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1
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Mazidimoradi A, Sabet Birjandi S, Salehiniya H. Effect of coronavirus disease 2019 on diagnosis and treatment of hepatocellular carcinoma: a systematic review. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2023; 4:1039-1058. [PMID: 38023991 PMCID: PMC10651356 DOI: 10.37349/etat.2023.00179] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2023] [Accepted: 08/28/2023] [Indexed: 12/01/2023] Open
Abstract
Aim Changes in strategies in the coronavirus disease 2019 (COVID-19) crisis and the imposing of restrictions have isolated many vulnerable patients including those with hepatocellular carcinoma (HCC) from routine medical care. This study investigated how the COVID-19 pandemic is affecting the diagnosis and treatment of HCC. Methods An extensive search was conducted in the PubMed, Scopus, and Web of Science databases by using the appropriate keywords: COVID-19, hepatocellular carcinoma, hepatocellular cancer, and MeSH. Studies in English related to the purpose of the study were included in the analysis, and review studies, case reports, letters to editors, comments, and reports were excluded. The quality of the studies was assessed by the "Adapted Newcastle-Ottawa Quality Assessment Scales" checklist. The Endnote X7 software has been used for managing items. Results The final qualitative analysis consisted of 27 articles. During the COVID-19 crisis, HCC diagnosis decreased from 20% to 34.13% compared to pre-crisis. The impact of the COVID-19 pandemic on HCC treatment encompasses a wide range of aspects. Generally, delays in treatment for patients with HCC ranged from more than one month for 21.5% of patients in France, to two months for 26% of patients in Italy, up to 30% in Austria, and 66.7% in Asia-Pacific countries. Conclusions According to the findings, developing and implementing appropriate diagnostic and therapeutic strategies and developing low-cost and high-precision screening programs among high-risk populations seem to be effective in reducing the impact of the COVID-19 pandemic on HCC management.
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Affiliation(s)
- Afrooz Mazidimoradi
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
| | - Samane Sabet Birjandi
- Department of Midwifery, Birjand Branch Islamic Azad University, Birjand 97178-11111, Iran
| | - Hamid Salehiniya
- Social Determinants of Health Research Center, Birjand University of Medical Sciences, Birjand 97178-53577, Iran
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Maya Ramírez CE, Shokat Z, Sufyan M, Rehman MT, AlAjmi MF, Rather GM. Identification of novel scaffolds targeting SIRT3 through molecular modeling techniques for the treatment of Hepatocellular carcinoma. J Biomol Struct Dyn 2023; 42:10165-10174. [PMID: 37705289 DOI: 10.1080/07391102.2023.2256402] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 09/02/2023] [Indexed: 09/15/2023]
Abstract
Hepatocellular carcinoma is one of the top causes of cancer-related death globally. SIRT3 belongs to the Sirtuin family of proteins, a collection of NAD+-dependent enzymes that play a role in controlling several cellular functions, including metabolism, aging, and stress response. SIRT3 expression has been discovered to be often downregulated in HCC tissues relative to normal liver tissues. Hence, SIRT3 may function as a tumor suppressor in HCC. In the present study, pharmacophore-based virtual screening of a small molecule database was performed initially, and then the screened hits were docked to the active site of SIRT3 to choose the best binding modes. One co-crystal ligand (PDB name: 1NQ) was utilized as a template to generate pharmacophore model query. A total of 0.2 million compounds from the VITAS-M Lab database were downloaded and prepared for virtual screening. Following database preparation, ligand-based virtual screening was performed using the pharmacophore query model generated in the previous phase. The compounds with the same pharmacophoric characteristics as the query at the same distance were screened. There were a total of 74 hits that matched the query model. These compounds were then docked to the SIRT3 using the standard precision protocol of the glide tool. To select hits with high binding affinities, a threshold of -8 kcal/mol was used. Based on the glide gscore, two hits were chosen. These two hits were selected to investigate the stability of the protein-ligand complex by molecular dynamics simulation. All of these findings indicate that the selected hit compounds C1 and C2 can serve as lead compounds in inhibiting the biological activity of SIRT3 requiring further detailed investigations.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Carlos Eliel Maya Ramírez
- Centro de Investigación en Ciencias de la Salud (CICSA), FCS, Universidad Anáhuac México Campus Norte, Huixquilucan de Degollado, México
| | - Zeeshan Shokat
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Muhammad Sufyan
- Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan
| | - Md Tabish Rehman
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Mohamed F AlAjmi
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Gulam M Rather
- Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, USA
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3
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Wang SY, Sun K, Jin S, Wang KY, Jiang N, Shan SQ, Lu Q, Lv GY, Dong JH. Predicting the outcomes of hepatocellular carcinoma downstaging with the use of clinical and radiomics features. BMC Cancer 2023; 23:858. [PMID: 37700255 PMCID: PMC10496191 DOI: 10.1186/s12885-023-11386-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 09/07/2023] [Indexed: 09/14/2023] Open
Abstract
BACKGROUND Downstaging of hepatocellular carcinoma (HCC) makes it possible for patients beyond the criteria to have the chance of liver transplantation (LT) and improved outcomes. Thus, a procedure to predict the prognosis of the treatment is an urgent requisite. The present study aimed to construct a comprehensive framework with clinical information and radiomics features to accurately predict the prognosis of downstaging treatment. METHODS Specifically, three-dimensional (3D) tumor segmentation from contrast-enhanced computed tomography (CT) is employed to extract spatial information of the lesions. Then, the radiomics features within the segmented region are calculated. Combining radiomics features and clinical data prompts the development of feature selection to enhance the robustness and generalizability of the model. Finally, we adopt the support vector machine (SVM) algorithm to establish a classification model for predicting HCC downstaging outcomes. RESULTS Herein, a comparative study was conducted on three different models: a radiomics features-based model (R model), a clinical features-based model (C model), and a joint radiomics clinical features-based model (R-C model). The average accuracy of the three models was 0.712, 0.792, and 0.844, and the average area under the receiver-operating characteristic (AUROC) of the three models was 0.775, 0.804, and 0.877, respectively. CONCLUSIONS The novel and practical R-C model accurately predicted the downstaging outcomes, which could be utilized to guide the HCC downstaging toward LT treatment.
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Affiliation(s)
- Si-Yuan Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Kai Sun
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
- Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China
| | - Shuo Jin
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Kai-Yu Wang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Nan Jiang
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Si-Qiao Shan
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Qian Lu
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China
| | - Guo-Yue Lv
- Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China
| | - Jia-Hong Dong
- Hepatopancreatobiliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
- Research Unit of Precision hepatobiliary Surgery Paradigm, Chinese Academy of Medical Sciences, Beijing, China.
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Gillessen J, Reuken P, Hunyady PM, Reichert MC, Lothschütz L, Finkelmeier F, Nowka M, Allo G, Kütting F, Bürger M, Nierhoff D, Steffen HM, Schramm C. Evaluation of Ultrasound-based Surveillance for Hepatocellular Carcinoma in Patients at Risk: Results From a German Multicenter Retrospective Cohort Study. J Clin Transl Hepatol 2023; 11:626-637. [PMID: 36969893 PMCID: PMC10037515 DOI: 10.14218/jcth.2022.00201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Revised: 07/17/2022] [Accepted: 09/21/2022] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) surveillance in patients at risk is strongly recommended and usually performed by ultrasound (US) semiannually with or without alfa-fetoprotein (AFP) measurements. Quality parameters except for surveillance intervals have not been strictly defined. We aimed to evaluate surveillance success and risk factors for surveillance failure. METHODS Patients with ≥1 US prior to HCC diagnosis performed at four tertiary referral hospitals in Germany between 2008 and 2019 were retrospectively analyzed. Surveillance success was defined as HCC detection within Milan criteria. RESULTS Only 47% of 156 patients, median age 63 (interquartile range: 57-70) years, 56% male, and 96% with cirrhosis, received recommended surveillance modality and interval. Surveillance failure occurred in 29% and was significantly associated with lower median model for end-stage liver disease (MELD) score odds ratio (OR) 1.154, 95% confidence interval (CI): 1.027-1.297, p=0.025) and HCC localization within right liver lobe (OR: 6.083, 95% CI: 1.303-28.407, p=0.022), but not with AFP ≥200 µg/L. Patients with surveillance failure had significantly more intermediate/advanced tumor stages (93% vs. 6%, p<0.001), fewer curative treatment options (15% vs. 75%, p<0.001) and lower survival at 1 year (54% vs. 75%, p=0.041), 2 years (32% vs. 57%, p=0.019) and 5 years (0% vs. 16%, p=0.009). Alcoholic and non-alcoholic fatty liver disease (OR: 6.1, 95% CI: 1.7-21.3, p=0.005) and ascites (OR: 3.9, 95% CI: 1.2-12.6, p=0.021) were independently associated with severe visual limitations on US. CONCLUSIONS US-based HCC surveillance in patients at risk frequently fails and its failure is associated with unfavorable patient-related outcomes. Lower MELD score and HCC localization within right liver lobe were significantly associated with surveillance failure.
