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Liu X, Lu Y, Zhou W, Peng T, Zhou J, Bi H, Xia F, Chen X. Chinese Multidisciplinary Expert Consensus on Immune Checkpoint Inhibitor-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition). Liver Cancer 2024; 13:355-375. [PMID: 39114757 PMCID: PMC11305662 DOI: 10.1159/000535496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Accepted: 11/10/2023] [Indexed: 08/10/2024] Open
Abstract
Background Immune checkpoint inhibitor (ICI)-based combination therapy modalities for hepatocellular carcinoma (HCC) have achieved significant efficacy in clinical research and practice and have become the mainstay for the treatment of unresectable HCC. Summary To better help clinicians use combination immunotherapy drugs and regimens rationally, effectively, and safely, the editorial board facilitated a discussion with multidisciplinary experts in the field, adopted the "Delphi" consensus formation method, and finally revised and completed the "Chinese Multidisciplinary Expert Consensus on the Immune Checkpoint Inhibitors (ICIs)-Based Combination Therapy for Hepatocellular Carcinoma (2023 Edition)" on the basis of the 2021 edition. Key Messages This consensus primarily focuses on the principles and methods of clinical practice of combination therapy based on ICIs, aiming to summarize the recommendations for clinical application based on the latest research and expert experience and provide application guidance for clinicians.
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Affiliation(s)
- Xiufeng Liu
- Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China
| | - Yinying Lu
- Comprehensive Liver Cancer Center, 5th Medical Center of PLA General Hospital, Beijing, China
| | - Weiping Zhou
- Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Tao Peng
- Hepatobiliary Surgery Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Jie Zhou
- Division of Hepatobiliopancreatic Surgery and Liver Transplantation, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Huaqiang Bi
- Department of Hepatobiliary Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Feng Xia
- Department of Hepatobiliary Surgery, The First Hospital Affiliated to Army Medical University, Chongqing, China
| | - Xiaoping Chen
- Department of Hepatobiliary Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
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Huang C, Xiao X, Tong L, Gao Z, Ji J, Zhou L, Li Y, Liu L, Feng H, Fang M, Gao C. Risks and Clinical Predictors of Hepatocellular Carcinoma in Chinese Populations: A Real-World Study of 10,359 Patients in Six Medical Centers. J Hepatocell Carcinoma 2024; 11:411-425. [PMID: 38435681 PMCID: PMC10908286 DOI: 10.2147/jhc.s447700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 02/07/2024] [Indexed: 03/05/2024] Open
Abstract
Purpose Early detection of hepatocellular carcinoma (HCC) through surveillance could reduce this cancer-associated mortality. We aimed to develop and validate algorithms using panel serum biomarkers to identify HCC in a real-world multi-center study in China. Patients and Methods A total of 10,359 eligible subjects, including HCCs and benign liver diseases (BLDs), were recruited from six Chinese medical centers. The three nomograms were built using logistic regression and their sensitivities and specificities were carefully assessed in training and validation cohorts. HCC patients after surgical resection were followed to determine the prognostic values of these algorithms. Prospective surveillance performance was assessed in a cohort of chronic hepatitis B patients during 144 weeks follow-up. Results Independent risk factors such as alpha-fetoprotein (AFP), lens cuinaris agglutinin-reactive fraction of AFP (AFP-L3), des-gamma-carboxy prothrombin (DCP), albumin (ALB), and total bilirubin (TBIL) obtained from train cohort were used to construct three nomograms (LAD, C-GALAD, and TAGALAD) using logistic regression. In the training and two validation cohorts, their AUCs were all over 0.900, and the higher AUCs appeared in TAGALAD and C-GALAD. Furthermore, the three nomograms could effectively stratify HCC into two groups with different survival and recurrence outcomes in follow-up validation. Notably, TAGALAD could predict HCC up to 48 weeks (AUC: 0.984) and 24 weeks (AUC: 0.900) before clinical diagnosis. Conclusion The proposed nomograms generated from real-world Chinese populations are effective and easy-to use for HCC surveillance, diagnosis, as well as prognostic evaluation in various clinical scenarios based on data feasibility.
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Affiliation(s)
- Chenjun Huang
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China
| | - Xiao Xiao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China
| | - Lin Tong
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Zhiyuan Gao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China
| | - Jun Ji
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Lin Zhou
- Department of Laboratory Medicine, Shanghai Changzheng Hospital, Shanghai, 200003, People’s Republic of China
| | - Ya Li
- Department of Laboratory Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China
| | - Lijuan Liu
- Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
| | - Huijuan Feng
- Department of Laboratory Medicine, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, People’s Republic of China
| | - Meng Fang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
| | - Chunfang Gao
- Department of Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, People’s Republic of China
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, 200438, People’s Republic of China
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Orabi MAA, Abouelela ME, Darwish FMM, Abdelkader MSA, Elsadek BEM, Al Awadh AA, Alshahrani MM, Alhasaniah AH, Aldabaan N, Abdelhamid RA. Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules. Front Pharmacol 2024; 15:1337910. [PMID: 38370475 PMCID: PMC10871037 DOI: 10.3389/fphar.2024.1337910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Accepted: 01/19/2024] [Indexed: 02/20/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.
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Affiliation(s)
- Mohamed A. A. Orabi
- Department of Pharmacognosy, College of Pharmacy, Najran University, Najran, Saudi Arabia
| | - Mohamed E. Abouelela
- Department of Pharmacognosy, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt
| | - Faten M. M. Darwish
- Department of Pharmacognosy, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | | | - Bakheet E. M. Elsadek
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
| | - Ahmed Abdullah Al Awadh
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia
| | - Mohammed Merae Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia
| | - Abdulaziz Hassan Alhasaniah
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Najran University, Najran, Saudi Arabia
| | - Nayef Aldabaan
- Department of Pharmacology, College of Pharmacy, Najran University, Najran, Saudi Arabia
| | - Reda A. Abdelhamid
- Department of Pharmacognosy, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt
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Yu WM, Li GW, Lou MG, Wu ZY. A meta-analysis of the prognostic impact of tissue golgi protein 73 (tGP73) in hepatocellular carcinoma. BMC Gastroenterol 2023; 23:401. [PMID: 37978447 PMCID: PMC10656938 DOI: 10.1186/s12876-023-03050-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 11/09/2023] [Indexed: 11/19/2023] Open
Abstract
INTRODUCTION To date, an increasing number of studies have revealed that GP73 may have prognostic value in liver cancer. However, most of the studies evaluated serum GP73, and the results regarding the prognostic value of tGP73 in liver cancer are still controversial. Therefore, in this meta-analysis, we aimed to determine whether tGP73 has any prognostic value in patients with HCC. MATERIALS AND METHODS Relevant publications were searched for in PubMed, EMBASE, OVID, the Cochrane Library, and the Web of Science databases up to March 2023. The hazard ratio (HR) or odds ratio (OR) with corresponding 95% confidence intervals (95% CIs) of eligible studies were assessed by fixed-effects or random-effects models. In addition, subgroup analyses were conducted to investigate the possible causes of heterogeneity, and publication bias analysis was also performed to assess the reliability of the meta-analysis results. RESULTS A total of 10 studies were included. These studies included 1569 HCC patients, and a meta-analysis was performed. The results of our meta-analysis showed that higher GP73 expression levels were significantly associated with poorer OS (HR = 1.87, 95% CI: 1.41-2.48, P < 0.0001, I2 = 58%). However, there was no significant correlation between high GP73 expression and disease-free survival (DFS) (HR: 1.43, 95% CI: 0.93-2.33, P = 0.100). In addition, abnormal GP73 expression was also related to higher tumour tissue differentiation grade (OR = 3.03, 95% CI = 2.01-4.57, P < 0.0001, I2 = 89%), later tumour stage (OR = 5.89, 95% CI = 2.31-14.99, P < 0.0001, I2 = 0%), vascular invasion (OR = 1.72, 95% CI = 1.12-2.64, P = 0.010, I2 = 0%), multiple tumours (OR = 2.44, 95% CI = 1.37-3.68, P = 0.001, I2 = 44%) and early postoperative tumour recurrence (OR = 1.92, 95% CI = 1.10-3.28, P = 0.020, I2 = 62%). CONCLUSIONS The meta-analysis showed that the overexpression of GP73 may be related to a poor prognosis of HCC, and it may also have a predictive effect on the invasion and metastasis of HCC.
