scholarly journals Comprehensive Proteomic Profiling Identifies Serum Proteomic Signatures for Detection of Hepatocellular Carcinoma and Its Subtypes

2003 ◽  
Vol 49 (5) ◽  
pp. 752-760 ◽  
Author(s):  
Terence C W Poon ◽  
Tai-Tung Yip ◽  
Anthony T C Chan ◽  
Christine Yip ◽  
Victor Yip ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Confidence Interval ◽  
Control Group ◽  
Proteomic Profiling ◽  
Disease Group ◽  
Serum Samples ◽  
Flight Mass Spectrometry ◽  
Third Dimension ◽  
Artificial Network

Abstract Background: Detection of hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD) is difficult. We investigated the use of comprehensive proteomic profiling of sera to differentiate HCC from CLD. Methods: Proteomes in sera from 20 CLD patients with α-fetoprotein (AFP) <500 μg/L (control group) and 38 HCC patients (disease group) were profiled by anion-exchange fractionation (first dimension), two types (IMAC3 copper and WCX2) of ProteinChip® Arrays (second dimension), and time-of-flight mass spectrometry (third dimension). Bioinformatic tests were used to identify tumor-specific proteomic features and to estimate the values of the tumor-specific proteomic features in the diagnosis of HCC. Cross-validation was performed, and we also validated the models with pooled sera from the control and disease groups, serum from a CLD patient with AFP >500 μg/L, and postoperative sera from two HCC patients. Results: Among 2384 common serum proteomic features, 250 were significantly different between the HCC and CLD cases. Two-way hierarchical clustering differentiated HCC and CLD cases. Most HCC cases with advanced disease were clustered together and formed two subgroups that contained significantly more cases with lymph node invasion or distant metastasis. For differentiation of HCC and CLD by an artificial network (ANN), the area under the ROC curve was 0.91 (95% confidence interval, 0.82–1.01; P <0.0005) for all cases and 0.954 (95% confidence interval, 0.881–1.027; P <0.0005) for cases with nondiagnostic serum AFP (<500 μg/L). At a specificity of 90%, the sensitivity was 92%. Both cluster analysis and ANN correctly classified the pooled serum samples, the CLD serum sample with increased AFP, and the HCC patient in complete remission. Conclusion: Tumor-specific proteomic signatures may be useful for detection and classification of hepatocellular cancers.

scholarly journals Classification of Gan Dan Shi Re Pattern and Gan Shen Yin Xu Pattern in Patients with Hepatitis B Cirrhosis Using Metabonomics

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Chao-qun Zhao ◽  
Long Chen ◽  
Hong Cai ◽  
Wei-li Yao ◽  
Qun Zhou ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Metabolic Pathways ◽  
Serum Samples ◽  
Flight Mass Spectrometry ◽  
Material Basis ◽  
Data Points ◽  
Scientific Nature ◽  
Objective Basis ◽  
Important Objective

Objective. This study aimed to analyze the differential metabolites and their metabolic pathways from the serum of patients with hepatitis B cirrhosis, with two typical patterns of Gan Dan Shi Re (GDSR) and Gan Shen Yin Xu (GSYX) based on the theory of traditional Chinese medicine (TCM). It also investigated the variation in the internal material basis for the two types of patterns and provided an objective basis for classifying TCM patterns using metabolomic techniques. Methods. The serum samples taken from 111 qualified patients (40 GDSR cases, 41 GSYX cases, and 30 Latent Pattern (LP) cases with no obvious pattern characters) and 60 healthy volunteers were tested to identify the differential substances relevant to hepatitis B cirrhosis and the two typical TCM patterns under the gas chromatography–time-of-flight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis. Results. After excluding the influence of LP groups, six common substances were found in GDSR and GSYX patterns, which were mainly involved in the metabolic pathways of glycine, serine, threonine, and phenylalanine. Eight specific metabolites involved in the metabolic pathways of linoleic, glycine, threonine, and serine existed in the two patterns. Conclusions. The data points on the metabolic spectrum were found to be well distributed among the differential substances between the two typical TCM patterns of patients with hepatitis B cirrhosis using metabolomic techniques. The differential expression of these substances between GDSR and GSYX patterns provided an important objective basis for the scientific nature of TCM pattern classification at the metabolic level.

scholarly journals Is There a Role for Perioperative Nutritional Support in Liver Resection?

