• bioimaging
• biosensing
• spherical nucleic acids
• stimuli‐responsive
• therapeutics

• Biosensing Techniques/methods
• Nucleic Acids/chemistry
• Humans
• Animals

• 2022YFC2603800 National Key Research and Development Program of China
• 82122042 National Natural Science Foundation of China
• 82030066 National Natural Science Foundation of China
• 82372352 National Natural Science Foundation of China
• CSTB2022NSCQ-JQX0007 Science Fund for Distinguished Young Scholars of Chongqing Municipality

• cancer therapy
• tumour biomarkers

• Humans
• Biomarkers, Tumor/genetics
• Neoplasms/diagnosis
• Neoplasms/genetics
• Neoplasms/therapy
• Neoplasms/metabolism
• Neoplasms/drug therapy
• Precision Medicine
• Prognosis
• Molecular Targeted Therapy

• 135 Project for Disciplines of Excellence of West China Hospital Sichuan University (ZYGD23011), Natural Sciences Foundation of Sichuan (2022NSFSC0053)

• Early recurrence
• Early-stage HCC
• Microvascular invasion grade
• Nomogram

• Humans
• Carcinoma, Hepatocellular/pathology
• Nomograms
• Liver Neoplasms/pathology
• Retrospective Studies
• Hepatectomy
• Prognosis

• Hepatocellular carcinoma
• Microvascular invasion
• Nomogram
• Prediction model
• Preoperative clinical data

• Humans
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/surgery
• Carcinoma, Hepatocellular/mortality
• Liver Neoplasms/pathology
• Liver Neoplasms/surgery
• Liver Neoplasms/mortality
• Nomograms
• Female
• Male
• Middle Aged
• Retrospective Studies
• Neoplasm Invasiveness
• Hepatectomy
• Microvessels/pathology
• Risk Factors
• Aged
• Prognosis
• Predictive Value of Tests
• Risk Assessment

• Glycoside Hydrolases/chemistry
• Enzyme Inhibitors/pharmacology
• Enzyme Inhibitors/therapeutic use
• Enzyme Inhibitors/chemistry
• Glycosides
• Carbohydrates
• Glycoconjugates

• Agence Nationale de la Recherche
• Ligue Contre le Cancer
• Conseil Régional Aquitaine
• Centre National de la Recherche Scientifique

• hepatocellular carcinoma
• protein induced by vitamin K absence or antagonist-II
• recurrence
• α-fetoprotein
• γ-glutamyl transferase

• AFP-negative
• NrLR
• hepatocellular carcinoma
• inflammation
• liver resection
• prognosis

DDX20 involves the mechanism of cell proliferate, mitogenic Ets transcriptional suppressor (METS), which can arrest the cell cycle of macrophages. However, little is known about DDX20 expression, clinical values, and the relationship with tumor microenvironment in HCC.

We mined the transcriptional, protein expression and survival data of DDX20 in HCC from online databases. The immunological effects of DDX20 were estimated by bioinformatic algorithms. The RNAi and CRISPR screening were used to assess the gene effect of DDX20 for the EGFR gene in liver tumor cell.

We found that the DDX20 was highly expressed in HCC. The qRT-PCR result shows a significantly upregulated DDX20 expression in HCC samples from the West China Hospital. The high mRNA expression of DDX20 is associated with a poor survival. DDX20 expression is positively correlated with MDSCs in HCC tissues. Moreover, DDX20 has a high predicted ability for the response to immunotherapy. Furthermore, hsa-mir-324-5p could regulate the macrophage differentiation by interacting with DDX20. Meanwhile, the EGFR gene gets a high dependency score for DDX20.

In sum, DDX20 may serve as a prognostic marker for worse clinical outcomes with HCC and potentially enable more precise and personalized immunotherapeutic strategies in the future.