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Affiliation(s)
- Wei-Ming Yu
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China.
| | - Guo-Wei Li
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Ming-Geng Lou
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
| | - Zheng-Yu Wu
- Department of Hepatobiliary and pancreatic surgery, The First People's Hospital of Fuyang District, Fuyang First Hospital Affiliated to Binjiang College of Zhejiang Chinese Medicine University, Hangzhou, China
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Haque S, Bhushan Raman R, Salam M. Role of Biomarkers in Hepatocellular Carcinoma and Their Disease Progression. LIVER CANCER - GENESIS, PROGRESSION AND METASTASIS 2023. [DOI: 10.5772/intechopen.105856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the third leading and common lethal cancers worldwide. Early detection of tumorigenesis of hepatocellular carcinoma is through ultrasonography, computerized tomography (CT) scans, and magnetic resonance imaging (MRI) scans; however, these methods are not up to the mark, so a search for an efficient biomarker for early diagnosis and treatment of hepatocarcinogenesis is important. Proteomic and genomic approaches aid to develop new promising biomarkers for the diagnosis of HCC at the early stages. These biomarkers not only help in prognosis but also provide better therapeutic intervention against HCC. Among the different biomarker candidates, liquid biopsy [including circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)] has recently emerged as a noninvasive detection technique for the characterization of circulating cells, providing a strong basis and early diagnosis for the individualized treatment of patients. This review provides the current understanding of HCC biomarkers that predict the risk of HCC recurrence.
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Sun LY, Ouyang Q, Cen WJ, Wang F, Tang WT, Shao JY. A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy. Am Surg 2023; 89:1468-1478. [PMID: 34894786 DOI: 10.1177/00031348211063549] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. METHODS A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. RESULTS In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. CONCLUSIONS The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.
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Affiliation(s)
- Li-Yue Sun
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Qing Ouyang
- Department of Hepatobiliary, General Hospital of Southern Theatre Command of PLA, Guangzhou, China
| | - Wen-Jian Cen
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Fang Wang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Wen-Ting Tang
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jian-Yong Shao
- State Key Laboratory of Oncology in South China, Guangzhou, China
- Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
- Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, China
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Zhang H, Xu M, Shao J, Kong H, Gao X, Zhang W, Chang X, Yang B, Chen Y, Dong Z, Huang J, Zeng Z, Yang Y. Age independent survival benefit for patients with small hepatocellular carcinoma undergoing percutaneous cryoablation: A propensity scores matching study. Front Oncol 2023; 13:1072054. [PMID: 36741016 PMCID: PMC9895933 DOI: 10.3389/fonc.2023.1072054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Accepted: 01/02/2023] [Indexed: 01/22/2023] Open
Abstract
Background Hepatocellular carcinoma (HCC) is the major cause of malignancy-related deaths worldwide, and its incidence is likely to increase in the future as life expectancy increases. Therefore, the management of elderly patients with HCC has become a global issue. Aim of this study was to assess whether elderly patients with small HCC could obtain survival benefit from cryoablation (CRYO) in a real-world. Materials and methods From July 2007 to June 2013, 185 patients with small HCC who underwent curative-intent percutaneous CRYO. All patients were divided into three groups according to age distribution. Overall survival (OS) and tumor-free survival (TFS) were compared between among of groups before and after the 1:1 propensity score matching, respectively. Univariate and multivariate Cox analyses were performed to determine the potential relationships between variables and prognostic outcomes. Results One hundred and eighty-five patients (144 men, 41 women) received CRYO for small HCC, including 59 patients with age <50 years, 105 patients with age between 50 and 65 years, and 21 patients with age >65 years. The three age groups showed significant differences in the terms of underlying chronic liver disease and the number of patients with minor postoperative complications. After propensity score matching, the younger and elderly groups showed significant differences in mean OS (P=0.008) and tumor progression (P=0.050). However, no significant differences were shown in mean progression-free survival (PFS) (P=0.303). The Cox multivariate analysis showed that the Child-Pugh grade (HR=3.1, P<0.001), albumin (HR=0.85, P=0.004) and total of bilirubin (HR=1, P=0.024) were the independent prognostic factor for mean OS. Conclusion Our propensity-score-matched study suggested that elderly patients with small HCC can achieve acceptable prognostic outcomes with PFS similar to those of younger patients with small HCC after treatment with CRYO, while Child-Pugh grade, bilirubin and serum albumin levels were associated with the prognosis of small HCCs.
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Affiliation(s)
- Huixin Zhang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Muoyan Xu
- Healthcare Office of Chinese PLA General Hospital, Beijing, China
| | - Jiashen Shao
- Department of Orthopedics, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Huifang Kong
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xudong Gao
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Wei Zhang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Xiujuan Chang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Bin Yang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Yan Chen
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zheng Dong
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Jiagan Huang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Zhen Zeng
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China,*Correspondence: Yongping Yang, ; Zhen Zeng,
| | - Yongping Yang
- Department of Liver Diseases, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China,*Correspondence: Yongping Yang, ; Zhen Zeng,
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Liu A, Li Y, Shen L, Shen L, Li Z. Clinical utility of serum fucosylated fraction of alpha-fetoprotein in the diagnostic of hepatocellular carcinoma: a comprehensive analysis with large sample size. Aging (Albany NY) 2022; 14:2645-2664. [PMID: 35307694 PMCID: PMC9004564 DOI: 10.18632/aging.203963] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 03/15/2022] [Indexed: 05/13/2023]
Abstract
We conducted a comprehensive meta-analysis of the utility of AFP-L3 for the diagnosis of hepatocellular carcinoma, to provide a more accurate estimation for the clinical utility of AFP-L3. We performed online searches in five databases (PubMed, China National Knowledge Infrastructure, Wanfang, Web of Science, and Embase), from inception to December 31, 2021. Pooled sensitivity, specificity, and area under the curve (AUC) with the matching 95% confidence intervals (95% CIs) were calculated to estimate the diagnostic value of AFP-L3. Thirty-four studies were included in the meta-analysis. The pooled sensitivity was 0.70 [95% confidence interval (CI): 0.63-0.77], and the specificity was 0.91 (95% CI: 0.88-0.94). The estimated area under the curve (AUC) was 0.90 (95% CI: 0.87-0.92). The positive likelihood ratio and negative likelihood ratio were 7.78 (95% CI: 5.7-10.7) and 0.33 (95% CI: 0.26-0.41), respectively. The diagnostic odds ratio was 24 (95% CI: 16-37). The subgroup analysis indicated moderate sensitivity (0.79) and high specificity (0.89) for the Asian population (AUC = 0.89), and similar specificity (0.95) but lower sensitivity (0.35) for Caucasians (AUC = 0.80). Deeks' funnel plot asymmetry test detected no publication bias (P = 0.460). The sensitivity analysis showed that the pooled results were stable. Taken together, our results indicated that AFP-L3 demonstrates high diagnostic ability for HCC, especially among Asian populations. AFP-L3 is a useful means for high-volume screening, which can help doctors optimize diagnosis workflow, reduce workload, and improve detection sensitivity. The combination of multiple biomarkers may provide more accurate diagnostic tools for HCC in the future.
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Affiliation(s)
- Aibin Liu
- Department of Geriatrics, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
| | - Yanyan Li
- Department of Nursing, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
| | - Lin Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
| | - Zhanzhan Li
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province 410008, PR China
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Li B, Liu A, Wen Y, Yang G, Zhao J, Li X, Mao Y, Li B. The prognostic values of serum markers in hepatocellular carcinoma after invasive therapies based on real-world data. J Clin Lab Anal 2021; 35:e23932. [PMID: 34403527 PMCID: PMC8418514 DOI: 10.1002/jcla.23932] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Revised: 06/29/2021] [Accepted: 07/22/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) is one of the most common malignancy with poor prognosis, and the mortality rate remains high. More than 70% of HCC patients have recurrence within 5 years after treatment. The purpose of this study is to evaluate the prognostic values of serum markers with retrospective data. METHODS We applied real-world data (RWD) to analyze the prognostic values of six serum markers for HCC patients after treatment, including α-fetoprotein (AFP), α-fetoprotein-L3 (AFP-L3), Golgi protein73 (GP73), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin (TBil). A total of 268 cases were enrolled to analyze recurrence-free survival (RFS), and 104 cases were used to analyze overall survival (OS). RESULTS Our results demonstrated that patients with higher AFP and AFP-L3 had shorter RFS (p = 0.016 and 0.004), while higher GP73, ALT, and TBil experienced longer RFS (p = 0.000, 0.020, and 0.019). Patients with high-level GP73, ALT, TBil, and low-level ALB had significantly higher mortality rate (p=0.035, 0.008, 0.010, and 0.005). Multivariate analysis revealed that GP73 (HR = 1.548, p = 0.001) and ALT (HR = 1.316, p = 0.046) were identified as independent prognostic factors for RFS, ALB (HR = 0.127, p = 0.007), and ALT (HR = 0.237, p = 0.01) were identified as independent prognostic factors for OS. Subgroups analysis showed that GP73 had better prognostic values than other serum markers in early-stage HCC (p = 0.023). CONCLUSIONS Our study demonstrates that AFP, AFP-L3, and GP73 can be used as prognostic indicators for predicting the recurrence of HCC, while liver function tests have better survival prediction values. GP73 can act as a promising prognostic marker for early-stage HCC.