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Affiliation(s)
- Johannes Gillessen
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Philipp Reuken
- University Hospital Jena, Department of Internal Medicine IV - Gastroenterology, Hepatology, Infectious Disease, Jena, Germany
| | - Peter-Marton Hunyady
- University Hospital Frankfurt, Department of Internal Medicine 1 – Gastroenterology und Hepatology, Pulmonology und Allergology, Endocrinology, Frankfurt, Germany
| | | | - Lucian Lothschütz
- Department of Medicine II, Saarland University Medical Center, Homburg, Germany
| | - Fabian Finkelmeier
- University Hospital Frankfurt, Department of Internal Medicine 1 – Gastroenterology und Hepatology, Pulmonology und Allergology, Endocrinology, Frankfurt, Germany
| | - Matthias Nowka
- University Hospital Jena, Department of Internal Medicine IV - Gastroenterology, Hepatology, Infectious Disease, Jena, Germany
| | - Gabriel Allo
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Fabian Kütting
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Martin Bürger
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Dirk Nierhoff
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Hans-Michael Steffen
- University Hospital Cologne, Department of Gastroenterology and Hepatology, Cologne, Germany
| | - Christoph Schramm
- Department of Gastroenterology and Hepatology, University Hospital of Essen, Essen, Germany
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Wei L, Wang Z, Jing N, Lu Y, Yang J, Xiao H, Guo H, Sun S, Li M, Zhao D, Li X, Qi W, Zhang Y. Frontier progress of the combination of modern medicine and traditional Chinese medicine in the treatment of hepatocellular carcinoma. Chin Med 2022; 17:90. [PMID: 35907976 PMCID: PMC9338659 DOI: 10.1186/s13020-022-00645-0] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Accepted: 07/20/2022] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular carcinoma (HCC, accounting for 90% of primary liver cancer) was the sixth most common cancer in the world and the third leading cause of cancer death in 2020. The number of new HCC patients in China accounted for nearly half of that in the world. HCC was of occult and complex onset, with poor prognosis. Clinically, at least 15% of patients with HCC had strong side effects of interventional therapy (IT) and have poor sensitivity to chemotherapy and targeted therapy. Traditional Chinese medicine (TCM), as a multi-target adjuvant therapy, had been shown to play an active anti-tumor role in many previous studies. This review systematically summarized the role of TCM combined with clinically commonly used drugs for the treatment of HCC (including mitomycin C, cyclophosphamide, doxorubicin, 5-fluorouracil, sorafenib, etc.) in the past basic research, and summarized the efficacy of TCM combined with surgery, IT and conventional therapy (CT) in clinical research. It was found that TCM, as an adjuvant treatment, played many roles in the treatment of HCC, including enhancing the tumor inhibition, reducing toxic and side effects, improving chemosensitivity and prolonging survival time of patients. This review summarized the advantages of integrated traditional Chinese and modern medicine in the treatment of HCC and provides a theoretical basis for clinical research.
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Affiliation(s)
- Lai Wei
- College of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Zeyu Wang
- Department of Scientific Research, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Niancai Jing
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Yi Lu
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Jili Yang
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Hongyu Xiao
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Huanyu Guo
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Shoukun Sun
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Mingjing Li
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China
| | - Daqing Zhao
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Xiangyan Li
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China
| | - Wenxiu Qi
- Northeast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, 130117, Jilin, China.
| | - Yue Zhang
- Department of Integrated Chinese and Western Medicine, Jilin Cancer Hospital, Changchun, 130000, Jilin, China.
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Rabei R, Vakil P, King B, Lokken RP, Heller M, Fidelman N, Kohi M. Frailty as a Predictor of Complications and Transplant-Free Survival after Transarterial Chemoembolization of Hepatocellular Carcinoma. JOURNAL OF CLINICAL INTERVENTIONAL RADIOLOGY ISVIR 2022. [DOI: 10.1055/s-0042-1745775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Abstract
Abstract
Purpose To determine the association between frailty, 30-day complications, rehospitalization, and transplant-free survival (TFS) following conventional and drug-eluting bead transarterial chemoembolization.
Materials and Methods A retrospective analysis was performed on a cohort of 125 patients with treatment-naïve hepatocellular carcinoma who underwent conventional or drug-eluting beads chemoembolization at our institution between 2014 and 2015. Liver function parameters, Barcelona clinic liver cancer tumor stage, and all components of the five-item modified frailty index (mFI-5) were used to determine the patient's frailty status. Key end points included severe (grade 3 or above) adverse events of chemoembolization, 30-day rehospitalization rates, and TFS. Logistic regression analysis was performed on conventional predictors of postoperative complications after chemoembolization. Median survival was estimated and compared using the Kaplan–Meier's estimator and log-rank test.
Results Among 125 patients who underwent first-time chemoembolization, higher frailty score was an independent predictor of both 30-day hospital readmission and severe liver toxicity (p = 0.01 and p = 0.03, respectively) on multivariate logistic regression analysis. Each point increase in mFI-5 conferred a threefold or twofold increase in the risk of experiencing 30-day rehospitalization or postoperative severe adverse events, respectively. At the data censor date, patients with mFI-5 score ≥ 2 had decreased overall TFS (28.1 vs. 39.8 months, p = 0.03).
Conclusion Increasing frailty as determined by mFI-5 is an independent predictor of 30-day complications and lower TFS following chemoembolization.
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Affiliation(s)
- Rana Rabei
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - Parmede Vakil
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - Bradley King
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - R Peter Lokken
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - Michael Heller
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - Nicholas Fidelman
- Department of Interventional Radiology, University of California, San Francisco, San Francisco, California, United States
| | - Maureen Kohi
- Department of Radiology, University of North Carolina, Chapel Hill, North Carolina, United States
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Nie G, Peng D, Li B, Lu J, Xiong X. Diagnostic Accuracy of Circular RNAs in Different Types of Samples for Detecting Hepatocellular Carcinoma: A Meta-Analysis. Front Genet 2022; 12:794105. [PMID: 34992634 PMCID: PMC8724259 DOI: 10.3389/fgene.2021.794105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 11/30/2021] [Indexed: 02/05/2023] Open
Abstract
The lack of accurate biomarkers impeded the screening, diagnosis and early treatment of hepatocellular carcinoma (HCC). As a result of the development of high-throughput transcriptome analysis techniques, circular RNAs, a newly discovered class of noncoding RNAs, were recognized as potential novel biomarkers. This meta-analysis was performed to update the diagnostic roles of circular RNAs for HCC. We acquired 23 articles from PubMed, Web of Science, EMBASE, and Cochrane Library databases up to September 2021. The overall sensitivity was 0.80 (95% CI: 0.77–0.84), and the specificity was 0.83 (95% CI: 0.79–0.85), with an AUC of 0.88 (0.85–0.91). Considering of the significant heterogeneity, studies were divided into four groups based on the control types. The circular RNAs in exosomes had a sensitivity of 0.69 (95% CI: 0.61–0.75), and a highest specificity of 0.91 (95% CI: 0.83–0.96). The pooled sensitivity of circular RNAs in serum/plasma was 0.84 (95% CI: 0.81–0.87), and the pooled specificity was 0.83 (95% CI: 0.79–0.86). The pooled sensitivity of circular RNAs distinguishing tumor tissue from chronic hepatitis/cirrhosis tissues was 0.56 (95% CI: 0.48–0.64), and specificity was 0.76 (95% CI: 0.67–0.82). When the controls were adjacent tissues, the sensitivity was 0.78 (95% CI: 0.70–0.84), and the specificity was 0.78 (95% CI: 0.71–0.85). Hsa_circ_0001445 with a pooled sensitivity of 0.81, a specificity of 0.76 and an AUC of 0.85 in two studies, might be a suitable diagnostic blood biomarker for HCC. Relying on function in HCC, the AUC of subgroups were 0.88 (95%CI: 0.84–0.90) (function group) and 0.87 (95%CI: 0.84–0.90) (unknown function group). As for only reported in HCC or not, these circular RNAs had an AUC of 0.89 (95%CI: 0.86–0.91) (only in HCC) and 0.85 (95%CI: 0.82–0.88) (not only in HCC). In conclusion, the results suggested that circular RNAs were acceptable biomarkers for detecting HCC, especially those circular RNAs existing in exosomes or serum/plasma.
