Hepatocellular carcinoma (HCC) is a global popular malignant tumor, which is difficult to cure, and the current treatment is limited.

To analyze the impacts of stress granule (SG) genes on overall survival (OS), survival time, and prognosis in HCC.

The combined The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC), GSE25097, and GSE36376 datasets were utilized to obtain genetic and clinical information. Optimal hub gene numbers and corresponding coefficients were determined using the Least absolute shrinkage and selection operator model approach, and genes for constructing risk scores and corresponding correlation coefficients were calculated according to multivariate Cox regression, respectively. The prognostic model’s receiver operating characteristic (ROC) curve was produced and plotted utilizing the time ROC software package. Nomogram models were constructed to predict the outcomes at 1, 3, and 5-year OS prognostications with good prediction accuracy.

We identified seven SG genes (DDX1, DKC1, BICC1, HNRNPUL1, CNOT6, DYRK3, CCDC124) having a prognostic significance and developed a risk score model. The findings of Kaplan-Meier analysis indicated that the group with a high risk exhibited significantly reduced OS in comparison with those of the low-risk group (P < 0.001). The nomogram model’s findings indicate a significant enhancement in the accuracy of OS prediction for individuals with HCC in the TCGA-HCC cohort. Gene Ontology and Gene Set Enrichment Analysis suggested that these SGs might be involved in the cell cycle, RNA editing, and other biological processes.

Based on the impact of SG genes on HCC prognosis, in the future, it will be used as a biomarker as well as a unique therapeutic target for the identification and treatment of HCC.

• Stress granule genes
• Hepatocellular carcinoma
• Gastrointestinal neoplasms
• Bioinformatics prognosis
• Prognostic value

• Bioinformatics prognosis
• Gastrointestinal neoplasms
• Hepatocellular carcinoma
• Prognostic value
• Stress granule genes

• HBC
• Hepatocellular carcinoma
• KDM2A
• RANGAP1
• SYVN1

• Humans
• Liver Neoplasms/metabolism
• Liver Neoplasms/virology
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/virology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Hepatitis B virus/metabolism
• Hepatitis B virus/genetics
• Cell Line, Tumor
• Up-Regulation/genetics
• Jumonji Domain-Containing Histone Demethylases/metabolism
• Jumonji Domain-Containing Histone Demethylases/genetics
• Viral Core Proteins/metabolism
• Viral Core Proteins/genetics
• Animals
• Carcinogenesis/genetics
• Carcinogenesis/metabolism
• Mice, Nude
• Male
• Cell Proliferation
• Protein Stability
• Gene Expression Regulation, Neoplastic
• Female
• Cell Movement
• Middle Aged
• F-Box Proteins

• BK20211347 the Natural Science Foundation of Jiangsu Province
• 21KJA310004 the Natural Science Foundation of the Jiangsu Higher Education Institutions
• KC21065 Xuzhou Technology Bureau Foundation
• PAPD a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with poor prognosis. Epithelial–mesenchymal transition (EMT) is crucial for cancer progression and metastasis. Thus, we aimed to construct an EMT-related lncRNA signature for predicting the prognosis of HCC patients.

Cox regression analysis and LASSO regression method were used to build an EMT-related lncRNAs risk signature based on TCGA database. Kaplan-Meier survival analysis was conducted to compare the overall survival (OS) in different risk groups. ROC curves and Cox proportional-hazards analysis were performed to evaluate the performance of the risk signature. RT-qPCR was conducted in HCC cell lines and tissue samples to detect the expression of some lncRNAs in this risk model. Furthermore, a nomogram involving the risk score and clinicopathological features was built and validated with calibration curves and ROC curves. In addition, we explored the association between risk signature and tumor immunity, somatic mutations status, and drugs sensitivity.

Twelve EMT-related lncRNAs were obtained to construct the prognostic risk signature for patients with HCC. The Kaplan-Meier curve analysis revealed that patients in the high-risk group had worse overall survival (OS) than those in low-risk group. ROC curves and Cox regression analysis suggested the risk signature could predict HCC survival exactly and independently. The prognostic value of the risk model was confirmed in the testing and entire groups. We also found AC099850.3 and AC092171.2 were highly expressed in HCC cells and HCC tissues. The nomogram could accurately predict survival probability of HCC patients. Gene set enrichment analysis (GSEA) and gene ontology (GO) analysis showed that cancer-related pathways and cell division activity were enriched in high-risk group. The SNPs showed that the prevalence of TP53 mutations was significantly different between high- and low-risk groups; the TP53 mutations and the high TMB were both associated with a worse prognosis in patients with HCC. We also observed widely associations between risk signature and drugs sensitivity in HCC.