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Affiliation(s)
- Bo Li
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Aixia Liu
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Yi Wen
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Guang Yang
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Jing Zhao
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Xiaohan Li
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Yuanli Mao
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Boan Li
- Department of Clinical LaboratoryThe Fifth Medical Center of Chinese PLA General HospitalBeijingChina
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Gatselis NK, Tornai T, Shums Z, Zachou K, Saitis A, Gabeta S, Albesa R, Norman GL, Papp M, Dalekos GN. Golgi protein-73: A biomarker for assessing cirrhosis and prognosis of liver disease patients. World J Gastroenterol 2020; 26:5130-5145. [PMID: 32982114 PMCID: PMC7495033 DOI: 10.3748/wjg.v26.i34.5130] [Citation(s) in RCA: 41] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 05/19/2020] [Accepted: 08/20/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Reliable biomarkers of cirrhosis, hepatocellular carcinoma (HCC), or progression of chronic liver diseases are missing. In this context, Golgi protein-73 (GP73) also called Golgi phosphoprotein-2, was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells. As a result, GP73 expression was found primarily in biliary epithelial cells, with only slight detection in hepatocytes. However, in patients with acute or chronic liver diseases and especially in HCC, the expression of GP73 is significantly up-regulated in hepatocytes. So far, few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression. AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression. METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA (QUANTA Lite® GP73, Inova Diagnostics, Inc., Research Use Only) in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa, Greece (n = 366) and Debrecen, Hungary (n = 266). Aspartate aminotransferase (AST)/Platelets (PLT) ratio index (APRI) was also calculated at the relevant time points in all patients. Two hundred and three patients had chronic hepatitis B, 183 chronic hepatitis C, 198 alcoholic liver disease, 28 autoimmune cholestatic liver diseases, 15 autoimmune hepatitis, and 5 with other liver-related disorders. The duration of follow-up was 50 (57) mo [median (interquartile range)]. The development of cirrhosis, liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines. In particular, the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein (AFP) determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients. RESULTS Increased serum levels of GP73 (> 20 units) were detected at initial evaluation in 277 out of 632 patients (43.8%). GP73-seropositivity correlated at baseline with the presence of cirrhosis (96.4% vs 51.5%, P < 0.001), decompensation of cirrhosis (60.3% vs 35.5%, P < 0.001), presence of HCC (18.4% vs 7.9%, P < 0.001) and advanced HCC stage (52.9% vs 14.8%, P = 0.002). GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score [Area under the curve (AUC) (95%CI): 0.909 (0.885-0.934) vs 0.849 (0.813-0.886), P = 0.003]. Combination of GP73 with APRI improved further the accuracy (AUC: 0.925) compared to GP73 (AUC: 0.909, P = 0.005) or APRI alone (AUC: 0.849, P < 0.001). GP73 levels were significantly higher in HCC patients compared to non-HCC [22.5 (29.2) vs 16 (20.3) units, P < 0.001) and positively associated with BCLC stage [stage 0: 13.9 (10.8); stage A: 17.1 (16.8); stage B: 19.6 (22.3); stage C: 32.2 (30.8); stage D: 45.3 (86.6) units, P < 0.001] and tumor dimensions [very early: 13.9 (10.8); intermediate: 19.6 (18.4); advanced: 29.1 (33.6) units, P = 0.004]. However, the discriminative ability for HCC diagnosis was relatively low [AUC (95%CI): 0.623 (0.570-0.675)]. Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline, was prognostic of higher rates of decompensation (P = 0.036), HCC development (P = 0.08), and liver-related deaths (P < 0.001) during follow-up. CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination. In combination with APRI, its diagnostic performance can be further improved. Most importantly, the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and non-viral chronic liver diseases.
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Affiliation(s)
- Nikolaos K Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
- Institute of Internal Medicine and Hepatology, Larissa 41447, Greece
| | - Tamás Tornai
- Department of Internal Medicine, Division of Gastroenterology, University of Debrecen, Faculty of Medicine, Debrecen H-4032, Hungary
| | - Zakera Shums
- Department of Research and Development, Inova Diagnostics, Inc., San Diego, CA 92131, United States
| | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
- Institute of Internal Medicine and Hepatology, Larissa 41447, Greece
| | - Asterios Saitis
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
| | - Stella Gabeta
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
| | - Roger Albesa
- Department of Research and Development, Inova Diagnostics, Inc., San Diego, CA 92131, United States
| | - Gary L Norman
- Department of Research and Development, Inova Diagnostics, Inc., San Diego, CA 92131, United States
| | - Mária Papp
- Department of Internal Medicine, Division of Gastroenterology, University of Debrecen, Faculty of Medicine, Debrecen H-4032, Hungary
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, National Expertise Center of Greece in Autoimmune Liver Diseases, General University Hospital of Larissa, Larissa 41110, Greece
- Institute of Internal Medicine and Hepatology, Larissa 41447, Greece
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Wang T, Zhang KH. New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma. Front Oncol 2020; 10:1316. [PMID: 32923383 PMCID: PMC7456927 DOI: 10.3389/fonc.2020.01316] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 06/24/2020] [Indexed: 12/18/2022] Open
Abstract
An early diagnosis of hepatocellular carcinoma (HCC) followed by effective treatment is currently critical for improving the prognosis and reducing the associated economic burden. Alpha-fetoprotein (AFP) is the most widely used biomarker for HCC diagnosis. Based on elevated serum AFP levels as well as typical imaging features, AFP-positive HCC (APHC) can be easily diagnosed, but AFP-negative HCC (ANHC) is not easily detected due to lack of ideal biomarkers and thus mainly reliance on imaging. Imaging for the diagnosis of ANHC is probably insufficient in sensitivity and/or specificity because most ANHC tumors are small and early-stage HCC, and it is involved in sophisticated techniques and high costs. Moreover, ANHC accounts for nearly half of HCC and exhibits a better prognosis compared with APHC. Therefore, the diagnosis of ANHC in clinical practice has been a critical issue for the early treatment and prognosis improvement of HCC. In recent years, tremendous efforts have been made to discover new biomarkers complementary to AFP for HCC diagnosis. In this review, we systematically review and discuss the recent advances of blood biomarkers for HCC diagnosis, including DNA biomarkers, RNA biomarkers, protein biomarkers, and conventional laboratory metrics, focusing on their diagnostic evaluation alone and in combination, in particular on their diagnostic performance for ANHC.
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Affiliation(s)
- Ting Wang
- Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Kun-He Zhang
- Department of Gastroenterology, Jiangxi Institute of Gastroenterology & Hepatology, The First Affiliated Hospital of Nanchang University, Nanchang, China
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12
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α-Fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) in prognosis of hepatocellular carcinoma after radiofrequency. EGYPTIAN LIVER JOURNAL 2019. [DOI: 10.1186/s43066-019-0008-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Numerous hepatocellular carcinoma (HCC) biomarkers have been assessed in the diagnosis and prognosis of HCC. The aim of this study was to assess the value of α-fetoprotein (AFP)-L3% and transforming growth factor B1 (TGFB1) as prognostic markers in hepatocellular carcinoma after radiofrequency ablation (RFA). This observational cohort study included 40 patients with HCC diagnosed by triphasic computed tomography criteria indicated for radiofrequency ablation. Serum AFP, AFP-L3%, and TGFB1 were measured in all patients before and 3 months after radiofrequency ablation.
Results
Statistically significant lower levels of TGFB1, AFP, and AFP-L3% were noted in the HCC patients after radiofrequency ablation. Significant lower levels of TGFB1, AFP, and AFP-L3% were found in the no recurrence group in comparison to the recurrence group. The cutoff value of TGFB1 > 56.87 ng/mL, AFP > 74.9 ng/mL, and AFP-L3% > 8.5% was the best in the discrimination of tumor recurrence with sensitivity of 85.7%, 57.1%, and 100%; specificity of 54.6%, 84.9%, and 100%; and diagnostic accuracy of 64.5%, 69%, and 100%, respectively.