Glycosidases and glycosyltransferases greatly impact malignant phenotype of tumors though genetics and epigenetics mechanisms. As the member of glycoside hydrolase (GH) families 29A, α-L-fucosidases (AFUs) are involved in the hydrolysis of terminal L-fucose residues linked via α-1,2, α-1,3, α-1,4 or α-1,6 to the reducing end of N-acetyl glucosamine (GlcNAc) of oligosaccharide chains. The defucosylation process mediated by AFUs contributes to the development of various diseases, such as chronic inflammatory diseases, immune disorders, and autoimmune diseases by reducing the interaction between fucosylated adhesion molecules supporting leukocyte extravasation. AFUs also impair crucial cell-extracellular matrix (ECM) interactions and presumably subsequent cell signaling pathways, which lead to changes in tumor function and behavior. There are two isoforms of AFUs in human, namely α-L-fucosidase 1 (FUCA1) and α-L-fucosidase 2 (FUCA2), respectively. FUCA1 is a p53 target gene and can hydrolyze different fucosylation sites on epidermal growth factor receptor (EGFR), thereby determining the activation of EGFR. FUCA2 mediates the adhesion between Helicobacter pylori and gastric mucosa and is upregulated in 24 tumor types. Besides, based on the participation of AFU in signaling pathways and tumor progression, we discuss the prospect of AFU as a therapeutic target.

• Fucosidase
• cancer
• defucosylation
• microenvironment
• signaling pathway

• cancer stemness
• chemokine
• hepatocellular carcinoma
• monounsaturated fatty acid (MUFA)
• myeloid-derived suppressor cells (MDSCs)

Fucosidases are associated with several pathological conditions and play an important role in the health of the human gut. For example, fucosidases have been shown to be indicators and/or involved in hepatocellular carcinoma, breast cancer, and helicobacter pylori infections. A prerequisite for the detection and profiling of fucosidases is the formation of a specific covalent linkage between the enzyme of interest and the activity-based probe (ABP). The most commonly used fucosidase ABPs are limited to only one of the classes of fucosidases, the retaining fucosidases. New approaches are needed that allow for the detection of the second class of fucosidases, the inverting type. Here, we report an ortho-quinone methide-based probe with an azide mini-tag that selectively labels both retaining and inverting bacterial α-l-fucosidases. Mass spectrometry-based intact protein and sequence analysis of a probe-labeled bacterial fucosidase revealed almost exclusive single labeling at two specific tryptophan residues outside of the active site. Furthermore, the probe could detect and image extracellular fucosidase activity on the surface of live bacteria.

• bacteria
• fucose
• glycosidase
• probe
• proteomics
• quinone methide

Alpha-L-fucosidase-1 (FUCA1) has been demonstrated to play opposing regulatory roles in adenocarcinoma and non-adenocarcinoma. Moreover, recent studies reported that FUCA1 could decrease the invasion capability by downregulating matrix metalloproteinase 9 (MMP-9) expression. However, the potential role and prognostic significance of FUCA1 in esophageal squamous cell carcinoma (ESCC) have not yet been explored.

To evaluate the status, association, and prognostic value of FUCA1 and MMP-9 expression in ESCC.

Patients who underwent esophagectomy for ESCC between January 1, 2014, and December 31, 2014 at Sun Yat-Sen University Cancer Center were enrolled. The expression status of FUCA1 and MMP-9 in cancerous tissues was detected using immunohistochemistry. In addition, the expression profiles of the FUCA1 and MMP-9 genes in non-metastatic ESCC were extracted from The Cancer Genome Atlas (TCGA) database.

High expression of FUCA1 and MMP-9 was found in 90 patients (75.6%) and 62 patients (52.1%), respectively. In the high FUCA1 expression group, the constituent ratios of patients with stage III disease (61.1% vs 37.9%, P = 0.029), lymphatic invasion (62.2% vs 31.0%, P = 0.003), and high MMP-9 expression (60.0% vs 27.6%, P = 0.002) were significantly higher than those in the low FUCA1 expression group. In Kaplan-Meier univariate analysis, advanced tumor-node-metastasis stage (III, P = 0.001), positive regional lymph node metastasis (N+, P = 0.002), high FUCA1 expression (P = 0.001), and high MMP-9 expression (P = 0.002) were potential predictors of shorter overall survival (OS), which was similar to the results analyzed based on the TCGA database. Further Cox multivariate regression analyses still demonstrated that FUCA1 and MMP-9 expression levels were independent prognostic factors of OS [hazard ratio (HR): 0.484, 95% confidence interval (CI): 0.239-0.979; P = 0.044; and HR: 0.591, 95%CI: 0.359-0.973, P = 0.039, respectively].