HPB Surgery ◽  
1997 ◽  
Vol 10 (3) ◽  
pp. 177-179
Author(s):  
Albert Bothe ◽  
Glenn Steele
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Disease ◽  
Relative Risk ◽  
Confidence Interval ◽  
Chronic Active Hepatitis ◽  
Nutritional Support ◽  
Morbidity Rate ◽  
Control Group ◽  
Percent Confidence Interval ◽  
Septic Complications

Background: Resection of hepatocellular carcinoma is associated with high rates of morbidity and mortality. Since intensive nutritional support can reduce the catabolic response and improve protein synthesis and liver regeneration, we performed a prospective study to investigate whether perioperative nutritional support could improve outcome in patients undergoing hepatectomy for hepatocellular carcinoma.Methods: We studied 124 patients undergoing resection of hepatocellular carcinoma. Sixty-four patients (39 with cirrhosis, 18 with chronic active hepatitis, and 7 with no associated liver disease) were randomly assigned to receive perioperative intravenous nutritional support in addition to their oral diet, and 60 patients (33 with cirrhosis, 12 with chronic active hepatitis, and 15 with no associated liver disease) were randomly assigned to a control group. The perioperative nutritional therapy consisted of a solution enriched with 35 percent branched chain amino acids, dextrose, and lipid emulsion (50 percent medium-chain trigylcerides) given intravenously for 14 days perioperatively).Results: There was a reduction in the overall postoperative morbidity rate in the perioperative-nutrition group as compared with the control group (34 percent vs. 55 percent; relative risk, 0.66; 95 percent confidence interval, 0.45 to 0.96), predominantly because of fewer septic complications (17 percent vs. 37 percent; relative risk, 0.57; 95 percent confidence interval, 0.34 to 0.96). There were also a reduction in the requirement for diuretic agents to control ascites (25 percent vs. 50 percent; relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87), less weight loss after hepatectomy (median loss, 0 kg vs. 1.4 kg; P=0.01), and less deterioration of liver function as measured by the change in the rate of clearance of indocyanine green (–2.8 percent vs. –4.8 percent at 20 minutes, P=0.05). These benefits were seen predominantly in the patients with underlying cirrhosis who underwent major hepatechtomy. There were five deaths during hospitalization in the perioperativenutrition group, and nine in the control group (P not significant).Conclusions: Perioperative nutritional support can reduce complications after major hepatectomy for hepatocellular carcinoma associated with cirrhosis.

scholarly journals Repeated double cross-validation applied to the PCA-LDA classification of SERS spectra: a case study with serum samples from hepatocellular carcinoma patients

2020 ◽  
Author(s):  
Elisa Gurian ◽  
Alessia Di Silvestre ◽  
Elisa Mitri ◽  
Devis Pascut ◽  
Claudio Tiribelli ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Uric Acid ◽  
Principal Components ◽  
Cross Validation ◽  
Control Group ◽  
Label Free ◽  
Serum Samples ◽  
Excitation Spectra ◽  
Linear Discriminant ◽  
Double Cross