Conclusion
TGFB1 and AFP-L3% are good prognostic markers for HCC. They could be used to monitor the response of HCC to treatment.
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Elsayed MMA, Mostafa ME, Alaaeldin E, Sarhan HAA, Shaykoon MS, Allam S, Ahmed ARH, Elsadek BEM. Design And Characterisation Of Novel Sorafenib-Loaded Carbon Nanotubes With Distinct Tumour-Suppressive Activity In Hepatocellular Carcinoma. Int J Nanomedicine 2019; 14:8445-8467. [PMID: 31754301 PMCID: PMC6825507 DOI: 10.2147/ijn.s223920] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2019] [Accepted: 10/05/2019] [Indexed: 12/18/2022] Open
Abstract
PURPOSE Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar®), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula. MATERIALS AND METHODS Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model). RESULTS The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers. CONCLUSION Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.
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Affiliation(s)
- Mahmoud MA Elsayed
- Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Sohag University, Sohag, Egypt
| | - Mahmoud E Mostafa
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Eman Alaaeldin
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt
- Department of Clinical Pharmacy, Deraya University, Minia, Egypt
| | - Hatem AA Sarhan
- Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt
| | - Montaser ShA Shaykoon
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
| | - Shady Allam
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh, Egypt
| | - Ahmed RH Ahmed
- Department of Pathology, Faculty of Medicine, Sohag University, Sohag, Egypt
| | - Bakheet EM Elsadek
- Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
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Esawy MM, Shabana MA, Ahmed NH. Effect of sample type and storage conditions on Golgi membrane protein 73 stability. Scandinavian Journal of Clinical and Laboratory Investigation 2019; 79:491-495. [PMID: 31495236 DOI: 10.1080/00365513.2019.1661009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
GP73 is a transmembrane glycoprotein that increases in viral and non-viral liver diseases, especially in hepatocellular carcinoma. This study aims to evaluate the effect of sample type and storage conditions on GP73 concentration. Twenty subjects were enrolled in this study. Serum and citrated plasma samples were collected. Both were subjected to different time intervals and storage temperature. Baseline GP73 concentrations ranged from 1.7 to 16.9 ng/mL in serum samples, and from 1.1 to 15.3 ng/mL in citrated plasma (Mann-Whitney U test, p = .1). The acceptable change limit for GP73 was 6.1%. As the highest value of the median percentage deviation was -5.3% in both sample types at different storage condition so, deviations were within the accepted limits. But there were considerable variations in the GP-73 concentrations after 2 cycles of freezing and thawing at -20 °C. This study shows that both serum and citrated plasma can be used for the measurement of GP73 concentration. GP73 seems to be stable under common storage conditions, but it may be unstable with frequent cycles of freezing and thawing.
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Affiliation(s)
- Marwa M Esawy
- Department of Clinical Pathology, Faculty of Human Medicine, Zagazig University , Zagazig , Egypt
| | - Marwa A Shabana
- Department of Clinical Pathology, Faculty of Human Medicine, Zagazig University , Zagazig , Egypt
| | - Nabila H Ahmed
- Department of Tropical Medicine, Faculty of Human Medicine, Zagazig University , Zagazig , Egypt
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15
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Li N, Zhao L, Guo C, Liu C, Liu Y. Identification of a novel DNA repair-related prognostic signature predicting survival of patients with hepatocellular carcinoma. Cancer Manag Res 2019; 11:7473-7484. [PMID: 31496805 PMCID: PMC6689532 DOI: 10.2147/cmar.s204864] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Accepted: 07/19/2019] [Indexed: 12/14/2022] Open
Abstract
Purpose Hepatocellular carcinoma (HCC) is the sixth most lethal neoplasm worldwide. Traditional biomarkers often exploit the relationship between a certain gene and cancer progression, but they cannot predict patient survival or prognosis accurately. We aim to construct a new DNA repair-related gene signature that combines several genes to improve prognosis prediction in HCC. Methods We selected an HCC mRNA sequencing (mRNA-seq) dataset (n=365) from The Cancer Genome Atlas (TCGA), and gene set enrichment analysis (GSEA) was used to explore bioinformatics information and further screen genes. We then built a gene signature based on the Cox proportional hazards regression model. Results GSEA revealed that the hallmark DNA repair gene set was significantly upregulated in the tumor phenotype. A set of seven genes, namely, ADA, FEN1, POLR2G, SAC3D1, SEC61A1, SF3A3, and UPF3B, were significantly a
ssociated with overall survival (OS) and used to form a gene signature. The signature risk score was calculated and used to divide patients into high‐ and low‐risk groups. The high-risk group showed worse prognosis (log-rank test p<0.0001). Univariate and multivariate Cox regression analysis showed that the prognostic performance of this risk score signature was robust in different subgroups based on clinicopathological features, with p-values <0.05 (HR=2.38, 95% CI (confidence interval) =1.355–4.184), indicating that it can serve as an independent prognostic indicator. Conclusion We developed and identified a seven‐gene signature related to the DNA repair process that can predict survival in HCC. It can be used as an effective classification tool and to guide clinical treatment.
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Affiliation(s)
- Na Li
- Department of Central Laboratory, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People's Republic of China
| | - Lan Zhao
- Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, Liaoning, People's Republic of China
| | - Chunyan Guo
- Department of Pharmacy, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People's Republic of China
| | - Chang Liu
- Department of Thoracic Surgery, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People's Republic of China
| | - Yongyu Liu
- Department of Thoracic Surgery, Shenyang Tenth People's Hospital, Shenyang Chest Hospital, Shenyang, Liaoning, People's Republic of China
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16
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Shalably NM, Badawi R, Hawash N, Abd-Elsalam S, Elkhalawany W, Hameed AAEI, Alkassas GED. Evaluation of Fucosylated Haptoglobin as a Diagnostic Biomarker for Hepatocellular Carcinoma in Egypt. THE OPEN BIOMARKERS JOURNAL 2019; 9:31-37. [DOI: 10.2174/1875318301909010031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2019] [Revised: 05/31/2019] [Accepted: 06/11/2019] [Indexed: 12/25/2022]
Abstract
Background:
Most Hepatocellular Carcinomas (HCCs) are diagnosed at an advanced stage. Therefore, there is citation-type an urgent need for better methods of detection and surveillance of patients at risk of HCC. Alpha-fetoprotein (AFP) has a suboptimal diagnostic performance for HCC surveillance, so novel and reliable diagnostic biomarkers are required.
Objective:
The aim of this work is to evaluate fucosylated haptoglobin as a diagnostic biomarker for hepatocellular carcinoma in Egyptian patients.
Materials and Methods:
This case-control study was carried out on 60 patients classified into 3 groups (20 patients on each); group I (HCC group), group II (Cirrhotic group) and group III (Control group). Diagnosis of liver cirrhosis was done by clinical, biochemical and ultrasound (US), whereas the diagnosis of HCC was done by percutaneous biopsy or radiological (by US and triphasic Computerized Tomography (CT) based on the guidelines of the American-Association for the Study of Liver Diseases. HCC stage was clinically defined according to the Barcelona Clinic Liver Cancer (BCLC) staging system. AFP & fucosylated haptoglobin levels were estimated in all groups.
Results:
There was a statistically significant positive correlation between serum fucosylated haptoglobin and tumor size in the HCC group. Serum fucosylated haptoglobin (at 116 U/ ml) showed sensitivity 80%, specificity 65%, positive predictive value 53% and negative predictive value 87% with AUC 0.786. Combination of serum fucosylated haptoglobin and serum AFP at (200 ng/ ml) increased sensitivity that reached 95%.
Conclusion:
Serum fucosylated haptoglobin may serve as a novel diagnostic biomarker for the detection of HCC with higher sensitivity than AFP.