FUCA1 cooperation with MMP-9 may have a major role in affecting the ESCC invasion and metastatic capability, and serve as a valuable prognostic biomarker in ESCC.

• Esophageal squamous cell carcinoma
• Alpha-L-fucosidase-1
• Matrix metalloproteinase-9
• Immunohistochemistry

• Hepatocellular carcinoma (HCC)
• overall survival (OS)
• portal vein tumor thrombus (PVTT)
• staging system

The reduced fucosylation in the spike glycoprotein of SARS-CoV-2 and the IgG antibody has been observed in COVID-19. However, the clinical relevance of α-l-fucosidase, the enzyme for defucosylation has not been discovered.

585 COVID-19 patients were included to analyze the correlations of α-l-fucosidase activity with the nucleic acid test, IgM/IgG, comorbidities, and disease progression.

Among the COVID-19 patients, 5.75% were double-negative for nucleic acid and antibodies. All of them had increased α-l-fucosidase, while only one had abnormal serum amyloid A (SAA) and C-reactive protein (CRP). The abnormal rate of α-l-fucosidase was 81.82% before the presence of IgM, 100% in the presence of IgM, and 66.2% in the presence of IgG. 73.42% of patients with glucometabolic disorders had increased α-l-fucosidase activity and had the highest mortality of 6.33%. The increased α-l-fucosidase was observed in 55.8% of non-severe cases and 72.9% of severe cases, with an odds ratio of 2.118. The α-l-fucosidase mRNA was irrelevant to its serum activity.

The change in α-l-fucosidase activity in COVID-19 preceded the IgM and SAA and showed a preferable relation with glucometabolic disorders, which may be conducive to virus invasion or invoke an immune response against SARS-CoV-2.

• Clinical relevance
• Comorbidities
• Coronavirus disease 2019 (COVID-19)
• Serological antibodies
• α-l-fucosidase

• Antibodies, Viral
• COVID-19
• Humans
• Immunoglobulin M
• SARS-CoV-2
• alpha-L-Fucosidase

Hepatocellular carcinoma (HCC) is a lethal global disease that requires an accurate diagnosis. We assessed the potential of 5 serum biomarkers (AFP, AFU, GGT-II, GPC3, and HGF) in the diagnosis of HCC.

In this retrospective study, we measured the serum levels of each biomarker using ELISAs in 921 participants, including 298 patients with HCC, 154 patients with chronic hepatitis (CH), 122 patients with liver cirrhosis (LC), and 347 healthy controls from 3 hospitals. Patients negative for hepatitis B surface antigen and hepatitis C antibody (called “NBNC-HCC”) and patients positive for the above indices (called “HBV-HCC and HCV-HCC”) were enrolled. The selected diagnostic model was constructed using a training cohort (n = 468), and a validation cohort (n = 453) was used to validate our results. Receiver operating characteristic analysis was used to evaluate the diagnostic accuracy.

The α-L-fucosidase (AFU)/α-fetoprotein (AFP) combination was best able to distinguish NBNC-HCC [area under the curve: 0.986 (95% confidence interval: 0.958–0.997), sensitivity: 92.6%, specificity: 98.9%] from healthy controls in the test cohort. For screening populations at risk of developing HCC (CH and LC), the AFP/AFU combination improved the diagnostic specificity for early-stage HCC [area under the curve: 0.776 (0.712–0.831), sensitivity: 52.5%, specificity: 91.6% in the test group]. In all-stage HBV-HCC and HCV-HCC, AFU was also the best candidate biomarker combined with AFP [area under the curve: 0.835 (0.784–0.877), sensitivity 69.1%, specificity: 87.4% in the test group]. All results were verified in the validation group.

The AFP/AFU combination could be used to identify NBNC-HCC from healthy controls and hepatitis-related HCC from at-risk patients.

