• Carcinosarcoma
• Cholangiocarcinoma
• Hepatocellular carcinoma
• Lymph node metastases
• Primary liver cancer
• Stem cells

• Humans
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/therapy
• Cholangiocarcinoma/genetics
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/therapy
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Liver Neoplasms/genetics
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/genetics

• Carcinogenesis
• Combined hepatocellular-cholangiocarcinoma
• Diagnosis
• Liver cancer
• Systemic tumor therapy
• Tumor biology

• Intraoperative bleeding
• Machine learning
• Model
• Primary liver cancer

• Combined hepatocellular carcinoma and cholangiocarcinoma
• Prognosis
• Prognostic factors
• Surgery

• Humans
• Carcinoma, Hepatocellular/pathology
• Disease-Free Survival
• Liver Neoplasms/pathology
• Prognosis
• Bile Duct Neoplasms/pathology
• Cholangiocarcinoma/pathology
• Bile Ducts, Intrahepatic/pathology
• Retrospective Studies

• atezolizumab
• bevacizumab
• case series
• combined hepatocellular-cholangiocarcinoma
• immunotherapy

• combined hepatocellular-cholangiocarcinoma (cHCC-CC)
• liver
• surgical

• ACYP1
• Acylphosphatase 1
• Cholangiocarcinoma
• Combined hepatocellular–intrahepatic cholangiocarcinoma
• Hepatocellular carcinoma
• Primary liver carcinoma

• Humans
• Acid Anhydride Hydrolases/genetics
• Bile Duct Neoplasms/enzymology
• Bile Duct Neoplasms/pathology
• Bile Ducts, Intrahepatic/pathology
• Carcinoma, Hepatocellular/enzymology
• Carcinoma, Hepatocellular/pathology
• Cholangiocarcinoma/enzymology
• Cholangiocarcinoma/pathology
• Liver Neoplasms/enzymology
• Liver Neoplasms/pathology
• Retrospective Studies
• RNA, Small Interfering/genetics
• Acylphosphatase

• Combined hepatocellular and cholangiocarcinoma
• Hepatocellular carcinoma
• Intrahepatic cholangiocarcinoma
• Nomogram
• SEER

• Bile Duct Neoplasms/pathology
• Bile Ducts, Intrahepatic/pathology
• Carcinoma, Hepatocellular/pathology
• Cholangiocarcinoma/pathology
• Humans
• Liver Neoplasms/pathology
• Nomograms
• Prognosis
• Reproducibility of Results
• SEER Program

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare type of primary liver malignancy. Among the risk factors, hepatitis B and hepatitis C virus infections, cirrhosis, and male gender are widely reported. The clinical appearance of cHCC-CCA is similar to that of HCC and iCCA and it is usually silent until advanced states, causing a delay of diagnosis. Diagnosis is mainly based on histology from biopsies or surgical specimens. Correct pre-surgical diagnosis during imaging studies is very problematic and is due to the heterogeneous characteristics of the lesion in imaging, with overlapping features of HCC and CCA. The predominant histological subtype within the lesion establishes the predominant imaging findings. Therefore, in this scenario, the radiological findings characteristic of HCC show an overlap with those of CCA. Since cHCC-CCAs are prevalent in patients at high risk of HCC and there is a risk that these may mimic HCC, it is currently difficult to see a non-invasive diagnosis of HCC. Surgery is the only curative treatment of HCC-CCA. The role of liver transplantation (LT) in the treatment of cHCC-CCA remains controversial, as is the role of ablative or systemic therapies in the treatment of this tumour. These lesions still remain challenging, both in diagnosis and in the treatment phase. Therefore, a pre-treatment imaging diagnosis is essential, as well as the identification of prognostic factors that could stratify the risk of recurrence and the most adequate therapy according to patient characteristics.

• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms/diagnosis
• Bile Duct Neoplasms/genetics
• Bile Duct Neoplasms/immunology
• Bile Duct Neoplasms/therapy
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/immunology
• Carcinoma, Hepatocellular/therapy
• Cholangiocarcinoma/diagnosis
• Cholangiocarcinoma/genetics
• Cholangiocarcinoma/immunology
• Cholangiocarcinoma/therapy
• Female
• Forecasting
• Humans
• Immunotherapy
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics
• Liver Neoplasms/immunology
• Liver Neoplasms/therapy
• Male
• Middle Aged
• Neoplasms, Multiple Primary/diagnosis
• Neoplasms, Multiple Primary/genetics
• Neoplasms, Multiple Primary/immunology
• Neoplasms, Multiple Primary/therapy
• Treatment Outcome

The kynurenine pathway (KP) is a biochemical pathway that synthesizes the vital coenzyme, nicotinamide adenine dinucleotide (NAD⁺). In cancer, the KP is significantly activated, leading to tryptophan depletion and the production of downstream metabolites, which skews the immune response towards tumour tolerance. More specifically, advanced stage cancers that readily metastasize evidence the most dysregulation in KP enzymes, providing a clear link between the KP and cancer morbidity. Consequently, this provides the rationale for an attractive new drug discovery opportunity for adjuvant therapeutics targeting KP-mediated immune tolerance, which would greatly complement current pharmacological interventions. In this review, we summarize recent developments in the roles of the KP and clinical trials examining KP inhibition in liver cancer.

As the second and third leading cancer-related death in men and the world, respectively, primary liver cancer remains a major concern to human health. Despite advances in diagnostic technology, patients with primary liver cancer are often diagnosed at an advanced stage. Treatment options for patients with advanced hepatocarcinoma (HCC) are limited to systemic treatment with multikinase inhibitors and immunotherapy. Furthermore, the 5-year survival rate for these late-stage HCC patients is approximately 12% worldwide. There is an unmet need to identify novel treatment options and/or sensitive blood-based biomarker(s) to detect this cancer at an early stage. Given that the liver harbours the largest proportion of immune cells in the human body, understanding the tumour–immune microenvironment has gained increasing attention as a potential target to treat cancer. The kynurenine pathway (KP) has been proposed to be one of the key mechanisms used by the tumour cells to escape immune surveillance for proliferation and metastasis. In an inflammatory environment such as cancer, the KP is elevated, suppressing local immune cell populations and enhancing tumour growth. In this review, we collectively describe the roles of the KP in cancer and provide information on the latest research into the KP in primary liver cancer.

• IDO inhibitor
• immune evasion
• indoleamine 2,3 dioxygenase 1
• kynurenine pathway
• primary liver cancer
• tryptophan 2,3 dioxygenase 2

• ASF1B
• HCC
• immune infiltration
• lncRNA-miRNA-mRNA network
• recurrence

• biliary tract
• cholangiocarcinoma
• combined hepatocellular cholangiocarcinoma

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis.

The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated.

During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes.

Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

• Combined tumor
• Hepatic
• Hepatocellular carcinoma
• Progenitor cells
• Stem cells

• Cholangiocarcinoma
• Combined tumor
• Hepatic progenitor cell
• Hepatocellular carcinoma
• Stem cell feature

• Biopsy
• Diagnosis
• Liver neoplasm
• Magnetic resonance imaging
• Stem cell

Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) is an infrequent type of primary liver cancer that comprises hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). This study investigated the clinicopathological features and prognosis among cHCC-CC, HCC, and CC groups.

We prospectively collected the data of 608 patients who underwent surgical resection for liver cancer between 2011 and 2018 at E-Da Hospital, I-Shou University, Kaohsiung, Taiwan. Overall, 505 patients with cHCC-CC, HCC, and CC were included, and their clinicopathological features, overall survival (OS), and recurrence were recorded. OS and recurrence rates were analyzed using the Kaplan–Meier analysis.

In the entire cohort, the median age was 61 years and 80% were men. Thirty-five (7.0%) had cHCC-CC, 419 (82.9%) had HCC, and 51 (10.1%) had CC. The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. OS was significantly lower in the cHCC-CC group than in the HCC group but was not significantly higher in the cHCC-CC group than in the CC group. The median OS of cHCC-CC, HCC, and CC groups was 50.1 months [95% confidence interval (CI): 38.7–61.2], 62.3 months (CI: 42.1–72.9), and 36.2 months (CI: 15.4–56.5), respectively. Cumulative OS rates at 1, 3, and 5 years in cHCC-CC, HCC, and CC groups were 88.5%, 62.2%, and 44.0%; 91.2%, 76.1%, and 68.0%; and 72.0%, 48.1%, and 34.5%, respectively. After propensity score matching (PSM), OS in the cHCC-CC group was not significantly different from that in the HCC or CC group. However, OS was significantly higher in the HCC group than in the CC group before and after PSM. Furthermore, the disease-free survival was not significantly different among cHCC-CC, HCC, and CC groups before and after PSM.