A novel EMT-related lncRNAs risk signature, including 12 lncRNAs, was established and identified in patients with HCC, which can accurately predict the prognosis of HCC patients and may be used to guide individualized treatment in the clinical practice.

The aim of our study was to evaluate the potential of expression and single nucleotide polymorphism of Acyl-CoA binding domain containing 4 (ACBD4) gene as prognosis biomarkers in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after hepatectomy.

HBV-related HCC patients from the First Affiliated Hospital of Guangxi Medical University and GSE14520 were included in the current study, as well as The Cancer Genome Atlas (TCGA) HCC verification cohort. Prognostic analysis and multiple functional enrichment analysis methods were used to evaluate the prognostic value and potential biological functions of the ACBD4 gene in HBV-related HCC.

We found that ACBD4 gene is highly expressed in normal liver tissues and markedly down-regulated in HBV-related HCC tissues. ACBD4 gene was significantly related to overall survival (OS) of HCC in TCGA and GSE14520 cohorts, and patients with low ACBD4 expression were markedly related to poor OS. Rs4986172 was observed as an OS biomarker after hepatectomy in the Guangxi HBV-related HCC cohort. The OS of rs4986172 GG genotype was worse than that of HCC patients with A allele (AA and AG genotypes). Multifunctional enrichment analysis suggested that ACBD4 gene is closely related to the metabolic, peroxisome proliferator-activated receptor and cytochrome P450 pathway. Through connectivity map, we also identified eight compounds that may be used as targeted therapeutic agents for ACBD4 gene in HBV-related HCC; these compounds were scopoletin, alfaxalone, bephenium hydroxynaphthoate, apramycin, 4,5-dianilinophthalimide, DL-thiorphan, aminohippuric acid and quinidine. Immune microenvironment analysis revealed that there were significant differences in immune scores of HBV-related HCC tumor tissues with different ACBD4 expression levels.

Our study reveals that ACBD4 expression and rs4986172 can be serve as biomarkers of OS in HBV-related HCC patients after hepatectomy.

• Hepatocellular carcinoma
• Individualized medicine
• Morphophenotypic classification
• Stem cells

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Hepatocellular
• Female
• Humans
• Liver Neoplasms
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Patient Selection
• Retrospective Studies
• Stem Cells

• classifier
• hepatocellular carcinoma
• immunohistochemistry
• prognosis
• prognostic marker

• Hepatocellular carcinoma
• Long-to-short-axis ratio
• Multifocality
• TP53 mutation

• Hepatocellular carcinoma
• Immunomarkers
• Predicting classifiers
• Prognosis
• Recurrence

Primary liver cancer comprises a diverse group of liver tumors. The heterogeneity of these tumors is seen as one of the obstacles to finding an effective therapy. The Hippo pathway, with its downstream transcriptional co-activator Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), has a decisive role in the carcinogenesis of primary liver cancer. Therefore, we examined the expression pattern of YAP and TAZ in 141 patients with hepatocellular carcinoma keratin 19 positive (HCC K19⁺), hepatocellular carcinoma keratin 19 negative (HCC K19⁻), combined hepatocellular–cholangiocarcinoma carcinoma (cHCC-CCA), or cholangiocarcinoma (CCA). All cHCC-CCA and CCA patients showed high expression levels for YAP and TAZ, while only some patients of the HCC group were positive. Notably, we found that a histoscore of both markers is useful in the challenging diagnosis of cHCC-CCA. In addition, positivity for YAP and TAZ was observed in the hepatocellular and cholangiocellular components of cHCC-CCA, which suggests a single cell origin in cHCC-CCA. Within the K19⁻ HCC group, our results demonstrate that the expression of YAP is a statistically significant predictor of poor prognosis when observed in the cytoplasm. Nuclear expression of TAZ is an even more specific and independent predictor of poor disease-free survival and overall survival of K19⁻ HCC patients. Our results thus identify different levels of YAP/TAZ expression in various liver cancers that can be used for diagnostics.