• AFP
• AFU
• Hepatocellular carcinoma
• biomarker
• serum

Emerging evidence indicates that various functional genes with altered expression are involved in the tumor progression of human cancers. This study is aimed at identifying novel key genes that may be used for hepatocellular carcinoma (HCC) diagnosis, prognosis, and targeted therapy. This study included 3 expression profiles (GSE45267, GSE74656, and GSE84402), which were obtained from the Gene Expression Omnibus (GEO). GEO2R was used to analyze the differentially expressed genes (DEGs) between HCC and normal samples. The functional and pathway enrichment analysis was performed by the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network of the identified DEGs was constructed using the Search Tool for the Retrieval of Interacting Gene, and hub genes were identified. ONCOMINE and CCLE databases were used to verify the expression of the hub genes in HCC tissues and cells. Kaplan-Meier plotter was used to assess the effects of the hub genes on the overall survival of HCC patients. A total of 99 DEGs were identified from the 3 expression profiles. These DEGs were enriched with functional processes and pathways related to HCC pathogenesis. From the PPI network, 5 hub genes were identified. The expression of the 5 hub genes was all upregulated in HCC tissues and cells compared with the control tissues and cells. Kaplan-Meier survival curves indicated that high expression of cyclin-dependent kinase (CDK1), cyclin B1 (CCNB1), cyclin B2 (CCNB2), MAD2 mitotic arrest deficient-like 1 (MAD2L1), and topoisomerase IIα (TOP2A) predicted poor overall survival in HCC patients (all log-rank P < 0.01). These results revealed that the DEGs may serve as candidate key genes during HCC pathogenesis. The 5 hub genes, including CDK1, CCNB1, CCNB2, MAD2L1, and TOP2A, may serve as promising prognostic biomarkers in HCC.

• clinical trials
• genetic biomarkers
• genomic sequencing
• hepatocellular carcinoma

• Esophageal squamous cell carcinoma (ESCC)
• alpha-l-fucosidase (AFU)
• prognosis

Background: Preoperative alpha-l-fucosidase (AFU) has been used as a diagnostic biomarker for several cancers, but its role as a prognostic predictor in colorectal cancer liver oligometastasis (CLOM) patients after radical surgery has not been well defined. This study aimed to investigate the prognostic significance of preoperative serum AFU for CLOM patients after hepatic resection.

Methods: A retrospective data set was collected to evaluate the prognostic value of preoperative AFU in CLOM patients after radical hepatic resection. A total of 269 patients with histopathologically confirmed CLOM were enrolled. The optimal cut-off value of preoperative AFU was determined using X-tile software. Univariate and multivariate analyses were used to identify the prognostic significance of preoperative serum AFU.

Results: The X-tile software showed that the optimal cut-off value of preoperative AFU was set at 30.8 U/L. Patients with preoperative AFU≤30.8 and >30.8 were classified into high and low AFU groups, respectively. Female patients and those with a single liver metastasis had a higher tendency to have a preoperative AFU≤30.8 U/L; patients with lower clinical risk score (CRS) were more likely to have AFU >30.8 U/L than patients with higher CRS. The results showed that preoperative AFU was an independent prognostic factor for overall survival (OS) (P=0.041). Patients with a preoperative AFU≤30.8 U/L had a lower OS rate than those with AFU>30.8 U/L. Furthermore, for patients with lower CRS scores (0-2), the tendency clearly showed that patients with higher preoperative AFU had a better prognosis (P=0.029).

Conclusions: Higher preoperative serum AFU can predict better survival in CLOM patients after hepatic resection, especially for CLOM patients with lower CRS scores.

• CLOM
• OS
• preoperative AFU
• prognosis

α-L-fucosidases (EC 3.2.1.51, FUC), belonging to the glycoside hydrolase family 29 (GH29), play important roles in several biological processes and are markers used for detecting hepatocellular carcinoma. In this study, a protein sequence similarity network (SSN) was generated and a subsequent evolutionary analysis was performed to understand the enzymes comprehensively. The SSN indicated that the proteins in the FUC family are mainly present in bacteria, fungi, metazoans, plants, as well as in archaea, but less abundantly. The sequences in bacteria were found to be more diverse than those in other taxonomic groups. The SSN and a phylogenetic tree both supported that the proteins in the FUC family can be classified into 3 subfamilies. FUCs in each subfamily are under the pressure of negative selection. The enzymes from metazoans, fungi, and plants separated into the three subfamilies and shared high similarity with the bacterial homologs. The multiple sequence alignment results indicated that the amino acid residues for binding α-L-fucosidase and catalysis are highly conserved in the 3 subfamilies; however, the evolutionary patterns were different, based on the coevolution analysis in the subfamily of metazoans and bacteria. Finally, gene duplication plays an important role for α-L-fucosidase evolution, not only in metazoans, but also in bacteria and fungi.

