scholarly journals Autoantibody to GNAS in Early Detection of Hepatocellular Carcinoma: A Large-Scale Sample Study Combined with Verification in Serial Sera from HCC Patients

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 97
Author(s):  
Xiao Wang ◽  
Keyan Wang ◽  
Cuipeng Qiu ◽  
Bofei Wang ◽  
Xiaojun Zhang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Detection ◽  
Large Scale ◽  
Early Stage ◽  
Decompensated Cirrhosis ◽  
Compensated Cirrhosis ◽  
Autoantibody Response ◽  
Potential Biomarker ◽  
Early Hcc ◽  
Normal Controls

The aim of this study was to explore the value of autoantibody to GNAS in the early detection of hepatocellular carcinoma (HCC). In a large-scale sample set of 912 participants (228 cases in each of HCC, liver cirrhosis (LC), chronic hepatitis B (CHB), and normal controls (NCs) groups), autoantibody to GNAS was detected with a positive result in 47.8% of HCC patients, which was significantly higher than that in patients with LC (35.1%), CHB (19.7%), and NCs (19.7%). Further analysis showed that the frequency of autoantibody to GNAS started increasing in compensated cirrhosis patients (37.0%) with a jump in decompensated cirrhosis patients (53.2%) and reached a peak in early HCC patients (62.4%). The increasing autoantibody response to GNAS in patients at different stages was closely associated with the progression of chronic liver lesions. The result from 44 human serial sera demonstrated that 5 of 11 (45.5%) HCC patients had elevated autoantibody to GNAS before and/or at diagnosis of HCC. Moreover, 46.1% and 62.4% of high positive rates in alpha-fetoprotein (AFP) negative and early-stage HCC patients can supplement AFP in early detection of HCC. These findings suggest that autoantibody to GNAS could be used as a potential biomarker for the early detection of HCC.

scholarly journals PRM-MS Quantitative Analysis of Isomeric N-Glycopeptides Derived From Human Serum Haptoglobin of Patients With Cirrhosis and Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Cristian D. Gutierrez Reyes ◽  
Yifan Huang ◽  
Mojgan Atashi ◽  
Jie Zhang ◽  
Jianhui Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Detection ◽  
Large Scale ◽  
Scale Validation ◽  
Area Under The Curve ◽  
Glycosylation Site ◽  
Protein Glycosylation ◽  
Serum Haptoglobin ◽  
Parallel Reaction Monitoring ◽  
Early Hcc

Abstract Currently surveillance strategies have inadequate performance for the early detection of hepatocellular carcinoma (HCC). Protein glycosylation is a potential source of biomarkers to differentiate between cirrhosis and HCC. We performed a comprehensive LC-PRM-MS approach where a targeted parallel reaction monitoring (PRM) strategy was coupled to a powerful LC system to study the microheterogeneity of haptoglobin (Hp) extracted from 15 patients with cirrhosis and 15 with HCC. We found that our strategy was able to identify a large number of isomeric N-glycopeptides mainly located in the glycosylation site Asn207. Nine out of twelve N-glycopeptides, located in the Asn207 site, had significant differences in abundance between patients with cirrhosis and HCC (p < 0.05). The area under the curve (AUC) of alpha-fetoprotein (AFP) was alone 0.85, which improved to 0.95 (95% CI: 0.88, 1) when NLF_5613 Isomer 1 was combined with AFP. When comparing the early HCC vs. cirrhosis, four sialylated-fucosylated glycopeptides better estimated AUCs with respect to AFP (AUCAFP = 0.66, and AUCN−glycopeptides = 0.86, 0.84, 0.88, and 0.80, respectively). Further large scale validation of glycopeptides for the early detection of HCC is warranted.

scholarly journals Autoantibody Response to Murine Double Minute 2 Protein in Immunodiagnosis of Hepatocellular Carcinoma

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Mei Liu ◽  
Su-jun Zheng ◽  
Yu Chen ◽  
Ning Li ◽  
Peng-fei Ren ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Stage ◽  
High Titer ◽  
Immunofluorescence Assay ◽  
Tissue Array ◽  
Enzyme Linked Immunosorbent Assay ◽  
Autoantibody Response ◽  
Potential Biomarker ◽  
Human Sera ◽  
And Control

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide. Although new therapeutic strategies have been continuously developed and applied to clinical treatment for HCC, the prognosis is still very poor. Thus, early detection of HCC may enhance effective and curative management. In this study, autoantibody responses to MDM2 protein in HCC patient’s serum were evaluated by enzyme-linked immunosorbent assay (ELISA) and part sera were evaluated by Western blotting and indirect immunofluorescence assay. Immunohistochemistry (IHC) over tissue array slides was also performed to analyze protein expression of MDM2 in HCC and control tissues. The prevalence of autoantibodies against MDM2 was significantly higher than that in liver cirrhosis (LC), chronic hepatitis (CH), and normal human sera (NHS). The average titer of autoantibodies against MDM2 in HCC serum was higher compared to that in LC, CH, and NHS. A high titer of autoantibodies against MDM2 in ELISA could be observed in the serum in 6 to 9 months before the clinical diagnosis of HCC in the serum of several HCC patients with serial bleeding samples. Our preliminary data indicate that MDM2 and anti-MDM2 system may be a potential biomarker for early stage HCC screening and immunodiagnosis.