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Affiliation(s)
- Guilin Nie
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Dingzhong Peng
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Bei Li
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Jiong Lu
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China
| | - Xianze Xiong
- Department of Biliary Surgery, West China Hospital of Sichuan University, Chengdu, China
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Sandhu N, Rossi S. Diagnosis and Evaluation of Hepatocellular Carcinoma. HEPATO-PANCREATO-BILIARY MALIGNANCIES 2022:27-48. [DOI: 10.1007/978-3-030-41683-6_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Mullangi S, Keesari PR, Zaher A, Pulakurthi YS, Adusei Poku F, Rajeev A, Vidiyala PL, Guntupalli AL, Desai M, Ohemeng-Dapaah J, Asare Y, Patel AA, Lekkala M. Epidemiology and Outcomes of Hospitalizations Due to Hepatocellular Carcinoma. Cureus 2021; 13:e20089. [PMID: 35003948 PMCID: PMC8723719 DOI: 10.7759/cureus.20089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Accepted: 12/01/2021] [Indexed: 11/19/2022] Open
Abstract
Background Hepatocellular Carcinoma (HCC) is a severe complication of cirrhosis and the incidence of HCC has been increasing in the United States (US). We aim to describe the trends, characteristics, and outcomes of hospitalizations due to HCC across the last decade. Methods We derived a study cohort from the Nationwide Inpatient Sample (NIS) for the years 2008-2017. Adult hospitalizations due to HCC were identified using the International Classification of Diseases (9th/10th Editions) Clinical Modification diagnosis codes (ICD-9-CM/ICD-10-CM). Comorbidities were also identified by ICD-9/10-CM codes and Elixhauser Comorbidity Software (Agency for Healthcare Research and Quality, Rockville, Maryland, US). Our primary outcomes were in-hospital mortality and discharge to the facility. We then utilized the Cochran-Armitage trend test and multivariable survey logistic regression models to analyze the trends, outcomes, and predictors. Results A total of 155,436 adult hospitalizations occurred due to HCC from 2008-2017. The number of hospitalizations with HCC decreased from 16,754 in 2008 to 14,715 in 2017. Additionally, trends of in-hospital mortality declined over the study period but discharge to facilities remained stable. Furthermore, in multivariable regression analysis, predictors of increased mortality in HCC patients were advanced age (OR 1.1; 95%CI 1.0-1.2; p< 0.0001), African American (OR 1.3; 95%CI 1.1-1.4;p< 0.001), Rural/ non-teaching hospitals (OR 2.7; 95%CI 2.4-3.3; p< 0.001), uninsured (OR 1.9; CI 1.6-2.2; p< 0.0001) and complications like septicemia and pneumonia as well as comorbidities such as hypertension, diabetes mellitus, and renal failure. We observed similar trends in discharge to facilities. Conclusions In this nationally representative study, we observed a decrease in hospitalizations of patients with HCC along with in-hospital mortality; however, discharge to facilities remained stable over the last decade. We also identified multiple predictors significantly associated with increased mortality, some of which are potentially modifiable and can be points of interest for future studies.
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Affiliation(s)
| | - Praneeth R Keesari
- Internal Medicine, Kamineni Academy of Medical Sciences and Research Center, Hyderabad, IND
| | - Anas Zaher
- Internal Medicine, University of Debrecen, Debrecen, HUN
| | | | | | - Arathi Rajeev
- Internal Medicine, Government Medical College Kozhikode, Kozhikode, IND
| | | | | | - Maheshkumar Desai
- Internal Medicine, Hamilton Medical Center, Medical College of Georgia/Augusta University, Dalton, USA
| | | | - Yaw Asare
- Epidemiology and Public Health, School of Public Health, University of Ghana, Accra, GHA
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Liu J, Pei Y, Zhang Y, Wu Y, Liu F, Gu S. Predicting the prognosis of hepatocellular carcinoma with the treatment of transcatheter arterial chemoembolization combined with microwave ablation using pretreatment MR imaging texture features. Abdom Radiol (NY) 2021; 46:3748-3757. [PMID: 33386449 PMCID: PMC8286952 DOI: 10.1007/s00261-020-02891-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2020] [Revised: 11/29/2020] [Accepted: 12/04/2020] [Indexed: 02/07/2023]
Abstract
OBJECTIVE To investigate the prognostic value of baseline magnetic resonance imaging (MRI) texture analysis of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE) and microwave ablation (MWA). METHODS MRI was performed on 102 patients with HCC before receiving TACE combined with MWA in this retrospective study. The best 10 texture features were screened as a feature group for each MRI sequence by MaZda software using mutual information coefficient (MI), nonlinear discriminant analysis (NDA) and other methods. The optimal feature group with the lowest misdiagnosis rate was achieved on one MRI sequence between two groups dichotomized by 3-year survival, which was used to optimize the significant texture features with the optimal cutoff values. The Cox proportional hazards model was generated for the significant texture features and clinical variables to determine the independent predictors of overall survival (OS). The predictive performance of the model was further evaluated by the area under the ROC curve (AUC). Kaplan-Meier and log-rank tests were performed for disease-free survival (DFS) and Local recurrence-free survival (LRFS). RESULTS The optimal feature group with the lowest misdiagnosis rate of 8.82% was obtained on T2WI using MI combined with NDA feature analysis. For Cox proportional hazards regression models, the independent prognostic factors associated with OS were albumin (P = 0.047), BCLC stage (P = 0.001), Correlat(1,- 1)T2 (P = 0.01) and SumEntrp(3,0)T2 (P = 0.015), and the prediction efficiency of multivariate model is AUC = 0.876, 95%CI = 0.803-0.949. Kaplan-Meier analyses further demonstrated that BCLC (P < 0.001), Correlat(1,- 1)T2 (P = 0.023) and SumEntrp(3,0)T2 (P < 0.001) were associated with DFS, and BCLC (P = 0.007) related to LRFS. CONCLUSIONS MR imaging texture features may be used to predict the prognosis of HCC treated with TACE combined with MWA.
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Affiliation(s)
- Jun Liu
- Department of Interventional Therapy, Beijing Shijitan Hospital, Affiliated Hospital of Capital Medical University, Beijing, 100038 People’s Republic of China
| | - Yigang Pei
- Department of Radiology, Xiangya Hospital, Central South University, Changsha, 410008 Hunan People’s Republic of China
- Xiangya Hospital, Central South University, Changsha, 410008 Hunan People’s Republic of China
| | - Yu Zhang
- Department of Interventional Therapy, Beijing Shijitan Hospital, Affiliated Hospital of Capital Medical University, Beijing, 100038 People’s Republic of China
| | - Yifan Wu
- Department of Interventional Therapy, Beijing Shijitan Hospital, Affiliated Hospital of Capital Medical University, Beijing, 100038 People’s Republic of China
| | - Fuquan Liu
- Department of Interventional Therapy, Beijing Shijitan Hospital, Affiliated Hospital of Capital Medical University, Beijing, 100038 People’s Republic of China
| | - Shanzhi Gu
- Department of Interventional Therapy, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410006 Hunan People’s Republic of China
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11
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Omar SA, Attia NM, Sheir MI, Amer AS, El Shabrawy MM, Hasan BB. Is serum endocan a sensitive biomarker for early recurrence of hepatocellular carcinoma after radiofrequency ablation? Eur J Gastroenterol Hepatol 2021; 33:1015-1022. [PMID: 33867440 DOI: 10.1097/meg.0000000000002074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND AIM OF THE WORK Hepatocellular cancer (HCC) is one of the common liver cancers and considered to be the sixth most commonly occurring cancer in the world and the second leading cause of death among cancer patients. More recent studies on HCC showed that the elevated serum endocan level was a predictive factor of recurrence after radiofrequency ablation. The aim of this study is to evaluate the serum endocan level as a prognostic biomarker for recurrence of HCC after percutaneous radiofrequency ablation. PATIENTS AND METHODS Analytic-prospective study was carried out in Suez Canal University Hospitals. The study was carried out on 80 patients classified into three groups: group 1 (control group) consisted of 20 apparently healthy persons; group 2 consisted of 20 patients with liver cirrhosis; and group 3 consisted of 40 treatment-naive HCC patients who were prepared for radiofrequency ablation. All HCC patients (who were confirmed to have complete ablation after RF) were followed up by using triphasic abdominal CT, serum AFP and serum endocan assessment at 3 and 6 months after radiofrequency ablation. RESULTS Our study revealed a high level of serum endocan in the HCC group with a statistically significant difference (<0.001) between the three groups. HCC patients had a higher level of serum endocan (6.2 ± 2.25) followed by an liver cirrhosis group (2.0 ± 1.29) and then the control group (1.0 ± 0.3). The serum endocan level had a positive correlation with recurrence of HCC (P < 0.0001). There was a positive correlation between serum endocan and serum alanine transferase (P = 0.02), and a positive correlation between serum endocan and the number of tumors (P = 0.01). CONCLUSION Serum endocan is considered as a prognostic biomarker for tumor recurrence in HCC patients after radiofrequency ablation.