The clinicopathological features of the cHCC-CC group were more identical to those of the HCC group than the CC group. The OS rate was significantly lower in the cHCC-CC group than the HCC group. However, after PSM, OS and disease-free survival in the cHCC-CC group were not significantly different from those in the HCC or CC group.

• Combined hepatocellular carcinoma and cholangiocarcinoma
• Overall survival
• Prognosis
• Recurrence

Although elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with survival in some liver cancers, its prognostic relevance has not been studied in the context of combined hepatocellular cholangiocarcinoma CHCC-CC, a rare primary liver cancer. We investigated whether elevated NLR and a predominance of cholangiocarcinoma might predict poor prognosis in patients with resectable CHCC-CC.

We retrospectively reviewed the clinicopathologic data of forty-two patients with CHCC-CC receiving hepatectomies at our hospital. We used Kaplan-Meier and Cox regression to analyze survival.

Two-year disease-free survival and five-year overall survival rates were 43.2% and 32.9%, respectively. Univariate analyses showed that patients with NLR ≥3 had significantly worse 2-year DFS and 5-year OS rates. Univariant Kaplan-Meier survival analysis also associated these rates with a predominance in intrahepatic cholangiocarcinoma, AJCC tumor stage, pathological T stage and lymph-vascular invasion. However, our multivariate analysis found NLR ≥3 to be the only independent predictor of disease recurrence and poorer survival.

Neutrophil-to-lymphocyte ratio was the most important independent predictor of poorer survival in patients with resectable CHCC-CC. Predominance of intrahepatic cholangiocarcinoma, advanced AJCC tumor stage and pathological T stage, and lymph-vascular invasion also may affect poor prognosis in patients receiving complete tumor resections.

• genetic aberrations
• liver transplantation
• loco-regional therapy
• mixed liver cancer
• primary liver cancer

Combined hepatocellular-cholangiocarcinoma (cHCC-ICC) is an uncommon and aggressive form of primary liver cancer. Currently, there are no international guidelines for optimal management. For localized tumors, radical resection represents the preferred treatment option, whereas for advanced tumors, systemic therapies recommended for intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are often selected. Emerging information from comparative cohort studies, genomic and transcriptomic data sets are starting to build a case for rationalized approaches to systemic treatment in the advanced setting specific to cHCC-ICC.

• Combined hepatocellular-cholangiocarcinoma
• biphenotypic
• cHCC-CCA
• cHCC-ICC
• genomics
• primary liver cancer
• systemic therapy

• Cholangiocarcinoma
• Hepatectomy
• Hepatocellular carcinoma
• Hepatocholangiocarcinoma
• Liver neoplasms

• Aged
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/surgery
• Cholangiocarcinoma/mortality
• Cholangiocarcinoma/surgery
• Female
• Hepatectomy
• Humans
• Liver Neoplasms/mortality
• Liver Neoplasms/surgery
• Male
• Middle Aged
• Neoplasms, Multiple Primary
• Survival Rate
• Treatment Outcome

The prognosis of patients with combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma (CHC) is usually poor, and effective adjuvant therapy is missing making it important to investigate whether these patients may benefit from adjuvant transarterial chemoembolization (TACE). We aimed to evaluate the efficiency of adjuvant TACE for long-term recurrence and survival after curative resection before and after propensity score matching (PSM) analysis.

In this retrospective study, of 230 patients who underwent resection for CHC between January 1994 and December 2014, 46 (18.0%) patients received adjuvant TACE. Univariate and multivariate regression analyses were used to identify the independent predictive factors of survival. Cox regression analyses and log-rank tests were used to compare overall survival (OS) and disease-free survival (DFS) between patients who did or did not receive adjuvant TACE.