AbstractIntense label-free surface-enhanced Raman scattering (SERS) spectra of serum samples were rapidly obtained on Ag plasmonic paper substrates upon 785 nm excitation. Spectra from the hepatocellular carcinoma (HCC) patients showed consistent differences with respect to those of the control group. In particular, uric acid was found to be relatively more abundant in patients, while hypoxanthine, ergothioneine, and glutathione were found as relatively more abundant in the control group. A repeated double cross-validation (RDCV) strategy was applied to optimize and validate principal component analysis-linear discriminant analysis (PCA-LDA) models. An analysis of the RDCV results indicated that a PCA-LDA model using up to the first four principal components has a good classification performance (average accuracy was 81%). The analysis also allowed confidence intervals to be calculated for the figures of merit, and the principal components used by the LDA to be interpreted in terms of metabolites, confirming that bands of uric acid, hypoxanthine, ergothioneine, and glutathione were indeed used by the PCA-LDA algorithm to classify the spectra.

scholarly journals Serum Prolidase Activity in Ankylosing Spondylitis and Rheumatoid Arthritis

2013 ◽  
Vol 6 ◽  
pp. CMAMD.S12602 ◽  
Author(s):  
Demet Uçar ◽  
Serda Em ◽  
Mehtap Bozkurt ◽  
Pelin Oktayoglu ◽  
Hatice Kurt Yüksel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Musculoskeletal Diseases ◽  
Control Group ◽  
Inflammatory Rheumatic Diseases ◽  
Collagen Turnover ◽  
Serum Samples ◽  
Prolidase Activity ◽  
Significant Difference

The aim of the present study was to emphasize the collagen turnover in 2 of the most common chronic inflammatory rheumatic diseases by evaluating serum prolidase activity (SPA) in ankylosing spondylitis (AS) and rheumatoid arthritis (RA). 30 patients who met the modified New York Criteria for the classification of AS, 29 patients who met the 2010 Rheumatoid Arthritis Classification Criteria for the classification of RA, and 31 healthy controls were enrolled in the study. Serum samples of the patients and the controls were collected and SPA was measured by a spectrophotometric method. The comparison of the SPA in these 3 groups was statistically examined. In both patient groups, the SPA was lower than in the control group. SPA in patients with AS was statistically significantly lower than in the control and RA groups ( P < 0.001/ P = 0.002). No statistically significant difference was found between the RA and the control groups ( P = 0.891). In conclusion, lower SPA is presumably associated with decreased collagen turnover and fibrosis, leading to decreased physical functions in both chronic inflammatory musculoskeletal diseases.

scholarly journals Serum proteomic profiling in patients with advanced Schistosoma japonicum-induced hepatic fibrosis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jing Huang ◽  
Xinguang Yin ◽  
Lifang Zhang ◽  
Ming Yao ◽  
Dahai Wei ◽  
...  
Keyword(s):  
Schistosoma Japonicum ◽  
Hepatic Fibrosis ◽  
Large Scale ◽  
Differentially Expressed ◽  
Control Group ◽  
Rapid Progression ◽  
Proteomic Profiling ◽  
Serum Samples ◽  
Data Independent Acquisition ◽  
Fundamental Information

Abstract Background Schistosoma japonicum is a parasitic flatworm that is the aetiological agent of human schistosomiasis, an important cause of hepatic fibrosis. Schistosomiasis-induced hepatic fibrosis is a consequence of the highly fibrogenic nature of egg-induced granulomatous lesions, which are the main pathogenic features of schistosomiasis. Although global awareness of the association between schistosomiasis-induced hepatic fibrosis and S. japonicum infection is increasing, little is known about the molecular differences associated with rapid progression to schistosomiasis in cirrhotic patients. Methods We systematically used data-independent acquisition (DIA)-based liquid chromatography-mass spectrometry to identify differentially expressed proteins in serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. Results Our analysis identified 1144 proteins, among which 66 were differentially expressed between the healthy control group and the group of patients with advanced S. japonicum-induced hepatic fibrosis stage F2 (SHF-F2) and 214 were differentially expressed between the SHF-F2 and SHF-F4 groups (up- or downregulation of at least 1.5-fold in serum samples). The results also indicated that two selected proteins (C1QA and CFD) are potential biomarkers for distinguishing between patients with SHF-F2 and those with SHF-F4 due to S. japonicum infection. Conclusions We provide here the first global proteomic profile of serum samples from patients with advanced S. japonicum-induced hepatic fibrosis. The proteins C1QA and CFD are potential diagnostic markers for patients with SHF-F2 and SHF-F4 due to S. japonicum infection, although further large-scale studies are needed. Our DIA-based quantitative proteomic analysis revealed molecular differences among individuals at different stages of advanced S. japonicum-induced hepatic fibrosis and may provide fundamental information for further detailed investigations. Graphic Abstract