• bacteria
• evolution
• metazoa
• sequence similarity network
• α-L-fucosidase

• Bee honey
• Carbon tetrachloride
• Chemotherapy
• Diethyl nitrosamine
• Hepatocellular carcinoma
• Inflammatory markers
• Oxidative stress

• Inhibitor screening
• Method validation
• UHPLC-MS
• α-L-1,3-Fucosidase

• hemolysis
• serum
• α-l-fucosidase (FUC)
• β-d-galactosidase (GAL)
• β-d-glucuronidase (GLU)

• Adult
• Female
• Glucuronidase/blood
• Hemoglobins/metabolism
• Hemolysis
• Humans
• Hydrogen-Ion Concentration
• Kinetics
• Male
• Middle Aged
• Nitrophenols/metabolism
• Young Adult
• alpha-L-Fucosidase/blood
• beta-Galactosidase/blood

Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (≥20.85 U/L) were significantly associated with favorable median OS (44.3 months versus 20.1 months; P = 0.022) in iCCA patients. Cox regression models' analyses showed that the AFU level was an independent predictor for OS (P = 0.006). Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients.

• allergy
• chemical rescue
• core fucosidase
• core α-1,3 fucosylation
• core α-1,3-fucose
• glycobiology
• glycoprotein
• mass spectrometry (MS)
• mutagenesis
• oligosaccharide

HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.

• cholangiocarcinoma
• hepatocellular carcinoma
• metastasis
• prognosis
• serum markers
• tissue markers

• Eag1
• astemizole
• diethylnitrosamine
• hepatocellular carcinoma
• ion channels

• Adult
• Aged
• Carbon Monoxide/analysis
• Carrier Proteins/genetics
• Female
• Gene Expression
• Humans
• Male
• Membrane Glycoproteins
• Membrane Proteins/genetics
• Middle Aged
• Neoplasm Proteins/genetics
• Phenotype
• Pulmonary Disease, Chronic Obstructive/etiology
• Receptors, G-Protein-Coupled/genetics
• Receptors, Peptide/genetics
• Risk Factors
• Self Report
• Smoking/adverse effects
• Smoking/blood
• Smoking/genetics
• Transcriptome
• alpha-L-Fucosidase/genetics

• CIHR

Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

• HCC
• biomarker
• liver
• lncRNA
• miRNA
• prevention
• prognosis
• therapeutic

Morphological criteria have always been considered the benchmark for selecting hepatocellular carcinoma (HCC) patients for liver transplantation (LT). These criteria, which are often inappropriate to express the tumor’s biological behavior and aggressiveness, offer only a static view of the disease burden and are frequently unable to correctly stratify the tumor recurrence risk after LT. Alpha-fetoprotein (AFP) and its progression as well as AFP-mRNA, AFP-L3%, des-γ-carboxyprothrombin, inflammatory markers and other serological tests appear to be correlated with post-transplant outcomes. Several other markers for patient selection including functional imaging studies such as ¹⁸F-FDG-PET imaging, histological evaluation of tumor grade, tissue-specific biomarkers, and molecular signatures have been outlined in the literature. HCC growth rate and response to pre-transplant therapies can further contribute to the transplant evaluation process of HCC patients. While AFP, its progression, and HCC response to pre-transplant therapy have already been used as a part of an integrated prognostic model for selecting patients, the utility of other markers in the transplant setting is still under investigation. This article intends to review the data in the literature concerning predictors that could be included in an integrated LT selection model and to evaluate the importance of biological aggressiveness in the evaluation process of these patients.

• Hepatocellular carcinoma
• Liver Alpha-fetoprotein
• Transplantation
• Biomarkers
• Histopathology
• Recurrence
• Integrated prognostic tool

• Biomarkers/blood
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/diagnostic imaging
• Carcinoma, Hepatocellular/surgery
• Fluorodeoxyglucose F18
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/diagnostic imaging
• Liver Neoplasms/surgery
• Liver Transplantation
• Patient Selection
• Positron-Emission Tomography
• Prognosis
• Protein Precursors/blood
• Prothrombin
• RNA, Messenger/blood
• RNA, Messenger/genetics
• alpha-Fetoproteins/genetics
• alpha-Fetoproteins/metabolism