A total of 230 patients (mean age 52.2 ± 11.9 years; 172 men) were enrolled, and 46 (mean age 52.7 ± 11.1 years; 38 men) patients received TACE. Before PSM, in multivariate regression analysis, γ-glutamyl transpeptidase (γ-GT), tumour nodularity, macrovascular invasion (MVI), lymphoid metastasis, and extrahepatic metastasis were associated with OS. Alanine aminotransferase (ALT), MVI, lymphoid metastasis, and preventive TACE (HR: 2.763, 95% CI: 1.769–4.314, p < 0.001) were independent prognostic factors for DFS. PSM created 46 pairs of patients. Before PSM, adjuvant preventive TACE was not associated with an increased risk of OS (HR: 0.911, 95% CI: 0.545–1.520, p = 0.720) or DFS (HR: 3.345, 95% CI: 1.686–6.638, p = 0.001). After PSM, the 5-year OS and DFS rates were comparable in the TACE group and the non-TACE group (OS: 22.7% vs 14.9%, respectively, p = 0.75; DFS: 11.2% vs 14.4%, respectively, p = 0.06).

The present study identified that adjuvant preventive TACE did not influence DFS or OS after curative resection of CHC.

• Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma
• Disease-free survival
• Overall survival
• Propensity score matching analysis
• Transarterial chemoembolization

• Fibrolamellar carcinoma
• combined hepatocellular-cholangiocarcinoma
• computed tomography
• hepatobiliary contrast agents
• magnetic resonance imaging
• primary hepatic tumors

Hepatocellular carcinoma (HCC) can be diagnosed noninvasively with contrast-enhanced dynamic computed tomography, magnetic resonance imaging, or ultrasonography on the basis of its hallmark imaging features of arterial phase hyperenhancement and washout on portal or delayed phase images. However, approximately 40% of HCCs show atypical imaging features, posing a significant diagnostic challenge for radiologists. Another challenge for radiologists in clinical practice is the presentation of many HCC mimickers such as intrahepatic cholangiocarcinoma, combined HCC-cholangiocarcinoma, arterioportal shunt, and hemangioma in the cirrhotic liver. The differentiation of HCCs from these mimickers on preoperative imaging studies is of critical importance. Hence, we will review the typical and atypical imaging features of HCCs and the imaging features of its common mimickers. In addition, we will discuss how to solve these challenges in practice.

• Atypical hepatocellular carcinoma
• Combined hepatocellular-cholangiocarcinoma
• Hepatocellular carcinoma mimickers
• Intrahepatic mass-forming cholangiocarcinoma
• Liver Imaging Reporting and Data System

To explore which preoperative clinical data and conventional MRI findings may indicate microvascular invasion (MVI) of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) and have clinical significance.

The study enrolled 113 patients with histopathologically confirmed cHCC-CCA (MVI-positive group [n = 56], MVI-negative group [n = 57]). Two radiologists retrospectively assessed the preoperative MRI features (qualitative analysis of morphology and dynamic enhancement features), and each lesion was assigned according to the LI-RADS. Preoperative clinical data were also evaluated. Logistic regression analyses were used to assess the relative value of these parameters as potential predictors of MVI. Recurrence-free survival (RFS) rates after hepatectomy in the two groups were estimated using Kaplan–Meier survival curves and compared using the log-rank test.

The majority of cHCC-CCAs were categorized as LR-M. On multivariate analysis, a higher serum AFP level (OR, 0.523; 95% CI, 0.282–0.971; p = 0.040), intratumoral fat deposition (OR, 14.368; 95% CI, 2.749–75.098; p = 0.002), and irregular arterial peritumoral enhancement (OR, 0.322; 95% CI, 0.164–0.631; p = 0.001) were independent variables associated with the MVI of cHCC-CCA. After hepatectomy, patients with MVI of cHCC-CCA showed earlier recurrence than those without MVI (hazard ratio [HR], 0.402; 95% CI, 0.189–0.854, p = 0.013).

A higher serum AFP level and irregular arterial peritumoral enhancement are potential predictive biomarkers for the MVI of cHCC-CCA, while intratumoral fat detected on MRI suggests a low risk of MVI. Furthermore, cHCC-CCAs with MVI may have worse surgical outcomes with regard to early recurrence than those without MVI.

• Higher serum levels of AFP combined with irregular arterial peritumoral enhancement are independent risk factors for the MVI of cHCC-CCA, while fat deposition might be a protective factor.

• cHCC-CCA with MVI may have a higher risk of early recurrence after surgery.

• Most cHCC-CCAs were categorized as LR-M in this study, and no significant difference was found in MVI based on LI-RADS category.