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Affiliation(s)
| | | | | | | | - Mohamed M El Shabrawy
- Clinical Pathology Department, Faculty of Medicine, Suez Canal University, Ismailila
| | - Basma B Hasan
- Clinical Pathology Department, Faculty of Medicine, Port Said University, port said, Egypt
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12
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Wong VCL, Wong MI, Lam CT, Lung ML, Lam KO, Lee VHF. Hallmark microRNA signature in liquid biopsy identifies hepatocellular carcinoma and differentiates it from liver metastasis. J Cancer 2021; 12:4585-4594. [PMID: 34149922 PMCID: PMC8210546 DOI: 10.7150/jca.59933] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Accepted: 05/19/2021] [Indexed: 12/25/2022] Open
Abstract
Purpose: This study aims to develop a liquid biopsy assay to identify HCC and differentially diagnose hepatocellular carcinoma (HCC) from colorectal carcinoma (CRC) liver metastasis. Methods: Thirty-two microRNAs (“HallMark-32” panel) were designed to target the ten cancer hallmarks in HCC. Quantitative PCR and supervised machine learning models were applied to develop an HCC-specific diagnostic model. One hundred thirty-three plasma samples from intermediate-stage HCC patients, colorectal cancer (CRC) patients with liver metastasis, and healthy individuals were examined. Results: Six differentially expressed microRNAs (“Signature-Six” panel) were identified after comparing HCC and healthy individuals. The microRNA miR-221-3p, miR-223-3p, miR-26a-5p, and miR-30c-5p were significantly down-regulated in the plasma of HCC samples, while miR-365a-3p and miR-423-3p were significantly up-regulated. Machine learning models combined with HallMark-32 and Signature-Six panels demonstrated promising performance with an AUC of 0.85-0.96 (p ≤ 0.018) and 0.84-0.93 (p ≤ 0.021), respectively. Further modeling improvement by adjusting sample quality variation in the HallMark-32 panel boosted the accuracy to 95% ± 0.01 and AUC to 0.991 (95% CI 0.96-1, p = 0.001), respectively. Even in alpha fetoprotein (AFP)-negative (< 20ng/mL) HCC samples, HallMark-32 still achieved 100% sensitivity in identifying HCC. The Cancer Genome Atlas (TCGA, n=372) analysis demonstrated a significant association between HallMark-32 and HCC patient survival. Conclusion: To the best of our knowledge, this is the first report to utilize circulating miRNAs and machine learning to differentiate HCC from CRC liver metastasis. In this setting, HallMark-32 and Signature-Six are promising non-invasive tests for HCC differential diagnosis and distinguishing HCC from healthy individuals.
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Affiliation(s)
- Victor Chun-Lam Wong
- OncoSeek Limited, Hong Kong Science and Technology Parks, Hong Kong Special Administrative Region, People's Republic of China
| | - Ming-In Wong
- OncoSeek Limited, Hong Kong Science and Technology Parks, Hong Kong Special Administrative Region, People's Republic of China
| | - Chi-Tat Lam
- OncoSeek Limited, Hong Kong Science and Technology Parks, Hong Kong Special Administrative Region, People's Republic of China
| | - Maria Li Lung
- Department of Clinical Oncology, LKS Faculty of Medicine, The Hong Kong Special Administrative Region, People's Republic of China
| | - Ka-On Lam
- Department of Clinical Oncology, LKS Faculty of Medicine, The Hong Kong Special Administrative Region, People's Republic of China
| | - Victor Ho-Fun Lee
- Department of Clinical Oncology, LKS Faculty of Medicine, The Hong Kong Special Administrative Region, People's Republic of China
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13
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Seo JY, Shin DW, Yu SJ, Jung JH, Han K, Cho IY, Kim SY, Choi KS, Park JH, Park JH, Kawachi I. Disparities in Liver Cancer Surveillance Among People With Disabilities: A National Database Study in Korea. J Clin Gastroenterol 2021; 55:439-448. [PMID: 32889960 DOI: 10.1097/mcg.0000000000001405] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2020] [Accepted: 07/05/2020] [Indexed: 02/08/2023]
Abstract
GOAL The goal of this study was to determine disparities in liver cancer surveillance among people with disabilities is the goal of this study. BACKGROUND Using the linked administrative database in Korea, we sought to investigate (1) whether there are disparities in liver cancer surveillance according to degree and type of disability and (2) temporal trends in liver cancer surveillance among people with disabilities. MATERIALS AND METHODS We linked national disability registration data with national cancer surveillance data. We analyzed age-standardized participation rates for each year during the 2006-2015 period according to presence, type, and severity of the disability. We also examined factors associated with liver cancer surveillance by multivariate logistic regression using the most current data (2014-2015). RESULTS The age-adjusted and sex-adjusted surveillance rate for liver cancer in people with disabilities increased from 25.7% in 2006 to 49.6% in 2015; however, during the same period, surveillance rate among people without disabilities increased from 24.9% to 54.5%. As a result, disparities in surveillance for liver cancer increased over time. The surveillance participation rate among people with disabilities was 12% lower than among people without disabilities. Surveillance rates were markedly lower among people with severe disabilities [adjusted odds ratio (aOR)=0.71] and people with renal disease (aOR=0.43), brain injuries (aOR=0.60), ostomy problems (aOR=0.60), and intellectual disabilities (aOR=0.69). CONCLUSIONS Despite the availability of a national liver cancer surveillance program, a marked disparity was found in liver cancer surveillance participation, especially among people with severe disabilities, renal disease, or brain-related or mental disabilities.