scholarly journals Discovery and validation of novel protein markers in mucosa of portal hypertensive gastropathy

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ying Zhu ◽  
Wen Xu ◽  
Wei Hu ◽  
Fang Wang ◽  
Yan Zhou ◽  
...  
Keyword(s):  
Portal Hypertension ◽  
Gastric Mucosa ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Trial Registration ◽  
Portal Hypertensive Gastropathy ◽  
Protein Markers ◽  
Decompensated Liver Cirrhosis ◽  
Potential Biomarker ◽  
Normal Controls

Abstract Background Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. Methods We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein. Results LFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment. Trial registration and ethics approval: Trial registration was completed (ChiCTR2000029840) on February 25, 2020. Ethics Approvals were completed on July 17, 2017 (NYSZYYEC20180003) and February 15, 2020 (NYSZYYEC20200005).

scholarly journals Serum CYR61 As A Potential Biomarker for The Diagnosis of Esophagogastric Junction Tumor

2021 ◽  
Author(s):  
Ling-Yu Chu ◽  
Jian-Yuan Zhou ◽  
Yi-Xuan Zhao ◽  
Yan-Ting Ou ◽  
Tian Yang ◽  
...  
Keyword(s):  
Early Stage ◽  
Area Under The Curve ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Operating Characteristics ◽  
Tumor Patients ◽  
Chi Square ◽  
Potential Biomarker ◽  
The Difference ◽  
Normal Controls

Background：Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P&lt;0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P&gt;0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

scholarly journals Quantitative proteomics identifies a plasma multi-protein model for detection of hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhenhua Du ◽  
Xinyi Liu ◽  
Xiaojun Wei ◽  
Hongbo Luo ◽  
Peiyao Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Membrane Proteins ◽  
Early Detection ◽  
Proteomic Analysis ◽  
Quantitative Proteomics ◽  
Serum Biomarkers ◽  
Diagnostic Efficacy ◽  
Protein Model ◽  
Tumor Tissues ◽  
Normal Controls

Abstract More efficient biomarkers are needed to facilitate the early detection of hepatocellular carcinoma (HCC). We aimed to identify candidate biomarkers for HCC detection by proteomic analysis. First, we performed a global proteomic analysis of 10 paired HCC and non-tumor tissues. Then, we validated the top-ranked proteins by targeted proteomic analyses in another tissue cohort. At last, we used enzyme-linked immunosorbent assays to validate the candidate biomarkers in multiple serum cohorts including HCC cases (HCCs), cirrhosis cases (LCs), and normal controls (NCs). We identified and validated 33 up-regulated proteins in HCC tissues. Among them, eight secretory or membrane proteins were further evaluated in serum, revealing that aldo–keto reductase family 1 member B10 (AKR1B10) and cathepsin A (CTSA) can distinguish HCCs from LCs and NCs. The area under the curves (AUCs) were 0.891 and 0.894 for AKR1B10 and CTSA, respectively, greater than that of alpha-fetoprotein (AFP; 0.831). Notably, combining the three proteins reached an AUC of 0.969, which outperformed AFP alone (P < 0.05). Furthermore, the serum AKR1B10 levels dramatically decreased after surgery. AKR1B10 and CTSA are potential serum biomarkers for HCC detection. The combination of AKR1B10, CTSA, and AFP may improve the HCC diagnostic efficacy.

scholarly journals A Large‐scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma

Hepatology ◽  
2018 ◽  
Vol 67 (2) ◽  
pp. 662-675 ◽  
Author(s):  
Ping Luo ◽  
Peiyuan Yin ◽  
Rui Hua ◽  
Yexiong Tan ◽  
Zaifang Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Early Detection ◽  
Large Scale ◽  
Biomarker Identification

A multicenter nonrandomized controlled trial to evaluate the efficacy of surgery versus radiofrequency ablation for small hepatocellular carcinoma (SURF cohort trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4581-4581
Author(s):  
Ryosuke Tateishi ◽  
Kiyoshi Hasegawa ◽  
Yoshikuni Kawaguchi ◽  
Tadatoshi Takayama ◽  
Namiki Izumi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Early Stage ◽  
Controlled Trial ◽  
Patient Characteristics ◽  
Small Hepatocellular Carcinoma ◽  
Multicenter Randomized Controlled Trial ◽  
Early Hcc ◽  
The Difference