• Liver neoplasms
• Magnetic resonance imaging
• Neoplasm invasiveness

• Adult
• Aged
• Bile Duct Neoplasms/blood supply
• Bile Duct Neoplasms/diagnostic imaging
• Bile Duct Neoplasms/pathology
• Bile Duct Neoplasms/surgery
• Bile Ducts, Intrahepatic/pathology
• Biomarkers, Tumor/blood
• Carcinoma, Hepatocellular/blood supply
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Cholangiocarcinoma/blood supply
• Cholangiocarcinoma/diagnostic imaging
• Cholangiocarcinoma/pathology
• Cholangiocarcinoma/surgery
• Disease-Free Survival
• Female
• Hepatectomy
• Humans
• Liver Neoplasms/blood supply
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Magnetic Resonance Imaging
• Male
• Microcirculation
• Middle Aged
• Neoplasm Invasiveness
• Neoplasms, Multiple Primary/blood supply
• Neoplasms, Multiple Primary/diagnostic imaging
• Neoplasms, Multiple Primary/pathology
• Neoplasms, Multiple Primary/surgery
• Recurrence
• Retrospective Studies

• National Natural Science Foundation of China
• Shanghai Science and Technology Committee
• Zhongshan Hosiptal, Fudan University
• Shanghai Municipal Key Clinical Specialty

• Combined hepatocellular and cholangiocarcinoma (CHC)
• intrahepatic cholangiocarcinoma (ICC)
• machine learning
• radiomics

• HCC
• ICC
• Recurrence
• Survival
• cHCC-CCA

• Cholangiocarcinoma
• Hepatocellular carcinoma
• Hepatocholangiocarcinoma
• Liver neoplasms

Objective: Our study is aim to explore potential key biomarkers and pathways in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) using genome-wide expression profile dataset and methods.

Methods: Dataset from the GSE14520 is used as the training cohort and The Cancer Genome Atlas dataset as the validation cohort. Differentially expressed genes (DEGs) screening were performed by the limma package. Gene set enrichment analysis (GSEA), weighted gene co-expression network analysis (WGCNA), gene ontology, the Kyoto Encyclopedia of Genes and Genomes, and risk score model were used for pathway and genes identification.

Results: GSEA revealed that several pathways and biological processes are associated with hepatocarcinogenesis, such as the cell cycle, DNA repair, and p53 pathway. A total of 160 DEGs were identified. The enriched functions and pathways of the DEGs included toxic substance decomposition and metabolism processes, and the P450 and p53 pathways. Eleven of the DEGs were identified as hub DEGs in the WGCNA. In survival analysis of hub DEGs, high expression of PRC1 and TOP2A were significantly associated with poor clinical outcome of HBV-related HCC, and shown a good performance in HBV-related HCC diagnosis. The prognostic signature consisting of PRC1 and TOP2A also doing well in the prediction of HBV-related HCC prognosis. The diagnostic and prognostic values of PRC1 and TOP2A was confirmed in TCGA HCC patients.

Conclusions: Key biomarkers and pathways identified in the present study may enhance the comprehend of the molecular mechanisms underlying hepatocarcinogenesis. Additionally, mRNA expression of PRC1 and TOP2A may serve as potential diagnostic and prognostic biomarkers for HBV-related HCC.

• DNA topoisomerase II alpha
• hepatitis B virus
• hepatocellular carcinoma
• prognosis
• protein regulator of cytokinesis 1

• ICC
• cHCC-CC
• prognosis
• tumor number
• tumor size
• vascular invasion

Objective: The goal of our study is to identify a competing endogenous RNA (ceRNA) network using dysregulated RNAs between HCC tumors and the adjacent normal liver tissues from The Cancer Genome Atlas (TCGA) datasets, and to investigate underlying prognostic indicators in hepatocellular carcinoma (HCC) patients.

Methods: All of the RNA- and miRNA-sequencing datasets of HCC were obtained from TCGA, and dysregulated RNAs between HCC tumors and the adjacent normal liver tissues were investigated by DESeq and edgeR algorithm. Survival analysis was used to confirm underlying prognostic indicators.