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Affiliation(s)
- Jae Youn Seo
- Department of Family Medicine/Supportive Care Center, Samsung Medical Center
| | - Dong Wook Shin
- Department of Family Medicine/Supportive Care Center, Samsung Medical Center
- Department of Digital Health, SAIHST, Sungkyunkwan University
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine
| | - Jin Hyung Jung
- Department of Medical Statistics, The Catholic University of Korea
| | - Kyungdo Han
- Department of Statistics and Actuarial Science, Soongsil University, Seoul
| | - In Young Cho
- Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine
| | - So Young Kim
- College of Medicine/Graduate School of Health Science Business Convergence, Chungbuk National University, Cheongju
| | - Kui Son Choi
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang
| | - Jong Heon Park
- Big Data Steering Department, National Health Insurance Service, Wonju, Republic of Korea
| | - Jong Hyock Park
- College of Medicine/Graduate School of Health Science Business Convergence, Chungbuk National University, Cheongju
| | - Ichiro Kawachi
- Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA
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14
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Li J, Ling W, Chen S, Yang L, Ma L, Lu Q, Luo Y. Can Risk Stratification Based on Ultrasound Elastography of Background Liver Assist CEUS LI-RADS in the Diagnosis of HCC? Front Oncol 2021; 11:662680. [PMID: 33996586 PMCID: PMC8120148 DOI: 10.3389/fonc.2021.662680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 04/16/2021] [Indexed: 02/05/2023] Open
Abstract
OBJECTIVE To explore whether risk stratification based on ultrasound elastography of liver background assists contrast-enhanced ultrasound liver imaging reporting and data system (CEUS LI-RADS) in diagnosing HCC. MATERIALS AND METHODS In total, 304 patients with focal liver lesions (FLLs) confirmed by pathology underwent CEUS and ultrasound elastography were included in this retrospective study. Patients with chronic hepatitis B (CHB, n=193) and non-CHB (n=111) were stratified by four liver stiffness measurement (LSM) thresholds. A LI-RADS category was assigned to FLLs using CEUS LI-RADS v2017. The diagnostic performance was assessed with the AUC, sensitivity, specificity, PPV, and NPV. RESULTS The mean background liver stiffness of HCC patients with CHB, HCC patients without CHB and non-HCC patients without CHB were 9.72 kPa, 8.23 kPa and 4.97 kPa, respectively. The AUC, sensitivity, specificity and PPV of CEUS LI-RADS for HCC in CHB patients with LSM ≥ 5.8 kPa, ≥ 6.8 kPa, ≥ 9.1 kPa, and ≥ 10.3 kPa were high, with corresponding values of 0.745 to 0.880, 94.2% to 95.3%, 81.3% to 85.7%, and 98.1% to 98.8%, respectively. Higher AUC and specificity for HCC was observed in non-CHB patients with LSM ≥ 9.1 kPa and ≥ 10.3 kPa compared to non-CHB patients with LSM ≥ 5.8 kPa and ≥ 6.8 kPa, with corresponding values of0.964/1.000 vs 0.590/0.580, and 100%/100% vs 60%/70%, respectively. CONCLUSION CEUS LI-RADS has a good diagnostic performance in CHB patients regardless of the background liver stiffness. Furthermore, CEUS LI-RADS can be applied for non-CHB patients with a LSM ≥ 9.1 kPa.
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Affiliation(s)
| | | | | | | | | | | | - Yan Luo
- Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China
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15
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Jia Y, Chen Y, Liu J. Prognosis-Predictive Signature and Nomogram Based on Autophagy-Related Long Non-coding RNAs for Hepatocellular Carcinoma. Front Genet 2020; 11:608668. [PMID: 33424932 PMCID: PMC7793718 DOI: 10.3389/fgene.2020.608668] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Accepted: 12/08/2020] [Indexed: 12/24/2022] Open
Abstract
Autophagy plays a vital role in hepatocellular carcinoma (HCC) pathogenesis. Long non-coding RNAs (lncRNAs) are considered regulators of autophagy, and the aim of the present study was to investigate the prognostic value of autophagy-related lncRNA (ARlncRNA) and develop a new prognostic signature to predict the 1-year and 3-year overall survival (OS) of HCC patients. Transcriptome and clinical survival information of HCC patients was obtained from The Cancer Genome Atlas database. A set of ARlncRNAs was identified by co-expression analysis, from which seven ARlncRNAs (AC005229.4, AL365203.2, AL117336.3, AC099850.3, ELFN1-AS1, LUCAT1, and AL031985.3) were selected for use as a predictive signature. Risk scores were derived for each patient, who were then divided into high-risk and low-risk groups according to the median risk value. The OS of high-risk patients was significantly lower than that of low-risk patients (P < 0.0001). The 1- and 3-year time-dependent ROC curves were used to evaluate the predictive ability of the risk score (AUC = 0.785 of 1 year, 0.710 of 3 years), and its predictive ability was found to be better than TNM stage. Moreover, the risk score was significantly, linearly related to pathological grade and TNM stage (P < 0.05). Overall, a novel nomogram to predict the 1-year and 3-year OS of HCC patients was developed, which shows good reliability and accuracy, for use in improved treatment decision-making.
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Affiliation(s)
- Yu Jia
- Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.,First Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Yan Chen
- Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.,First Clinical Medical College, Shanxi Medical University, Taiyuan, China
| | - Jiansheng Liu
- Department of General Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.,First Clinical Medical College, Shanxi Medical University, Taiyuan, China
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16
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Yu Y, Zhao Y, Zhou G, Wang X. Therapeutic Efficacy of Delta-Like Ligand 4 Gene Vaccine Overexpression on Liver Cancer in Mice. Technol Cancer Res Treat 2020; 19:1533033820942205. [PMID: 33191858 PMCID: PMC7672725 DOI: 10.1177/1533033820942205] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Delta-like ligand 4 is a notch ligand that is predominantly expressed in the endothelial tip cells and plays essential roles in the regulation of angiogenesis. In this study, we explored the therapeutic effects of delta-like ligand 4 gene vaccine overexpression on the syngeneic model mouse model of liver cancer and the underlying mechanisms. Mouse hepatocellular carcinoma cell line H22-H8D8 was used to generate subcutaneous syngeneic model liver cancer in Kunming mice, and the effects of recombinant plasmid pVAX1 containing delta-like ligand 4 vaccine on tumor growth was examined. Compared to controls, delta-like ligand 4 vaccination reduced syngeneic model tumor size by 70.31% (from 17.11 ± 9.30 cm3 to 5.08 ± 2.75 cm3, P = .035) and tumor weight by 34.19% (from 6.26 ± 3.01 g to 4.12 ± 2.52 g, P = .102), while the mouse survival was significantly increased (from 27.7 ± 6.0 days to 33.1 ± 6.1 days, P = .047). High level of delta-like ligand 4 antibody, together with a significantly increased number of CD4+ and decreased CD8+ cells were identified in the mouse peripheral blood serum samples after delta-like ligand 4 immunization. In addition, elevated serum levels of interleukin 2, interleukin 4, and interferon γ were detected in the delta-like ligand 4-vaccinated mice when compared to the controls. Further studies have revealed increased CD31 and decreased Ki67 expression in the syngeneic model tumor tissues of vaccinated mice. Taken together, our studies suggest that delta-like ligand 4 gene vaccine can inhibit the growth of hepatocellular carcinoma in mice through inhibiting tumor angiogenesis and boosting antitumor immune responses. Hence, delta-like ligand 4 gene vaccination may be a promising strategy for the treatment of transplanted liver cancer.
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Affiliation(s)
- Yi Yu
- Key Laboratory of Digestive Disease, Gansu Province, Lanzhou University Second Hospital, Lanzhou, China
| | - Yang Zhao
- Key Laboratory of Digestive System Tumors, Gansu Province, Lanzhou University Second Hospital, Lanzhou, China
| | - Guangming Zhou
- Department of Space Radiobiology, Key Laboratory of Heavy Ion Radiation Biology and Medicine, Institute of Modem Physics, Chinese Academy of Sciences, Lanzhou, China
| | - Xiang Wang
- Key Laboratory of Digestive Disease, Gansu Province, Lanzhou University Second Hospital, Lanzhou, China
- Xiang Wang, Key Laboratory of Digestive Disease, Department of Gastroenterology, Lanzhou University Second Hospital, 82 Cuiyingmen, Lanzhou 730030, China.
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17
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Janjua NZ, Wong S, Darvishian M, Butt ZA, Yu A, Binka M, Alvarez M, Woods R, Yoshida EM, Ramji A, Feld J, Krajden M. The impact of SVR from direct-acting antiviral- and interferon-based treatments for HCV on hepatocellular carcinoma risk. J Viral Hepat 2020; 27:781-793. [PMID: 32187430 DOI: 10.1111/jvh.13295] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 02/02/2020] [Accepted: 02/17/2020] [Indexed: 12/12/2022]
Abstract
We evaluated the effect of sustained virologic response (SVR) from direct-acting antiviral (DAA)- and interferon-based treatments on hepatocellular carcinoma (HCC) risk in a large population-based cohort in Canada. We used data from the BC Hepatitis Testers Cohort, which includes ~1.3 million individuals tested for HCV since 1990, linked with healthcare administrative and registry datasets. Patients were followed from the end of HCV treatment to HCC, death or 31 December 2016. We assessed HCC risk among those who did and did not achieve SVR by treatment type using proportional hazard models. Of 12 776 eligible individuals, 3905 received DAAs while 8871 received interferon-based treatments, followed for a median of 1.0 [range: 0.6-2.7] and 7.9 [range: 4.4-17.1] years, respectively. A total of 3613 and 6575 achieved SVR with DAAs- and interferon-based treatments, respectively. Among DAAs-treated patients, HCC incidence rate was 6.9 (95%CI: 4.7-10.1)/1000 person yr (PY) in SVR group (HCC cases: 26) and 38.2 (95%CI: 20.6-71.0) in the no-SVR group (HCC cases: 10, P < .001). Among interferon-treated individuals, HCC incidence rate was 1.8 (95%CI: 1.5-2.2) in the SVR (HCC cases: 99) and 13.9 (95%CI: 12.3-15.8) in the no-SVR group (HCC cases: 239, P < .001). Compared with no-SVR from interferon, SVR from DAA- and interferon-based treatments resulted in significant reduction in HCC risk (adjusted subdistribution hazard ratio (adjSHR) DAA = 0.30, 95%CI: 0.19-0.48 and adjSHR interferon = 0.2, 95%CI: 0.16-0.26). Among those with SVR, treatment with DAAs compared to interferon was not associated with HCC risk (adjSHR = 0.93, 95%CI: 0.51-1.71). In conclusion, similar to interferon era, DAA-related SVR is associated with 70% reduction in HCC risk.