scholarly journals Comprehensive Metabolomic Search for Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1497 ◽  
Author(s):  
Kim ◽  
Cho ◽  
Yu ◽  
Jang ◽  
Yoon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
Receiver Operating Curve ◽  
Serum Samples ◽  
Cross Sectional ◽  
Flight Mass Spectrometry ◽  
Metabolomic Profiling ◽  
Early Hcc ◽  
Disease Stages

The established biomarker for hepatocellular carcinoma (HCC), serum α-fetoprotein (AFP), has suboptimal performance in early disease stages. This study aimed to develop a metabolite panel to differentiate early-stage HCC from cirrhosis. Cross-sectional metabolomic analyses of serum samples were performed for 53 and 47 patients with early HCC and cirrhosis, respectively, and 50 matched healthy controls. Results were validated in 82 and 80 patients with early HCC and cirrhosis, respectively. To retain a broad spectrum of metabolites, technically distinct analyses (global metabolomic profiling using gas chromatography time-of-flight mass spectrometry and targeted analyses using liquid chromatography with tandem mass spectrometry) were employed. Multivariate analyses classified distinct metabolites; logistic regression was employed to construct a prediction model for HCC diagnosis. Five metabolites (methionine, proline, ornithine, pimelylcarnitine, and octanoylcarnitine) were selected in a panel. The panel distinguished HCC from cirrhosis and normal controls, with an area under the receiver operating curve (AUC) of 0.82; this was significantly better than that of AFP (AUC: 0.75). During validation, the panel demonstrated significantly better predictability (AUC: 0.94) than did AFP (AUC: 0.78). Defects in ammonia recycling, the urea cycle, and amino acid metabolism, demonstrated on enrichment pathway analysis, may reliably distinguish HCC from cirrhosis. Compared with AFP alone, the metabolite panel substantially improved early-stage HCC detection.

scholarly journals Integrated proteogenomic analysis revealed the metabolic heterogeneity in noncancerous liver tissues of patients with hepatocellular carcinoma

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Haotian Liao ◽  
Jinpeng Du ◽  
Haichuan Wang ◽  
Tian Lan ◽  
Jiajie Peng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Metabolic Reprogramming ◽  
Epigenetic Alterations ◽  
Proteomic Profiling ◽  
Free Survival ◽  
Protein Expressions ◽  
New Perspective ◽  
Metabolic Heterogeneity ◽  
Distinct Features

AbstractUnderstanding the adjacent liver microenvironment of hepatocellular carcinoma (HCC) with possible metastasis tendency might provide a strategy for risk classification of patients and potential therapies by converting the unique metastasis-inclined microenvironment to a metastasis-averse one. In this study, we performed an integrated proteogenomic analysis to have a comprehensive view on the heterogeneity of hepatic microenvironment contributing to HCC metastasis. Pairing mRNA-protein analysis revealed consistent and discordant mRNA-protein expressions in metabolism regulations and cancer-related pathways, respectively. Proteomic profiling identified three subgroups associated with the recurrence-free survival of patients. These proteomic subgroups demonstrated distinct features in metabolic reprogramming, which was potentially modified by epigenetic alterations. This study raises the point of metabolic heterogeneity in HCC noncancerous tissues and may offer a new perspective on HCC treatment.