Results: In the present study, we constructed a ceRNA network based on 16 differentially expressed genes (DEGs), 7 differentially expressed microRNAs and 34 differentially expressed long non-coding RNAs (DELs). Among these dysregulated RNAs, three DELs (AP002478.1, HTR2A-AS1, and ERVMER61-1) and six DEGs (enhancer of zeste homolog 2 [EZH2], kinesin family member 23 [KIF23], chromobox 2 [CBX2], centrosomal protein 55 [CEP55], cell division cycle 25A [CDC25A], and claspin [CLSPN]) were used for construct a prognostic signature for HCC overall survival (OS), and performed well in HCC OS (adjusted P<0.0001, adjusted hazard ratio = 2.761, 95% confidence interval = 1.838-4.147). Comprehensive survival analysis demonstrated that this prognostic signature may be act as an independent prognostic indicator of HCC OS. Functional assessment of these dysregulated DEGs in the ceRNA network and gene set enrichment of this prognostic signature suggest that both were enriched in the biological processes and pathways of the cell cycle, cell division and cell proliferation.

Conclusions: Our current study constructed a ceRNA network for HCC, and developed a prognostic signature that may act as an independent indicator for HCC OS.

• TCGA.
• bioinformatics
• competing endogenous RNA
• hepatocellular carcinoma
• prognosis

• combined hepatocellular-cholangiocarcinoma
• hepatocellular carcinoma
• intrahepatic cholangiocarcinoma
• prognosis
• resection

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Bile Duct Neoplasms/mortality
• Bile Duct Neoplasms/pathology
• Carcinoma, Hepatocellular/mortality
• Carcinoma, Hepatocellular/pathology
• Cholangiocarcinoma/mortality
• Cholangiocarcinoma/pathology
• Female
• Hepatitis B/epidemiology
• Humans
• Incidence
• Liver Neoplasms/mortality
• Liver Neoplasms/pathology
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Recurrence, Local
• Neoplasms, Multiple Primary/mortality
• Neoplasms, Multiple Primary/pathology
• Prognosis
• Survival Rate
• Vitamin K Deficiency/epidemiology
• Young Adult
• alpha-Fetoproteins

• Combined hepatocellular-cholangiocarcinoma
• Hepatectomy
• Liver transplantation
• Prognosis
• Treatment

• ablation
• hepatocellular carcinoma
• hepatocellular carcinoma-intrahepatic cholangiocarcinoma
• intrahepatic cholangiocarcinoma
• liver transplant
• surgery

The current study aims at using the whole genome expression profile chips for systematically investigating the diagnostic and prognostic values of excision repair cross-complementation (ERCC) genes in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Whole genome expression profile chips were obtained from the GSE14520. The receiver-operating characteristic (ROC) curve, survival analysis, and nomogram were used to investigate the diagnostic and prognostic values of ERCC genes. Investigation of the potential function of ERCC8 was carried out by gene set enrichment analysis (GSEA) and genome-wide coexpression analysis.

ROC analysis suggests that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated and may have potential to distinguish between HBV-related HCC tumor and paracancerous tissues (area under the curve of ROC ranged from 0.623 to 0.744). Survival analysis demonstrated that high ERCC8 expression was associated with a significantly decreased risk of recurrence (adjusted P=0.021; HR=0.643; 95% CI=0.442–0.937) and death (adjusted P=0.049; HR=0.631; 95% CI=0.399–0.998) in HBV-related HCC. Then, we also developed two nomograms for the HBV-related HCC individualized prognosis predictions. GSEA suggests that the high expression of ERCC8 may have involvement in the energy metabolism biological processes. As the genome-wide coexpression analysis and functional assessment of ERCC8 suggest, those coexpressed genes were significantly enriched in multiple biological processes of DNA damage and repair.

The present study indicates that six ERCC genes (ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, and ERCC8) were dysregulated between HBV-related HCC tumor and paracancerous tissues and that the mRNA expression of ERCC8 may serve as a potential biomarker for the HBV-related HCC prognosis.

• ERCC
• HBV
• diagnosis
• hepatocellular carcinoma
• prognosis

• Cisplatin
• drug therapy
• gemcitabine
• prognosis
• sorafenib

• Clear cell carcinoma
• combined hepatocellular-cholangiocarcinoma
• giant cell carcinoma
• sarcomatoid carcinoma; hepatocellular carcinoma

• TCGA
• biomarker
• hepatocellular carcinoma
• miRNA
• prognosis