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Chen J, Chen J, Gong Y, Zou B, Liu X, Ding L, Huang J, Zhang B, Li J. C14orf166 Is a Biomarker for Predicting Hepatocellular Carcinoma Recurrence. J INVEST SURG 2019; 33:914-923. [PMID: 30907217 DOI: 10.1080/08941939.2019.1586015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Jianxu Chen
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jiandi Chen
- Department of Endocrinology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Yihang Gong
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Baojia Zou
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Xialei Liu
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Lei Ding
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jiaxing Huang
- Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, China
| | - Baimeng Zhang
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Jian Li
- Department of Hepatobiliary Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
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18
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Xia Y, Zhang Y, Shen M, Xu H, Li Z, He N. Golgi protein 73 and its diagnostic value in liver diseases. Cell Prolif 2019; 52:e12538. [PMID: 30341783 PMCID: PMC6496820 DOI: 10.1111/cpr.12538] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 08/29/2018] [Accepted: 09/04/2018] [Indexed: 02/06/2023] Open
Abstract
Golgi protein 73 (GP73, also referred to as Golph 2) with 400 amino acids is a 73 kDa transmembrane glycoprotein typically found in the cis-Golg complex. It is primarily expressed in epithelial cells, which has been found upregulated in hepatocytes in patients suffering from both viral and non-viral liver diseases. GP73 has drawn increasing attention for its potential application in the diagnosis of liver diseases such as hepatitis, liver cirrhosis and liver cancer. Herein, we reviewed the discovery history of GP73 and summarized studies by many groups around the world, aiming at understanding its structure, expression, function, detection methods and the relationship between GP73 and liver diseases in various settings.
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Affiliation(s)
- Yanyan Xia
- Department of Clinical LaboratoryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
| | - Yuanying Zhang
- Department of Molecular BiologyJiangsu Cancer HospitalNanjingChina
| | - Mengjiao Shen
- Department of Clinical LaboratoryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
| | - Hongpan Xu
- Department of Clinical LaboratoryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
| | - Zhiyang Li
- Center of Laboratory MedicineThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
| | - Nongyue He
- State Key Laboratory of BioelectronicsSoutheast UniversityNanjingChina
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Chen PF, Li QH, Zeng LR, Yang XY, Peng PL, He JH, Fan B. A 4-gene prognostic signature predicting survival in hepatocellular carcinoma. J Cell Biochem 2018; 120:9117-9124. [PMID: 30582205 DOI: 10.1002/jcb.28187] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 11/12/2018] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To develop an independent prognostic signature for patients with hepatocellular carcinoma (HCC). METHODS HCC gene expression profile the cancer genome atlas-liver hepatocellular carcinoma and GSE14520 were used as discovery and test set, respectively. Differentially expressed genes (DEGs) were identified between HCC tissues and adjacent normal liver tissues. Univariate Cox proportional hazards regression analysis was performed to identify DEGs correlated with survival of HCC patients. A 4-gene-based signature was constructed based on a least absolute shrinkage and selection operator Cox penalized regression model. The predictive value of the signature was analyzed and validated. RESULTS Two hundred sixty-three DEGs were identified between HCC and adjacent liver tissues. After univariate survival analysis, 90 DEGs were found to be significantly correlated with the overall survival (OS) of HCC patients, of which 4 genes (KPNA2, CDC20, SPP1, and TOP2A) with non-zero coefficient were used to construct a prognostic signature. The 4-gene signature was significantly associated with the age (P = 0.046), grade ( P = 0.022), and T stage ( P = 0.023) of HCC patients in the discovery set and it also significantly associated with TNM stage ( P = 0.033), and serum alpha-fetoprotein lever ( P = 0.034). Patients in the 4-gene low-risk group were associated with better OS and recurrence-free survival (RFS) than those in the high-risk group in the discovery and test set. Meanwhile, the 4-gene signature is an independent prognostic factor regarding OS and RFS in the discovery and test set. CONCLUSION We developed a 4-gene-based signature, which could be a candidate prognostic factor for patients with HCC.
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Affiliation(s)
- Peng-Fei Chen
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Qing-He Li
- Department of Hepatobiliary Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Li-Rong Zeng
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Xue-Ying Yang
- Department of Medical Records, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Pai-Lan Peng
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Jian-Hua He
- Department of Gastroenterology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
| | - Bin Fan
- Department of Hepatobiliary Surgery, The Central Hospital of Enshi Autonomous Prefecture, Enshi, China
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Canale M, Ulivi P, Foschi FG, Scarpi E, De Matteis S, Donati G, Ercolani G, Scartozzi M, Faloppi L, Passardi A, Tamburini E, Valgiusti M, Marisi G, Frassineti GL, Casadei Gardini A. Clinical and circulating biomarkers of survival and recurrence after radiofrequency ablation in patients with hepatocellular carcinoma. Crit Rev Oncol Hematol 2018; 129:44-53. [PMID: 30097237 DOI: 10.1016/j.critrevonc.2018.06.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Revised: 06/08/2018] [Accepted: 06/19/2018] [Indexed: 02/08/2023] Open
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21
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Chau I, Park JO, Ryoo BY, Yen CJ, Poon R, Pastorelli D, Blanc JF, Kudo M, Pfiffer T, Hatano E, Chung HC, Kopeckova K, Phelip JM, Brandi G, Ohkawa S, Li CP, Okusaka T, Hsu Y, Abada PB, Zhu AX. Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study. Br J Cancer 2018; 119:19-26. [PMID: 29808014 PMCID: PMC6035236 DOI: 10.1038/s41416-018-0103-0] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 04/04/2018] [Accepted: 04/11/2018] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. METHODS Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. RESULTS Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). CONCLUSIONS Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.
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Affiliation(s)
- Ian Chau
- Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, SM2 5PT, UK.
| | - Joon Oh Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 135-710, Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea
| | - Chia-Jui Yen
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, 701, Taiwan
| | - Ronnie Poon
- Departmentof Surgery, The University of Hong Kong, Pokfulam, Hong Kong
| | - Davide Pastorelli
- Department of Oncology, Santa Maria del Prato Hospital, Feltre (Belluno), 32032, Italy
| | - Jean-Frédéric Blanc
- Department of Hepato-Gastroenterology and Medical Oncology, CHU de Bordeaux, Hôpital Haut-Lévêque, 33604, Pessac, France
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka-Sayama, 589-8511, Japan
| | - Tulio Pfiffer
- Department of Medical Oncology, Instituto do Câncer do Estado de São Paulo, São Paulo, 01246-000, Brazil
| | - Etsuro Hatano
- Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, 606-8507, Japan
| | - Hyun Cheol Chung
- Department of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 03722, Korea
| | - Katerina Kopeckova
- Department of Oncology, University Hospital Motol, 2nd Faculty of Medicine of Charles University, 150 00, Praha, Czech Republic
| | - Jean-Marc Phelip
- Department of Gastroenterology and Digestive Oncology, University Hospital of St Etienne, 42100, Saint Etienne, France
| | - Giovanni Brandi
- Department of Experimental, Diagnostic and Specialty Medicine, University Hospital S. Orsola, 40138, Bologna, Italy
| | - Shinichi Ohkawa
- Division of Hepatobiliary and Pancreatic Oncology, Kanagawa Cancer Center, Yokohama, 241-0815, Japan
| | - Chung-Pin Li
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, 112, Taiwan
- National Yang-Ming University School of Medicine, Taipei, 112, Taiwan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, 104-0045, Japan
| | - Yanzhi Hsu
- Eli Lilly and Company, New York, NY, 10016, USA
| | | | - Andrew X Zhu
- Department of Medicine, Harvard Medical School, Massachusetts General Hospital, Boston, MA, 02114, USA
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王 媛, 周 陈, 李 静, 周 玲, 李 明, 肖 冰. [Value of detection of serum glypican-3 level in diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma]. NAN FANG YI KE DA XUE XUE BAO = JOURNAL OF SOUTHERN MEDICAL UNIVERSITY 2017; 37:1060-1065. [PMID: 28801286 PMCID: PMC6765739 DOI: 10.3969/j.issn.1673-4254.2017.08.10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/14/2017] [Indexed: 06/07/2023]
Abstract
OBJECTIVE To explore the clinical value of detecting serum glypican-3 in the diagnosis and therapeutic effect evaluation of primary hepatocellular carcinoma (PHC). METHODS Using sandwich ELISA, we detected serum glypican-3 levels in 60 patients with PHC, 60 with metastatic liver cancer, 50 with liver cirrhosis, 50 with chronic viral hepatitis, 20 with hepatic cyst, 20 with fatty liver, 20 with hepatic hemangioma and 20 with drug-induced hepatitis as well as in 40 healthy subjects (control). We also analyzed the changes in serum levels of glypican-3 and alpha fetoprotein (AFP) in PHC patients after treatment. RESULTS PHC patients had significantly higher serum levels of glypican-3 than patients with other liver diseases and the control subjects (P<0.05). The levels of serum glypican-3 were significantly higher in patients with metastatic liver cancer, liver cirrhosis and viral hepatitis than in those with other benign liver diseases and the control subjects (P<0.05). Glypican-3 level was not associated with AFP level or liver function in PHC patients, in whom the positivity rates for glypican-3 and AFP were 65% and 56.7%, respectively. The detection rate of PHC increased to 85% by a combined detection of AFP and glypican-3. In the 23 PHC patients who responded positively to treatments, serum glypican-3 level showed a steady decline compared with that in 15 patients before treatment, while serum AFP level showed a similar decrease only in 10 patients. CONCLUSION Combined detection of glypican-3 and AFP is expected to improve the early diagnosis rate of PHC. The different thresholds of serum glypican-3 may play a role in the differential diagnosis of PHC and other various liver diseases. Glypican-3 may serve as a better marker than AFP with a high specificity and sensitivity for evaluating the therapeutic effect in PHC patients.