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Affiliation(s)
- Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Stanley Wong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Maryam Darvishian
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.,BC Cancer, Vancouver, BC, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Mawuena Binka
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | | | - Eric M Yoshida
- Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Alnoor Ramji
- Division of Gastroenterology, University of British Columbia, Vancouver, BC, Canada
| | - Jordan Feld
- Toronto Centre for Liver Disease, Sandra Rotman Centre for Global Health, Toronto General Hospital, University of Toronto, Toronto, ON, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, BC, Canada.,Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
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18
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Abara WE, Spradling P, Zhong Y, Moorman A, Teshale EH, Rupp L, Gordon SC, Schmidt M, Boscarino JA, Daida YG, Holmberg SD. Hepatocellular Carcinoma Surveillance in a Cohort of Chronic Hepatitis C Virus-Infected Patients with Cirrhosis. J Gastrointest Cancer 2020; 51:461-468. [PMID: 31124041 PMCID: PMC6874701 DOI: 10.1007/s12029-019-00255-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Six-monthly hepatocellular carcinoma (HCC) screening in cirrhotic patients has been recommended since 2011. HCC prognosis is associated with diagnosis at an early stage. We examined the prevalence and correlates of 6-monthly HCC surveillance in a cohort of HCV-infected cirrhotic patients. METHODS Data were obtained from the medical records of patients receiving care from four hospitals between January 2011 and December 2016. Frequencies and logistic regression were conducted. RESULTS Of 2,933 HCV-infected cirrhotic patients, most were ≥ 60 years old (68.5%), male (62.2%), White (65.8%), and had compensated cirrhosis (74.2%). The median follow-up period was 3.5 years. Among these patients, 10.9% were consistently screened 6 monthly and 21.4% were never screened. Patients with a longer history of cirrhosis (AOR = 0.86, 95% CI = 0.80-0.93) were less likely to be screened 6 monthly while decompensated cirrhotic patients (AOR = 1.39, 95% CI = 1.06-1.81) and cirrhotic patients between 18 and 44 years (AOR = 2.01, 95% CI = 1.07-3.74) were more likely to be screened 6 monthly compared to compensated cirrhotic patients and patients 60 years and older respectively. There were no significant differences by race, gender, or insurance type. CONCLUSION The prevalence of consistent HCC surveillance remains low despite formalized recommendations. One in five patients was never surveilled. Patients with a longer history of cirrhosis were less likely to be surveilled consistently despite their greater HCC risk. Improving providers' knowledge about current HCC surveillance guidelines, educating patients about the benefits of consistent HCC surveillance, and systemic interventions like clinical reminders and standing HCC surveillance protocols can improve guideline-concordant surveillance in clinical practice.
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Affiliation(s)
- Winston E Abara
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA.
| | - P Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
| | - Y Zhong
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
| | - A Moorman
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
| | - E H Teshale
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
| | - L Rupp
- Henry Ford Hospital, Detroit, MI, USA
| | | | - M Schmidt
- Kaiser Permanente Northwest, Portland, OR, USA
| | | | - Y G Daida
- Kaiser Permanente, Hawaii, Honolulu, HI, USA
| | - S D Holmberg
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop G-37, Atlanta, GA, 30333, USA
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19
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Huang Y, Zeng J, Liu T, Lin X, Guo P, Zeng J, Zhou W, Liu J. Prognostic Significance of Elevated Preoperative Serum CA125 Levels After Curative Hepatectomy for Hepatocellular Carcinoma. Onco Targets Ther 2020; 13:4559-4567. [PMID: 32547086 PMCID: PMC7250700 DOI: 10.2147/ott.s236475] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Accepted: 05/07/2020] [Indexed: 12/22/2022] Open
Abstract
Objective The aim of this study was to investigate predictive and prognostic significance of elevated carbohydrate antigen 125 (CA125) serum level preoperatively. Methods A total of 3440 HCC patients were retrospectively enrolled into this study, and all of them underwent curative hepatectomy. The clinical and pathological variables together with CA125, AFP serum level were collected at diagnosis and postoperative care stages. A chi-square test was used to compare the differences between variables. Overall survival (OS) and recurrence-free survival (RFS) were measured with the Kaplan-Meier method. To estimate prognostic factors, a multivariate Cox regression analysis was performed. Results Of the 3440 enrolled patients, 409 (11.9%) exhibited elevated preoperative serum CA125 level, and high preoperative serum CA125 level was significantly associated with younger age, female, higher ALBI grade, higher serum AFP level, blood transfusion, more operative bleeding loss, larger tumor size, multiple tumor, increased macro- or micro-vascular invasion, Edmondson grade III-IV, absence of tumor capsular, satellite nodules, liver cirrhosis, more advanced TNM stages and BCLC stages. HCC patients with high preoperative serum CA125 level usually had a shorter OS rate and experienced a higher probability of recurrence than those with normal preoperative serum level of CA125 (p<0.0001). The multivariate analysis suggested that elevated serum CA125 level serves as an independent predictor of OS and RFS in HCC patients after surgical resection. Conclusion Elevated preoperative serum CA125 correlated with many malignant characterizations of HCC and served as an independent prognostic factor of OS and RFS.
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Affiliation(s)
- Yao Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People's Republic of China.,Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Jianxing Zeng
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.,Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Teng Liu
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Xinju Lin
- Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Pengfei Guo
- Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Jinhua Zeng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People's Republic of China.,Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Weiping Zhou
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, People's Republic of China
| | - Jingfeng Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, People's Republic of China.,Department of Hepatic Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.,The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China.,Southeast Big Data Institute of Hepatobiliary Health, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
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20
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Cytotoxic Activity of Aplykurodin A Isolated From Aplysia kurodai against AXIN1-Mutated Hepatocellular Carcinoma Cells by Promoting Oncogenic β-Catenin Degradation. Mar Drugs 2020; 18:md18040210. [PMID: 32294900 PMCID: PMC7230895 DOI: 10.3390/md18040210] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2020] [Revised: 04/09/2020] [Accepted: 04/11/2020] [Indexed: 11/24/2022] Open
Abstract
Dysregulation of the Wnt/β-catenin signaling pathway is involved in the development of human hepatocellular carcinoma and has thus emerged as a therapeutic target for this malignant tumor. In this study, we employed sensitive cell-based assays to identify aplykurodin A isolated from Aplysia kurodai as an antagonist of Wnt/β-catenin signaling. Aplykurodin A inhibited β-catenin responsive transcription, which was stimulated by a Wnt3a-conditioned medium or a glycogen synthase kinase 3β inhibitor by accelerating intracellular β-catenin degradation. Aplykurodin A downregulated the level of oncogenic β-catenin and decreased the expression of β-catenin-dependent gene, leading to inhibition of human hepatoma Hep3B and SNU475 cell proliferation. Moreover, apoptosis and autophagy were elicited by aplykurodin A, as indicated by an increase the number of Annexin V-FITC-stained cells and the formation of microtubule-associated protein 1 light chain 3 puncta, respectively, in Hep3B and SNU475 cells. Our findings suggest that aplykurodin A provides a novel therapeutic strategy for human hepatocellular carcinoma via stimulation of oncogenic β-catenin degradation.
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21
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Lang S, Martin A, Kasper P, Schramm C, Kütting F, Goeser T, Steffen HM, Demir M. Hepatocellular carcinoma surveillance with liver imaging is not associated with improved survival. Scand J Gastroenterol 2020; 55:222-227. [PMID: 31990240 DOI: 10.1080/00365521.2020.1718747] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Objective: International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany.Material and methods: We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis (n = 111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance (n = 290).Results: Median follow-up in the surveillance group was 76 months (range 4-310 months). Patients in the surveillance group had smaller median tumor sizes (3.5 cm vs. 4.5 cm; p < .001), fulfilled more often Milan criteria (64% vs. 42%; p < .001) and received more often liver transplantation (27% vs. 9%, p < .001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14 months in the surveillance group vs. 12 months in the non-surveillance group, p = .375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62-1.04, p = .09).Conclusions: HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.