4581 Background: In parallel with a multicenter randomized controlled trial that reported an equal recurrence-free survival (RFS) of early-stage hepatocellular carcinoma (HCC) patients who underwent either surgery (SUR) or radiofrequency ablation (RFA), we also enrolled HCC patients who fulfilled the enrollment criteria but did not give consent to participate in the RCT. Methods: All patients gave informed consent to participate in this study. Inclusion criteria were as follows: primary HCC with less than or equal to 3 tumors, each measuring 3 cm or smaller; without vascular invasion or extrahepatic metastasis; Child-Pugh score of 7 or less; and ages between 20 and 79 years. The feasibility for both treatments was confirmed by a joint chart review by surgeons and hepatologists. The primary endpoint was RFS and overall survival. A pre-specified interim analysis was performed to compare RFS. Results: Between April 2009 and August 2015, 740 patients (371 in SUR, 369 in RFA) were enrolled from 49 participating hospitals in Japan. The SUR group had significantly fewer patients with chronic hepatitis C (56.6% vs. 69.4%), higher median value of platelet count (145 vs. 120 × 109/L), and more patients with > 2 cm tumors (49.9% vs. 27.9%); most patients had a single tumor (91.1% vs. 88.3%). During the median follow-up period of 5 years, tumor recurrence was observed in 192 of SUR and 218 of RFA with 3-year RFS being 66.0% and 61.7%, respectively ( P = 0.091). In subgroup analysis, RFS was significantly better in SUR in patients with ≤ 2 cm tumors (62.9% vs. 51.7% in 3 years; hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.56-0.93; P = 0.014), whereas the difference was not significant in those with > 2 cm tumors (52.7% vs. 46.4%; HR 0.85, 95% CI 0.63-1.18; P = 0.34). The adjusted HR for RFS using inversed probability of treatment weighting was 0.89 (95% CI, 0.72-1.10; P = 0.287). Conclusions: The imbalance in patient characteristics reflected a real-world practice. Factors related to background liver disease rather than tumor characteristics might have a larger impact on the recurrence in early HCC. Clinical trial information: C000001796 .

scholarly journals Health State Utilities and Quality of Life in Patients with Hepatitis B

2012 ◽  
Vol 26 (7) ◽  
pp. 445-451 ◽  
Author(s):  
Gloria Woo ◽  
George Tomlinson ◽  
Colina Yim ◽  
Les Lilly ◽  
George Therapondos ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Hepatocellular Carcinoma ◽  
Standard Gamble ◽  
Antiviral Treatment ◽  
Decompensated Cirrhosis ◽  
Health State ◽  
Disease States ◽  
Compensated Cirrhosis ◽  
Health State Utilities

BACKGROUND: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized.OBJECTIVE: To measure utility scores and HRQoL across disease states associated with CHB infection.METHODS: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities.RESULTS: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores.CONCLUSIONS: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.

scholarly journals The frequency of occurrence of Hepatocellular Carcinoma after direct antiviral therapy in Hepatitis C virus patients

2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Bilal Aziz ◽  
Tazeen Nazar ◽  
Suhair Akhlaq
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Antiviral Therapy ◽  
Sampling Technique ◽  
Decompensated Cirrhosis ◽  
Frequency Of Occurrence ◽  
Genotype 3 ◽  
Cross Sectional ◽  
Compensated Cirrhosis

Objective: To study the frequency of occurrence of hepatocellular carcinoma (HCC) in hepatitis C virus patients treated with direct acting antiviral (DAA) agents. Methods: This hospital based cross-sectional study was conducted in Mayo Hospital, Lahore from June, 2016 to January, 2018. Total 300 patients with HCV genotype 3, selected via Non-Probability Purposive Sampling technique, without prior or concurrent history of HCC, were given DAA agents and were followed up for 6 months after completion of therapy. Results were based on Quantitative PCR to assess Sustained Virological Response (SVR) and Ultrasound Abdomen to look for the appearance of any new lesion. Data was presented as mean±SD, frequency and percentages and was analyzed using SPSS Version 24.0. Results: Out of 300 patients, 179 (59.7%) were males and 121(40.3%) were females. Mean age of the patients was 55.08 ± 5.602 years. 214(71.3%) patients had compensated cirrhosis at the start of treatment and 86(28.7%) had decompensated cirrhosis. SVR was achieved in 200(93.4%) out of 214 patients with compensated cirrhosis and in 76(88.3%) out of 86 patients with decompensated cirrhosis. At six months post- treatment, 10(3.33%) patients developed HCC,2(0.7%) in the compensated group and 8(2.7%) in the decompensated group, out of which 5(6.6%) patients had achieved SVR. Conclusion: The frequency of HCC following DAA agents is significant (3.3%) even after achieving SVR. Caution must be exercised in prescribing DAA agents to HCV patients keeping this complication of HCC in mind. How to cite this:Aziz B, Nazar T, Akhlaq S. The frequency of occurrence of Hepatocellular Carcinoma after direct antiviral therapy in Hepatitis C virus patients. Pak J Med Sci. 2019;35(1):---------. doi: https://doi.org/10.12669/pjms.35.1.109 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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