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Affiliation(s)
- 媛媛 王
- 南方医科大学南方医院, 肿瘤内科, 广东 广州 510515Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515
- 南方医科大学南方医院, 消化内科, 广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 陈杰 周
- 南方医科大学珠江医院肝胆外科, 广东 广州 510280Department of Hepatobiliary Surgery, Zhujiang Hospital Southern Medical University, Guangzhou 510280, China
| | - 静 李
- 南方医科大学南方医院, 消化内科, 广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 玲 周
- 南方医科大学南方医院, 肿瘤内科, 广东 广州 510515Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515
| | - 明松 李
- 南方医科大学南方医院, 消化内科, 广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
| | - 冰 肖
- 南方医科大学南方医院, 消化内科, 广东 广州 510515Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
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Xiao W, Zhao S, Shen F, Liang J, Chen J. Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma. Exp Ther Med 2017; 14:2637-2642. [PMID: 28962206 DOI: 10.3892/etm.2017.4818] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 05/05/2017] [Indexed: 12/21/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The aim of the present study was to reveal the prognostic significance of CD147 and to preliminarily explore the molecular mechanisms involved. Blood and tumor tissue specimens were obtained from 133 HCC patients. All patients were followed up for 4 years. The serum and tissue levels of CD147 were analyzed using ELISA and immunohistochemistry, respectively. The SMMC-7721 hepatoma carcinoma cell line was transfected with CD147 overexpression vector and cell migration was evaluated using a wound healing assay. Extracellular signal-regulated kinase (ERK) inhibitor UO126 was applied to study the role of the ERK pathway in cell migration. CD147 expression in HCC tissue was associated with poor prognosis of patients [odds ratio (OR): 3.13, 95% confidence interval (CI): 1.52-6.43], and patients with no CD147 expression had a significantly survival advantage (P=0.016). However, serum CD147 levels had no such prognostic significance (OR: 1.94, 95% CI: 0.96-3.91; P=0.097). In the wound healing assay, the wound distance in the non-transfected cell group was wider than that in the transfected cell group without UO126 treatment (178.0±31.1 vs. 106.0±20.7 µm; P=0.003), but similar to that in the transfected cell group with 10 µM UO126 treatment (170.4±13.2 µm; P=0.629). The present study revealed that the expression of CD147 in HCC tissue is an independent prognostic indicator. In addition CD147 overexpression may be associated with tumor cell migration and ERK signaling pathway activation.
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Affiliation(s)
- Wenjing Xiao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Shufen Zhao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Fangzhen Shen
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Jun Liang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Jing Chen
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
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The antitumor activity of a lactosaminated albumin conjugate of doxorubicin in a chemically induced hepatocellular carcinoma rat model compared to sorafenib. Dig Liver Dis 2017; 49:213-222. [PMID: 27825923 DOI: 10.1016/j.dld.2016.10.003] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 09/22/2016] [Accepted: 10/03/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND Worldwide, consistent survival benefit for chemotherapy in hepatocellular carcinoma (HCC) is a golden goal for concerned researchers. Nexavar® (sorafenib) is the only approved agent that achieved touchable successes in this regard. Thus, there is a pressing medical need for new promising drugs to improve HCC therapy. AIMS our designed lactosaminated albumin conjugate of doxorubicin (L-HSA-DOXO) that rapidly and preferentially accumulates in the liver is compared, for the first time at its MTD, with doxorubicin and sorafenib, not only for antitumor efficacy but also for overall survival. METHODS HCC was induced in male Wistar rats with N-nitrosodiethylamine added to drinking water (100mg/L) for 8 weeks. Endpoints were antitumor efficacy, tolerability and overall survival. RESULTS L-HSA-DOXO proved to be superior at least over doxorubicin in the majority of assessed endpoints. Circulating AFP-L3% was diminished in L-HSA-DOXO (14.5%) and sorafenib (18.4%) groups compared to DENA (31.1%) and doxorubicin (29.5%) groups. This superiority was further confirmed by Western blot analyses of some novel HCC biomarkers. Survival study reinforced consistent benefits of both L-HSA-DOXO and sorafenib. CONCLUSIONS L-HSA-DOXO shows at least comparable activity to sorafenib which clinically achieves only ∼3 months overall survival benefit. Combination of these two agents could act beneficially or synergistically via two different modes of action to fight HCC.
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25
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A sensitive three monoclonal antibodies based automatic latex particle-enhanced turbidimetric immunoassay for Golgi protein 73 detection. Sci Rep 2017; 7:40090. [PMID: 28054632 PMCID: PMC5215377 DOI: 10.1038/srep40090] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Accepted: 12/01/2016] [Indexed: 12/17/2022] Open
Abstract
Golgi protein 73 (GP73) is a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) that has been found to be abnormally elevated in liver disease. A latex particle-enhanced turbidimetric immunoassay (LTIA) was recently introduced and licensed for application in a variety of automated clinical chemistry analyzers. However, no studies have reported sufficient data on analytical performance of this method when using 3 monoclonal antibodies for GP73 measurement. The experimental conditions were firstly optimized and range of linearity, diagnostic potential, clinical relevance were compared with the LTIA based on polyclonal antibodies and ELISA. Dilution tests for the LTIA using 3 monoclonal antibodies produced a calibration curve from 10 to 350 ng/mL while the polyclonal antibodies produced the curve from 20 to 320 ng/mL. The detection limit was achieved at 1.82 ng/mL concentration. Within-run CV was obtained in the range of 1.5-2.9% and ROC curves indicated sensitivity and specificity of the LTIA based on 3 monoclonal antibodies were 96.7% and 93.3%, respectively, higher than for the polyclonal antibodies (94.6% and 72.4%) and ELISA (70.0% and 83.3%). Therefore, the LTIA assay based on 3 monoclonal antibodies is thus applicable in quantification of GP73 concentration in automated biochemistry analyzers.
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26
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Abouzied MM, Eltahir HM, Fawzy MA, Abdel-Hamid NM, Gerges AS, El-Ibiari HM, Nazmy MH. Estimation of leucine aminopeptidase and 5-nucleotidase increases alpha-fetoprotein sensitivity in human hepatocellular carcinoma cases. Asian Pac J Cancer Prev 2015; 16:959-63. [PMID: 25735389 DOI: 10.7314/apjcp.2015.16.3.959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To find parameters that can increase alpha-fetoprotein (AFP) sensitivity and so help in accurate diagnosis and rapid management of hepatocullular carcinoma (HCC), as AFP has limited utility of distinguishing HCC from benign hepatic disorders for its high false-positive and false negative rates. MATERIALS AND METHODS Serum levels of AFP, 5'-nucleotidase enzyme activity (5-NU) and leucine aminopeptidase enzyme (LAP) activity were measured in 40 individuals. RESULTS LAP and 5'NU were elevated in HCC at p<0.001. Pearson correlation coefficients showed that changes in AFP exhibited positive correlation with both 5'-NU and LAP at (p<0.001). The complementary use of LAP only with AFP resulted in an increase in sensitivity of AFP from 75% to 90% in detecting HCC. The complementary use of both LAP and 5-NU with AFP resulted in an increased sensitivity of AFP in detecting HCC from 75% to 95%. CONCLUSIONS LAP and 5-FU can be determined in HCC patients in combination with AFP to improve its sensitivity and decrease false negative results.