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Affiliation(s)
- Sonja Lang
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Department of Medicine, University of California San Diego, San Diego, La Jolla, CA, USA
| | - Anna Martin
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Philipp Kasper
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Christoph Schramm
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Fabian Kütting
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Tobias Goeser
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Hans-Michael Steffen
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
| | - Münevver Demir
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.,Department of Hepatology and Gastroenterology, Campus Virchow Clinic, Charité University Medicine, Berlin, Germany
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22
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Wu G, Wu J, Pan X, Liu B, Yao Z, Guo Y, Shi X, Ding Y. Racial disparities in alpha-fetoprotein testing and alpha-fetoprotein status associated with the diagnosis and outcome of hepatocellular carcinoma patients. Cancer Med 2019; 8:6614-6623. [PMID: 31517445 PMCID: PMC6825973 DOI: 10.1002/cam4.2549] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Revised: 08/27/2019] [Accepted: 08/27/2019] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND The use of alpha-fetoprotein (AFP) testing for the surveillance, diagnosis, and prognosis of hepatocellular carcinoma (HCC) remains controversial. Here, we compared AFP testing rates, elevated AFP rates, factors associated with elevated AFP levels, and prognostic factors associated with overall survival (OS) in HCC patients from different ethnic groups. METHODS Patients with HCC were identified from the Surveillance, Epidemiology, and End Results registries. Race was categorized as white, black, and others. AFP testing rates and elevated AFP rates were analyzed. Multivariable logistic regression and Cox regression analyses were used to identify independent factors associated with elevated AFP levels and prognosis, respectively. All statistical tests were two sided. RESULTS A proportion of 79.2% of total HCC patients had AFP testing reports; 77.3% of white, 79.7% of black, and 81.2% of other races underwent AFP testing. Compared with white and other races, black HCC patients had a higher rate of elevated AFP levels among all patients and the early-stage HCC patient cohort. Elevated AFP level was a significant prognostic factor for all HCC patients in different race groups. Factors associated with elevated AFP level and prognostic factors associated with OS varied significantly by race. CONCLUSIONS AFP testing, elevated AFP rates, predictors of elevated AFP level, and prognostic factors associated with OS differed significantly according to race after adjusting for AFP levels among the three groups. AFP testing for the surveillance, diagnosis, and prognosis of HCC patients is strongly recommended, although racial disparities need to be considered.
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Affiliation(s)
- Guoyi Wu
- Department of Hepatobiliary SurgeryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina
- Clinical Medical Center for Digestive Disease of Jiangsu ProvinceNanjingJiangsuChina
| | - Jing Wu
- National Center for Chronic and Noncommunicable Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina
| | - Xiaoben Pan
- Hangzhou Key Laboratory of Inflammation and ImmunoregulationDepartment of Basic Medical ScienceSchool of MedicineHangzhou Normal UniversityHangzhouZhejiangChina
| | - Bo Liu
- Department of General SurgeryThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Zhicheng Yao
- Department of General SurgeryThe Third Affiliated Hospital of Sun Yat‐sen UniversityGuangzhouGuangdongChina
| | - Yuan Guo
- Department of Infectious DiseasesThe Second Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Xiaolei Shi
- Department of Hepatobiliary SurgeryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina
- Clinical Medical Center for Digestive Disease of Jiangsu ProvinceNanjingJiangsuChina
| | - Yitao Ding
- Department of Hepatobiliary SurgeryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsuChina
- Clinical Medical Center for Digestive Disease of Jiangsu ProvinceNanjingJiangsuChina
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23
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Xing X, Yuan H, Sun Y, Ke K, Dong X, Chen H, Liu X, Zhao B, Huang A. ANXA2 Tyr23 and FLNA Ser2152 phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis. J Proteomics 2019; 200:111-122. [PMID: 30951906 DOI: 10.1016/j.jprot.2019.03.017] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2018] [Revised: 03/15/2019] [Accepted: 03/31/2019] [Indexed: 02/06/2023]
Abstract
Hepatoma is one of the most common malignant tumors, and most patients have very poor prognosis. Early prediction and intervention of the hepatoma recurrence/metastasis are the most effective way to improve the patients' clinical outcomes. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative phospho-proteomics approach to identify biomarkers associated with hepatoma recurrence/metastasis in hepatoma cell lines with increasing metastasis ability. In total, 75 phosphorylated peptides corresponding to 60 phosphoproteins were significantly dysregulated and the participated biological processes of these phosphoproteins were tightly associated with tumor metastasis. Further signaling pathway analysis revealed that key signaling pathways which play crucial roles in cancer metastasis have been significantly over activated in the highly metastatic cells. Furthermore, the phosphorylation of FLNASer2152 and ANXA2Tyr23 were validated to be significantly up regulated in the high-metastatic cells comparing with the low-metastatic cells. By further investigation the clinical significance of the phosphorylation of FLNASer2152 and ANXA2Tyr23 in large-scale clinical samples, revealed that the over phosphorylation of FLNASer2152 and ANXA2Tyr23 were associated with poor prognosis and might be potential prognostic biomarkers for the primary hepatoma. When FLNASer2152 combined with ANXA2Tyr23, it had a better prognostic value for both OS and TTR.
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Affiliation(s)
- Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, People's Republic of China
| | - Hui Yuan
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Ying Sun
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Kun Ke
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Xiuqing Dong
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Hui Chen
- The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, People's Republic of China
| | - Bixing Zhao
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China.
| | - Aimin Huang
- The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, People's Republic of China.
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Ma B, Liu X, Yu Z. The effect of high intensity focused ultrasound on the treatment of liver cancer and patients’ immunity. Cancer Biomark 2019; 24:85-90. [PMID: 30347603 DOI: 10.3233/cbm-181822] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Baofeng Ma
- Department of Gasteroenterology, The Sixth People’s Hospital of Qingdao, Qingdao 266033, Shandong, China
- Department of Gasteroenterology, The Sixth People’s Hospital of Qingdao, Qingdao 266033, Shandong, China
| | - Xiaoming Liu
- Department of Gasteroenterology, The Sixth People’s Hospital of Qingdao, Qingdao 266033, Shandong, China
- Department of Gasteroenterology, The Sixth People’s Hospital of Qingdao, Qingdao 266033, Shandong, China
| | - Zhaoxiao Yu
- Department of Functional Examination, The Sixth People’s Hospital of Qingdao, Qingdao 266033, Shandong, China
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25
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Huang L, Zhou K, Zhang J, Ma Y, Yang W, Ran L, Jin C, Dimitrov DD, Zhu H. Efficacy and safety of high-intensity focused ultrasound ablation for hepatocellular carcinoma by changing the acoustic environment: microbubble contrast agent (SonoVue) and transcatheter arterial chemoembolization. Int J Hyperthermia 2019; 36:244-252. [PMID: 30668189 DOI: 10.1080/02656736.2018.1558290] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023] Open
Affiliation(s)
- Lihui Huang
- CountryaState Key Laboratory of Ultrasound Engineering in Medicines Co-Found by Chongqing and the Ministry of Science and Technology, College of Biomedical Engineering, Chongqing Key Laboratory of Biomedical Engineering College, Chongqing Medical University, Chongqing Collaborative Innovation Center for Minimally invasive and Noninvasive Medicine, Chongqing, China
| | - Kun Zhou
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jun Zhang
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yuhong Ma
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Yang
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Lifeng Ran
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chengbing Jin
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dobromir Dimitrov Dimitrov
- Department of Surgical Propaedeutics, Faculty of Medicine, Medical University-Pleven, Pleven, Bulgaria
- Department of Surgical Oncology, St. Marina Hospital, Medical University-Pleven, Pleven, Bulgaria
- HIFU Center, St. Marina Hospital, Medical University-Pleven, Pleven, Bulgaria
| | - Hui Zhu
- Clinical Center for Tumor Therapy of the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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26
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Kim KH, Lee SY, Hwang H, Lee JY, Ji ES, An HJ, Kim JY, Yoo JS. Direct Monitoring of Fucosylated Glycopeptides of Alpha-Fetoprotein in Human Serum for Early Hepatocellular Carcinoma by Liquid Chromatography-Tandem Mass Spectrometry with Immunoprecipitation. Proteomics Clin Appl 2018; 12:e1800062. [PMID: 29888876 DOI: 10.1002/prca.201800062] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 05/29/2018] [Indexed: 12/17/2022]
Abstract
PURPOSE Alpha-fetoprotein (AFP) is a widely used serological marker that is associated with hepatocellular carcinoma (HCC). Although the level of AFP is increased in HCC, its sensitivity for diagnosis is poor because AFP levels are also increased in liver diseases. Changes in glycoform, especially fucosylation, have been reported to be associated with the development of HCC. EXPERIMENTAL DESIGN The authors introduce the monitoring of fucosylated glycopeptides by liquid chromatography (LC)-mass spectrometry (MS) combined with immunoprecipitation, where glycan-cleaved fragments with an amino acid sequence are used as transitions. Furthermore, neuraminidase for desialylation is useful to improve the MS detection limit (limit of detection [LOD] <2 ng mL-1 ) in 0.1 μL of serum. RESULTS The performance of the relative percentage of fucosylated AFP (AFP-fuc%) for differentiating between early HCC and cirrhosis is better than that of serum AFP levels as indicated by a greater area under the receiver operator characteristic curve (area under the curve = 0.962 vs. 0.628) and sensitivity (92.3% vs. 53.9%), respectively. Furthermore, the inter- and intraday repeatability of AFP-fuc% in serum is less than 2.1%. CONCLUSIONS AND CLINICAL RELEVANCE These findings suggest that glycopeptide-based LC-MS/MS is a promising method and that AFP-fuc% is a clinically useful parameter for differentiating between early HCC and liver cirrhosis.