• CCA
• HCC
• Hepatic progenitor cells
• Keratin 19
• TAZ
• YAP
• cHCC-CCA

Hepatocellular carcinoma (HCC) is one of the most common and fatal cancer in the world. HCC frequently presents with advanced disease, has a high recurrence rate and limited treatment options, which leads to very poor prognosis. This warrants urgent improvement in the diagnosis and treatment. Liver biopsy plays very important role in the diagnosis and prognosis of HCC, but with technical advancements and progression in the field of imaging, clinical guidelines have restricted the role of biopsy to very limited situations. Biopsy also has its own problems of needle tract seeding of tumor, small risk of complications, technical and sampling errors along with interpretative errors. Despite this, tissue analysis is often required because imaging is not always specific, limited expertise and lack of advanced imaging in many centers and limitations of imaging in the diagnosis of small, mixed and other variant forms of HCC. In addition, biopsy confirmation is often required for clinical trials of new drugs and targeted therapies. Tissue biomarkers along with certain morphological features, phenotypes and immune-phenotypes that serve as important prognostic and outcome predictors and as decisive factors for therapy decisions, add to the continuing role of histopathology. Advancements in cancer biology and development of molecular classification of HCC with clinic pathological correlation, lead to discovery of HCC phenotypic surrogates of prognostic and therapeutically significant molecular signatures. Thus tissue characteristics and morphology based correlates of molecular subtypes provide invaluable information for management and prognosis. This review thus focuses on the importance of histopathology and resurgence of role of biopsy in the diagnosis, management and prognostication of HCC.

• Hepatocellular carcinoma
• Biomarker
• Biopsy
• Histopathology
• Immunohistochemistry
• Targeted therapy
• Molecular
• Diagnosis
• Prognosis

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/analysis
• Biopsy/methods
• Biopsy/trends
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Disease Progression
• Hepatectomy
• Humans
• Immunohistochemistry
• Liver/diagnostic imaging
• Liver/pathology
• Liver/surgery
• Liver Neoplasms/diagnosis
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Prognosis
• Survival Analysis
• Treatment Outcome

• hepatectomy
• hepatocellular carcinoma
• prognostic score
• recurrence

AIM: To assess the distribution of proteins coded by genes reported as relevant for the molecular classification of hepatocellular carcinoma (HCC).

METHODS: In this retrospective cross-sectional study, the following clinicopathological data were analyzed in 80 autopsied HCC patients: sex, age, ethnicity, alcohol intake, infection with hepatitis B and/or C virus, infection with human immunodeficiency virus, prior treatment, basic and immediate causes of death, liver weight, presence of cirrhosis, number and size of nodules, gross pattern, histological grade and variants, architectural pattern, invasion of large veins, and presence and location of extrahepatic metastases. The protein products of genes known to be involved in molecular pathogenesis of HCC, including epidermal growth factor receptor (EGFR), MET, keratin 19 (K19), vimentin, beta-catenin, mechanistic target of rapamycin (mTOR), extracellular signaling-related kinase (ERK)1, ERK2, Ki67, cyclin D1, caspase 3 and p53, were detected by immunohistochemistry on tissue microarrays. The expression levels were scored and statistically assessed for correlation with HCC parameters.

RESULTS: Infection with hepatitis C virus was identified in 49% of the 80 autopsy patients, cirrhosis in 90%, advanced tumors in 95%, and extrahepatic metastases in 38%. Expression of K19, p53 and ERK1 correlated to high-grade lesions. Expression of ERK1, nuclear beta-catenin, cyclin D1 and ERK2 correlated to higher rates of cell proliferation as determined by Ki67. Expression of MET, EGFR (> 0) and caspase 3 correlated with lower histological grades. Expression of EGFR correlated to that of caspase 3, and overexpression of EGFR (≥ 200/300) was observed in low-grade tumors more frequently (grades 1 and 2: 67% vs grade 3: 27% and grade 4: 30%). Expression of ERK1 was associated with that of K19 and vimentin, whereas expression of ERK2 was associated with that of cyclin D1, MET and membrane beta-catenin. Expression of vimentin was strongly correlated with that of K19.