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Affiliation(s)
- Mekky Mohammed Abouzied
- Departments of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Kingdom of Saudi Arabia E-mail :
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Li QW, Chen HB, Li ZY, Shen P, Qu LL, Gong LL, Xu HP, Pang L, Si J. Preparation and characterization of anti-GP73 monoclonal antibodies and development of double-antibody sandwich ELISA. Asian Pac J Cancer Prev 2015; 16:2043-9. [PMID: 25773808 DOI: 10.7314/apjcp.2015.16.5.2043] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Serum Golgi protein 73 (GP73) as a novel and potential marker for diagnosing hepatocellular carcinoma (HCC) have been found to be elevated in HCC patients and associated with clinical variables representing tumor growth and invasiveness. The aim of this study was to prepare a pair of monoclonal antibodys (mAbs) against GP73 and develop a newly designed double-antibody sandwich enzyme-linked immunosorbent assay (s-ELISA), which would be used in the detection of serum GP73 (sGP73) as well as in the diagnosis of HCC. MATERIALS AND METHODS Produced by prokaryotic expression, the purified recombinant GP73 (rGP73), produced by prokaryotic expression, was used to immunize the Balb/c mice. Two hybridoma cell lines against GP73 were obtained by fusing mouse Sp2/0 myeloma cells with spleen cells from the immunized mice. The titers of anti-GP73 mAb reached 1:243,000. Western blotting analysis and Immunohistochemistry staining revealed that anti-GP73 mAb could recognize GP73 protein. The double-antibody s-ELISA was successfully established and validated by 119 HCC and 103 normal serum samples. RESULTS showed that the detection limit of this method could reach 1.56 ng/ml, and sGP73 levels in HCC group (mean=190.6 ng/ml) were much higher than those of in healthy controls (mean=70.92 ng/ml). CONCLUSIONS Results of our study not only showed that sGP73 levels of HCC patients were significantly higher than those of healthy controls, but also indicated that the laboratory homemade anti-GP73 mAbs could be the optimal tool used in evaluating sGP73 levels, which would provide a solid foundation for subsequent clinical applications.
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Affiliation(s)
- Qi-Wen Li
- Department of Laboratory Medicine, The Second Affiliated Hospital, Nanjing Medical University, Nanjing, China E-mail :
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Sai W, Wang L, Zheng W, Yang J, Pan L, Cai Y, Qiu L, Zhang H, Wu W, Yao D. Abnormal Expression of Golgi Protein 73 in Clinical Values and Their Role in HBV-Related Hepatocellular Carcinoma Diagnosis and Prognosis. HEPATITIS MONTHLY 2015; 15:e32918. [PMID: 26977166 PMCID: PMC4779190 DOI: 10.5812/hepatmon.32918] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Revised: 10/22/2015] [Accepted: 11/21/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND The up-regulation of hepatic Golgi protein 73 (GP73) is associated with the progression of hepatocellular carcinoma (HCC). However, the exact mechanism and clinical values of its diagnosis and prognosis still need to be clarified. OBJECTIVES To investigate the clinical values of abnormal liver or circulating GP73 expression and their effect on HCC diagnosis and prognosis. MATERIALS AND METHODS The expression of GP73 was investigated in 88 cancerous and self-control non-cancerous tissues using tissue microarrays with immunohisto- chemistry and was confirmed by Western blotting. Circulating GP73 levels were detected in the sera of 281 patients with liver diseases using enzyme-linked immunosorbent assay. RESULTS The levels of circulating GP73 expression in the HCC group were higher than those in any group of benign liver diseases or controls. No significant difference was found between GP73 expression and patients' sex or age, tumor size, or AFP level except for those with hepatitis B virus (HBV) infection or distal metastasis (P < 0.05). The area under the receiver operating characteristic curve, sensitivity, and specificity for HCC diagnosis were 0.881, 78.34%, and 77.59% for GP73 levels over 70 μg/L or 0.754, 71.97%, and 84.48% for alpha-fetoprotein levels over 50 μg/L, respectively. The total incidence of GP73 plus alpha-fetoprotein was up to 87.26% for HCC. A positive GP73 result with brown particles was mainly located in the cytosol, with a few in the nucleus and none in the cell membrane, with abnormal expression in HCC tissues (480.7 ± 148.7) that was significantly higher (t = 10.730, P < 0.001) than those in their non-cancerous tissues (208.0 ± 66.1). The high GP73 expression in HCC was related to lymph node metastasis (χ(2) = 6.940, P = 0.008), gross classification (χ(2) = 6.311, P = 0.012), HBV (χ(2) = 4.803, P = 0.028), tumor node metastasis staging (χ(2) = 4.887, P = 0.027), and five-year survival (χ(2) = 5.206, P = 0.023). CONCLUSIONS Abnormality of hepatic or circulating GP73 expression should be regarded as an emerging biomarker for HCC diagnosis and prognosis.
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Affiliation(s)
- Wenli Sai
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Li Wang
- Medical School, Nantong University, Nantong, China
| | - Wenjie Zheng
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Junling Yang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Liuhong Pan
- Department of Oncology, Affiliated Hospital of Nantong University, Nantong, China
| | - Yin Cai
- Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China
| | - Liwei Qiu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Haijian Zhang
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Wei Wu
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
| | - Dengfu Yao
- Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, China
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Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: A comprehensive review. World J Hepatol 2015; 7:2648-2663. [PMID: 26609342 PMCID: PMC4651909 DOI: 10.4254/wjh.v7.i26.2648] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 10/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
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Affiliation(s)
- Lisa P Waller
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Vrushak Deshpande
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
| | - Nikolaos Pyrsopoulos
- Lisa P Waller, Vrushak Deshpande, Nikolaos Pyrsopoulos, Division of Gastroenterology and Hepatology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
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Wang Y, Liu T, Huang P, Zhao H, Zhang R, Ma B, Chen K, Huang F, Zhou X, Cui C, Liu X. A novel Golgi protein (GOLPH2)-regulated oncolytic adenovirus exhibits potent antitumor efficacy in hepatocellular carcinoma. Oncotarget 2015; 6:13564-78. [PMID: 25980438 PMCID: PMC4537034 DOI: 10.18632/oncotarget.3769] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2015] [Accepted: 04/10/2015] [Indexed: 12/16/2022] Open
Abstract
Golgi apparatus is the organelle mainly functioning as protein processing and secretion. GOLPH2 is a resident Golgi glycoprotein, usually called GP73. Recent data displayed that GOLPH2 is a superb hepatocellular carcinoma (HCC) marker candidate, and even its specificity is better than liver cancer marker AFP. Oncolytic adenoviruses are broadly used for targeting cancer therapy due to their selective tumor-killing effect. However, it was reported that traditionally oncolytic adenovirus lack the HCC specificity. In this study, a novel dual-regulated oncolytic adenovirus GD55 targeting HCC was first constructed based on our cancer targeted gene-viral therapeutic strategy. To verify the targeting and effectiveness of GOLPH2-regulated oncolytic adenovirus GD55 in HCC, the anticancer capacity was investigated in HCC cell lines and animal model. The results proved that the novel GOLPH2-regulated GD55 conferred higher adenovirus replication and infectivity for liver cancer cells than oncolytic adenovirus ZD55. The GOLPH2-regulated GD55 exerted a significant grow-suppressing effect on HCC cells in vitro but little damage to normal liver cells. In animal experiment, antitumor effect of GD55 was more effective in HCC xenograft of nude mice than that of ZD55. Thus GOLPH2-regulated GD55 may be a promising oncolytic virus agent for future liver cancer treatment.
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Affiliation(s)
- Yigang Wang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Tao Liu
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Panpan Huang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Hongfang Zhao
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Rong Zhang
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Buyun Ma
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Kan Chen
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Fang Huang
- School of Public Health, Zhejiang University, Hangzhou 310058, PR China
| | - Xiumei Zhou
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China
| | - Caixia Cui
- Otorhinolaryngology Head and Neck Surgery, The Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, PR China
| | - Xinyuan Liu
- Xinyuan Institute of Medicine and Biotechnology, School of Life Sciences, Zhejiang Sci-Tech University, Hangzhou 310018, PR China.,Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China
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Abstract
Liver-related biomarkers have been developed and validated mainly in patients with chronic hepatitis C for the prediction of liver fibrosis or cirrhosis, which is a final pathway of chronic liver injury. They are noninvasive, traceable, and easy-to-use. Biomarkers provide implications related to screening, diagnosis, treatment, and prognosis of chronic hepatitis. For the improvement of performance and coverage, biomarker panels, imaging biomarkers, and even genetic biomarkers have been developed. With the advancement of genomics and proteomics, earlier and more precise prediction is expected in the near future. In this review, multiple biomarker panels for the estimation of the degree of fibrosis in chronic hepatitis C, biomarkers for the screening and diagnosis of hepatitis C, biomarkers for the treatment of hepatitis C, biomarkers for the prediction of complications related to the chronic hepatitis C, and future perspectives will be summarized.
