used Kaplan–Meier curves of overall survival (OS) with Cox regression analysis and log-rank test to investigate the prognostic value of DDX60L in HCC. We further performed cell proliferation, Transwell, and wound healing assays to elucidate the role of DDX60L in HCC using the siRNA-DDX60L Hep3B or HCCLM3 cell line.ResultsUnivariate analysis showed that sex, Edmondson grade, microvascular invasion, tumor stage (III–IV/I–II), AFP, and DDX60L expression were strongly associated with the prognosis of HCC patients. The results of multivariate analysis further suggested that DDX60L might be an independent prognostic factor for OS in patients with HCC (Pmoderate/low = 0.015, Phigh/low = 0.011). The low DDX60L expression in HCC patients with no-metastasis, age ≥55 years, tumor size <5 cm, Edmondson grade = I–II, microvascular invasion, no cirrhosis, HBV positivity, tumor stage = III–IV, AFP >20 μg/L, and multiple tumor was associated with poorer prognosis (P <0.05). Moreover, the expression of DDX60L was significantly lower in HCC samples (N = 285) than in the normal tissues adjacent to the tumor (N = 167, P <0.001). There were no HCV-related HCC patients in this study. Additionally, we found that DDX60L knockdown can promote the proliferation of Hep3B cells, migration and invasion ability of Hep3B and HCCLM3 cells.ConclusionWe found that the downregulation of DDX60L expression correlated with poor prognosis in patients with HCC, which may be independent of the HCV-related pathway. Furthermore, DDX60L significantly inhibited the proliferation of Hep3B cells, migration and invasion of Hep3B and HCCLM3 cells. Therefore, DDX60L can serve as a prognostic biomarker and therapeutic target for HCC.