CONCLUSION: Expression of K19, p53, ERK1, ERK2, vimentin and nuclear beta-catenin was related to higher-grade markers, as opposed to expression/overexpression of EGFR, MET and caspase 3.

• Hepatocellular carcinoma
• Epidermal growth factor receptor
• Autopsy
• Immunohistochemistry
• Liver
• Classification

• Adult
• Aged
• Aged, 80 and over
• Autopsy
• Brazil
• Carcinoma, Hepatocellular/classification
• Carcinoma, Hepatocellular/epidemiology
• Carcinoma, Hepatocellular/metabolism
• Carcinoma, Hepatocellular/pathology
• Case-Control Studies
• Caspase 3/metabolism
• Cross-Sectional Studies
• Cyclin D1/metabolism
• ErbB Receptors/metabolism
• Female
• HIV Infections/epidemiology
• Hepatitis B, Chronic/epidemiology
• Hepatitis C, Chronic/epidemiology
• Humans
• Immunohistochemistry
• Keratin-19/metabolism
• Ki-67 Antigen/metabolism
• Liver Cirrhosis/epidemiology
• Liver Cirrhosis/pathology
• Liver Neoplasms/classification
• Liver Neoplasms/epidemiology
• Liver Neoplasms/metabolism
• Liver Neoplasms/pathology
• Male
• Middle Aged
• Mitogen-Activated Protein Kinase 1/metabolism
• Mitogen-Activated Protein Kinase 3/metabolism
• Proto-Oncogene Proteins c-met/metabolism
• Retrospective Studies
• TOR Serine-Threonine Kinases/metabolism
• Tissue Array Analysis
• Tumor Suppressor Protein p53/metabolism
• Vimentin/metabolism
• beta Catenin/metabolism

• Colon Cancer
• Histomorphology
• Prognosis
• Risk Stratification
• Stage I/II

• Diagnosis
• Liver cancer
• Molecular pathology
• Treatment model

• Ki-67
• clinicopathological features
• hepatocellular carcinoma (HCC)
• meta-analysis
• prognostic value

• Hepatocellular carcinoma
• Immunohistochemical
• Management
• Predictive marker
• Prognostic marker

• E-cadherin
• gastrointestinal tumours
• vimentin

• cell cycle
• hepatocellular carcinoma
• radiofrequency ablation
• recurrence
• surgery

Total mesorectal excision (TME) remains commonplace for T1–2 rectal cancer owing to fear of undertreating a small proportion of patients with node-positive disease. Molecular stratification may predict cancer progression. It could be used to select patients for organ-preserving surgery if specific biomarkers were validated.

Gene methylation was quantified using bisulphite pyrosequencing in 133 unirradiated rectal cancer TME specimens. KRAS mutation and microsatellite instability status were also defined. Molecular parameters were correlated with histopathological indices of disease progression. Predictive models for nodal metastasis, lymphovascular invasion (LVI) and distant metastasis were constructed using a multilevel reverse logistic regression model.

Methylation of the retinoic acid receptor β gene, RARB, and that of the checkpoint with forkhead and ring finger gene, CHFR, was associated with tumour stage (RARB: 51·9 per cent for T1–2 versus 33·9 per cent for T3–4, P < 0·001; CHFR: 5·5 per cent for T1–2 versus 12·6 per cent for T3–4, P = 0·005). Gene methylation associated with nodal metastasis included RARB (47·1 per cent for N− versus 31·7 per cent for N+; P = 0·008), chemokine ligand 12, CXCL12 (12·3 per cent for N− versus 8·9 per cent for N+; P = 0·021), and death-associated protein kinase 1, DAPK1 (19·3 per cent for N− versus 12·3 per cent for N+; P = 0·022). RARB methylation was also associated with LVI (45·1 per cent for LVI− versus 31·7 per cent for LVI+; P = 0·038). Predictive models for nodal metastasis and LVI achieved sensitivities of 91·1 and 85·0 per cent, and specificities of 55·3 and 45·3 per cent, respectively.

This methylation biomarker panel provides a step towards accurate discrimination of indolent and aggressive rectal cancer subtypes. This could offer an improvement over the current standard of care, whereby fit patients are offered radical surgery. May assist selection for organ preservation

• TP53
• expression
• hepatocellular carcinoma (HCC)
• meta-analysis
• prognosis