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Affiliation(s)
- Seung Ha Park
- Department of Internal Medicine, Inje University College of Medicine, Busan, South Korea
| | - Chang Seok Bang
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea.
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Liu X, Wan X, Lu S, Zhang L, Yu S, Lu X. Evaluation of a magnetic particles-based chemiluminescence enzyme immunoassay for Golgi protein 73 in human serum. Clin Chim Acta 2015; 445:54-9. [PMID: 25801213 DOI: 10.1016/j.cca.2015.03.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2014] [Revised: 03/07/2015] [Accepted: 03/09/2015] [Indexed: 12/15/2022]
Abstract
BACKGROUND Golgi protein 73 (GP73) is regarded as a potential serum biomarker for early diagnosis of hepatocellular carcinoma (HCC). We developed a rapid magnetic particles-based chemiluminescence enzyme immunoassay (MPs-CLEIA) for the determination of serum GP73. METHODS Fluorescein isothiocyanate (FITC) and alkaline phosphatase (ALP) were used to label 2 different monoclonal antibodies to GP73. Serum GP73 was captured with labeled antibodies and formed a sandwiched immunoreaction. The magnetic particles (MPs) coated with anti-FITC antibody were used as a means of separation of the GP73 protein from other serum proteins. After adding the enzyme substrate solution, the relative light unit (RLU) was measured. A MPs-CLEIA for serum GP73 was established and evaluated. RESULTS The RLU was directly proportional to the concentration of GP73. The method linearity was 5-600 μg/l. Limit of the blank was 2.19 μg/l. The intra- and inter-assay imprecision was <3% and <5%, respectively. The average recoveries were between 95% and 105%. The proposed method showed a good correlation with a commercial ELISA assay (r=0.983, p<0.001). We also evaluated the efficiency of serum GP73 measurement for the diagnosis of HCC using this assay. The area under the receiver operating characteristic curve was 0.822 (95% CI, 0.73-0.89), and the sensitivity and specificity, with cut-off value of 115.6 μg/l, were 75.4% and 92.1%, respectively. CONCLUSIONS The proposed method demonstrates an acceptable performance for quantifying serum GP73. This assay could be appropriate for routine use in clinical laboratories.
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Affiliation(s)
- Xiangyi Liu
- Department of Medical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Xiaohua Wan
- Department of Medical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Sheng Lu
- Beijing Ranos Medical Technology Co., Ltd, Beijing, PR China
| | - Lijun Zhang
- Department of Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China
| | - Shaohua Yu
- Beijing Hotgen Biotechnology Co., Ltd., Beijing, PR China
| | - Xinxin Lu
- Department of Medical Laboratory, Beijing Tongren Hospital, Capital Medical University, Beijing, PR China.
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Xia FD, Wang ZL, Chen HX, Huang Y, Li JD, Wang ZM, Li XY. Differential expression of IQGAP1/2 in Hepatocellular carcinoma and its relationship with clinical outcomes. Asian Pac J Cancer Prev 2015; 15:4951-6. [PMID: 24998570 DOI: 10.7314/apjcp.2014.15.12.4951] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To investigate IQGAP1 and IQGAP2 expression in hepatocellular carcinoma (HCC) and itsassociation with HCC clinicopathological characteristics and survival outcomes. METHODS IQGAP1 and IQGAP2 mRNA and protein were measured in HCC tissues, para-tumor tissues and normal tissues by RT-PCR and Western blotting. We further examined 150 HCC samples with adjacent para-tumor tissues and 11 normal specimens by immunohistochemistry to evaluate the correlation of IQGAP1 and IQGAP2 with clinicopathological features and prognosis. RESULTS IQGAP1 mRNA and protein were up-regulated while IQGAP2 mRNA and protein were down-regulated in human HCC tissues compared with para-tumor and normal liver tissues (p<0.05). IQGAP1 expression was higher in primary HCC (122/150, 81.3%) than matched adjacent tissues (30/150, 20%, p<0.001), whereas IQGAP2 was lower (31/150, 20.7% as compared to 112/150, 74.7%, P<0.001). Positive IQGAP1 expression correlated with larger tumor size (p=0.002), advanced TNM stage (p=0.002) and tumor differentiation (III and IV, p=0.034). Negative IQGAP2 expression was significantly associated with larger tumor size (p=0.009), multicentric tumor occurrence (p=0.01), advanced TNM stage (0.009) and tumor differentiation (III and IV, p=0.020). Survival analysis revealed that patients with either IQGAP1+ or IQGAP2- tumors had significantly reduced disease-free survival (p<0.001 and 0.006 respectively) and overall survival (p<0.001 for both). Multivariate analysis showed that IQGAP1/2 switch was an independent prognosis factor for disease-free survival (HR=2.824) and overall survival (HR=2.189). CONCLUSION Positive IQGAP1 and negative IQGAP2 expression were closely correlated with tumor progression and could be used as adjunctive biomarkers to improve prognostication for HCC patients.
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Affiliation(s)
- Fa-Da Xia
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China E-mail :
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Xu WJ, Guo BL, Han YG, Shi L, Ma WS. Diagnostic value of alpha-fetoprotein-L3 and Golgi protein 73 in hepatocellular carcinomas with low AFP levels. Tumour Biol 2014; 35:12069-74. [PMID: 25209179 DOI: 10.1007/s13277-014-2506-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Accepted: 08/14/2014] [Indexed: 12/12/2022] Open
Abstract
This study aimed to investigate the clinical values of serum alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) in the diagnosis of hepatocellular carcinoma (HCC) with low alpha-fetoprotein (AFP). From January 2011 to December 2013, 50 low-AFP HCC patients confirmed by the color Doppler flow imaging (CDFI) and pathological examinations were collected. Forty-five patients with chronic liver diseases were also selected, including 29 liver cirrhosis patients, 15 chronic hepatitis B patients, and one severe hepatitis patient. Furthermore, 100 health volunteers with no evidence of benign or malignant liver diseases were included. The enzyme-linked immunosorbent assay (ELISA) method was applied to the GP73 quantitative assay. Serum AFP concentrations were determined using immunoassays utilizing enhanced chemiluminescence. Diagnostic accuracy of GP73 and AFP-L3 assays for low-AFP HCC was evaluated using receiver operating characteristic (ROC) curve analysis. Statistical analyses were conducted with the GraphPad Prism 5.0 software. Low-AFP HCC patients (35/50) exhibited higher positive rates of AFP-L3 than non-HCC patients (5/45) and healthy controls (2/100) (both P < 0.05). There were also significant differences in the positive rate of GP73 of low-AFP HCC patients (40/50) compared to those of non-HCC patients (3/45) and healthy controls (1/100) (both P < 0.05). However, no obvious differences in the positive rates of AFP-L3 and GP73 were observed between non-HCC patients and healthy controls (both P > 0.05). ROC curves showed that the area under the curve (AUC) of AFP-L3 for the diagnosis of low-AFP HCC was 0.6994 (sensitivity [Sen] = 70.0 %, specificity [Spe] = 95.2 %, accuracy = 88.7 %), while the AUC of GP73 was 0.8411 (Sen = 80.0 %, Spe = 97.2 %, accuracy = 92.8 %). Compared with single detection, the combination of AFP-L3 and GP73 levels for the diagnosis of low-AFP HCC showed higher Sen (94.0 %), Spe (93.1 %), and better accuracy (93.3 %). Our findings provide empirical evidence that the combination of AFP-L3 and GP73 is a good diagnostic strategy for low-AFP HCC.
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Affiliation(s)
- Wan-Ju Xu
- Department of Clinical Laboratory, Qianfoshan Hospital, Jingshi Road, No. 16766, Jinan, 250014, People's Republic of China
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Wang BL, Tan QW, Gao XH, Wu J, Guo W. Elevated PIVKA-II is Associated with Early Recurrence and Poor Prognosis in BCLC 0-A Hepatocellular Carcinomas. Asian Pac J Cancer Prev 2014; 15:6673-8. [DOI: 10.7314/apjcp.2014.15.16.6673] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
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Mao R, Yang Y, Cao Q, Zhang RL, Zhang H, Xiao L, Bao YX. Significance of expression of Golgi glycoprotein 73 in hepatocellular carcinoma. Shijie Huaren Xiaohua Zazhi 2014; 22:4996. [DOI: 10.11569/wcjd.v22.i32.4996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
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