Assessment of miR-212 and Other Biomarkers in the Diagnosis and Treatment of HBV-infection-related Liver Diseases

2019 ◽  
Vol 20 (10) ◽  
pp. 785-798 ◽  
Author(s):  
Yigan Zhang ◽  
Huaze Xi ◽  
Xin Nie ◽  
Peng Zhang ◽  
Ning Lan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Chronic Hepatitis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Liver Diseases ◽  
Meld Score ◽  
Hbv Infection ◽  
Expression Level ◽  
Control Group

Objective: Our study aims to detect the sensitivity of the new biomarker miR-212 existing in serum exosomes along with other hepatocellular carcinoma biomarkers such as AFP (alpha-fetoprotein), CA125 (carbohydrate antigen-ca125), and Hbx protein in the diagnosis of HBV-related liver diseases. We also aim to study the roles of these biomarkers in the progression of chronic hepatitis B and provide scientific data to show the clinical value of these biomarkers. Methods: We selected 200 patients with HBV-infection (58 cases of chronic hepatitis B, 47 cases of hepatocellular carcinoma, 30 cases of compensatory phase cirrhosis, and 65 cases of decompensatory phase cirrhosis), 31 patients with primary liver cancer without HBV infection, and 70 healthy individuals as the control group. The expression level of serum AFP and CA125 was detected with electrochemiluminescence immunoassay. The expression level of the Hbx protein was detected with ELISA. Meanwhile, the expression level of miR-212 in serum was analyzed with RT-qPCR. We collected patients’ clinical information following the Child-Pugh classification and MELD score criterion, and statistical analysis was made between the expression level of miR-212 and the collected clinical indexes. Lastly, we predicted the target genes of the miR-212 and its functions using bioinformatics methods such as cluster analysis and survival prediction. Results: Compared to the control group, the expression level of miR-212 in HBV infected patients was remarkably increased (P<0.05), especially between the HBV-infection Hepatocellular carcinoma group and the non-HBVinfection liver cancer group (P<0.05). The expression of miR-212 was increased in patients’ Child-Pugh classification, MELD score, and TNM staging. Moreover, the sensitivity and specificity of miR-212 were superior to AFP, CA125, and HBx protein. Conclusion: There is a linear relationship between disease progression and expression level of miR-212 in the serum of HBV infected patients. This demonstrates that miR-212 plays a significant role in liver diseases. miR-212 is expected to be a new biomarker used for the diagnosis and assessment of patients with HBV-infection-related liver diseases.

scholarly journals Radiofrequency ablation versus repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma in subcapsular location: a retrospective cohort study

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fuqun Wei ◽  
Qizhen Huang ◽  
Yang Zhou ◽  
Liuping Luo ◽  
Yongyi Zeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Repeat Hepatectomy ◽  
Free Survival ◽  
Recurrent Hepatocellular Carcinoma ◽  
Primary Endpoints ◽  
Grade 3 ◽  
Optimal Treatment Strategy ◽  
Hepatectomy Group

Abstract Background Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial. Methods A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3. Results There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group. Conclusion Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.

scholarly journals Retinal vascular fractal dimensions and their association with macrovascular cardiac disease.

2021 ◽  
Author(s):  
Sebastian Dinesen ◽  
Pia Søndergaard Jensen ◽  
Maria Bloksgaard ◽  
Søren Leer Blindbæk ◽  
Jo G.R. De Mey ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Cardiac Disease ◽  
Artery Bypass ◽  
Fractal Dimensions ◽  
Macrovascular Disease ◽  
Control Group ◽  
Vascular Structure ◽  
Non Invasive ◽  
Automatic Software ◽  
Multivariable Regression

Introduction As the only part of the human vasculature, retina is available for direct, non-invasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher non-integer values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases and this study examined the association of DF and macrovascular cardiac disease in a case-control design. Methods Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semi-automatic software VAMPIRE was used to measure retinal DF. Results Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p=0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval, 1.63 to 31.86; p=0.009) and second quartile (OR, 8.25; 95% confidence interval, 1.70 to 40.01; p=0.009). Conclusions This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess non-ocular macrovascular disease.

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