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Affiliation(s)
- Kwang Hoe Kim
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Soo-Youn Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea
| | - Heeyoun Hwang
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Ju Yeon Lee
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Eun Sun Ji
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Hyun Joo An
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
| | - Jin Young Kim
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
| | - Jong Shin Yoo
- Biomedical Omics Research Group, Korea Basic Science Institute, Cheongju, Ochang-eup, 28119, Republic of Korea
- Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, 34134, Republic of Korea
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27
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Hosseinzadeh F, Verdi J, Ai J, Hajighasemlou S, Seyhoun I, Parvizpour F, Hosseinzadeh F, Iranikhah A, Shirian S. Combinational immune-cell therapy of natural killer cells and sorafenib for advanced hepatocellular carcinoma: a review. Cancer Cell Int 2018; 18:133. [PMID: 30214375 PMCID: PMC6131874 DOI: 10.1186/s12935-018-0624-x] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2018] [Accepted: 08/24/2018] [Indexed: 02/06/2023] Open
Abstract
Background High prevalence of hepatocellular carcinoma (HCC) and typically poor prognosis of this disease that lead to late stage diagnosis when potentially curative therapies are least effective; therefore, development of an effective and systematic treatment is an urgent requirement. Main body In this review, several current treatments for HCC patients and their advantages or disadvantages were summarized. Moreover, various recent preclinical and clinical studies about the performances of "two efficient agents, sorafenib or natural killer (NK) cells", against HCC cells were investigated. In addition, the focus this review was on the chemo-immunotherapy approach, correlation between sorafenib and NK cells and their effects on the performance of each other for better suppression of HCC. Conclusion It was concluded that combinational therapy with sorafenib and NK cells might improve the outcome of applied therapeutic approaches for HCC patients. Finally, it was also concluded that interaction between sorafenib and NK cells is dose and time dependent, therefore, a careful dose and time optimizing is necessary for development of a combinational immune-cell therapy.
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Affiliation(s)
- Faezeh Hosseinzadeh
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Javad Verdi
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Jafar Ai
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Saieh Hajighasemlou
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.,Iran Food and Drug Administration, Tehran, Iran
| | - Iman Seyhoun
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Frzad Parvizpour
- 1Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Abolfazl Iranikhah
- 4Department of Gastroenterology, Faculty of Medicine, Qom University of Medical Sciences, Qom, Iran
| | - Sadegh Shirian
- 5Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.,6Shiraz Molecular Pathology Research Center, Dr. Daneshbod Lab, Shiraz, Iran
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28
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Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China. Sci Rep 2018; 8:12787. [PMID: 30143694 PMCID: PMC6109066 DOI: 10.1038/s41598-018-31119-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2018] [Accepted: 08/06/2018] [Indexed: 12/11/2022] Open
Abstract
Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35–64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.
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29
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Zheng Y, Yang F, Fu L, Liu K. The mechanism of miR-143 inducing apoptosis of liver carcinoma cells through regulation of the NF-κB pathway. Oncol Lett 2018; 15:9567-9571. [PMID: 29844837 PMCID: PMC5958812 DOI: 10.3892/ol.2018.8486] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2017] [Accepted: 12/01/2017] [Indexed: 01/09/2023] Open
Abstract
Primary hepatic carcinoma is a common malignant tumor with poor treatment efficacy. The effect and mechanism of miR-143 in apoptosis of liver carcinoma cells were investigated in the present study. In vitro transfection of liver carcinoma SMMC-7721 cells was performed using artificially synthesized miR-143 mimics. The proliferation of liver carcinoma cells that were treated was detected by MTT assay. Liver carcinoma cells were then stained using the Annexin V-FITC/PI method, and the apoptosis of stained liver carcinoma cells was measured using a flow cytometer. The relative mRNA expression of NF-κB p65 in the intervention and control groups was assayed using reverse transcription-quantitative polymerase chain reaction, and the protein expression of NF-κB p65 was detected using western blot analysis. The results showed that, in the intervention group, the proliferation rate of cells transfected using miR-143 mimics was significantly lower than that in the control group, the number of apoptotic SMMC-7721 cells in the intervention group increased, and the protein expression of NF-κB p65 was decreased. Thus, miR-143 may downregulate the protein expression of NF-κB p65, thereby triggering the NF-κB signaling transduction pathway inducing apoptosis of liver carcinoma cells.
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Affiliation(s)
- Yi Zheng
- Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261000, P.R. China
| | - Fan Yang
- Department of Traditional Chinese Medicine, Weifang Hi-tech Zone People's Hospital, Weifang, Shandong 261000, P.R. China
| | - Ling Fu
- Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261000, P.R. China
| | - Kang Liu
- Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261000, P.R. China
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30
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Lv SX, Qiao X. Isovitexin (IV) induces apoptosis and autophagy in liver cancer cells through endoplasmic reticulum stress. Biochem Biophys Res Commun 2018; 496:1047-1054. [PMID: 29355527 DOI: 10.1016/j.bbrc.2018.01.111] [Citation(s) in RCA: 42] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2018] [Accepted: 01/17/2018] [Indexed: 11/26/2022]
Abstract
Liver cancer is a leading cause of cancer death worldwide, and novel chemotherapeutic drugs to suppress liver cancer are urgently required. Isovitexin (IV), a glycosylflavonoid, is extracted from rice hulls of Oryza sativa, and has various biological activities. However, the anti-tumor effect of IV against liver cancer has not yet been demonstrated in vitro or in vivo. In the present study, we showed that IV significantly suppressed the growth of liver cancer cells. Mechanistic studies indicated that IV induced apoptosis by the mitochondrial apoptotic pathway, as evidenced by the increase of Bax, cleaved Caspase-3, poly (ADP-ribose) polymerase (PARP), and cytoplasm Cyto-c released from mitochondria. In addition, IV resulted in autophagy in liver cancer cells, supported by the enhancement of LC3II, autophagy-related protein (Atg) 3, Atg5 and Beclin1. Suppressing autophagy using bafilomycin A1 (BFA) or siRNA Atg-5 reduced apoptotic cells in IV-treated cells, demonstrating that autophagy induction regulated apoptosis. Moreover, IV was found to cause endoplasmic reticulum (ER) stress in liver cancer cells, along with the promotion of ER stress-related molecules, including inositol-requiring enzyme 1α (IRE1α), X-box-binding protein-1s (XBP-1s), C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP)-78. Of note, inhibition of ER stress by use of its inhibitor, tauroursodeoxycholate (TUDCA), significantly reversed IV-induced apoptosis and autophagy. In vivo, IV treatment showed significant tumor growth inhibition compared to the non-treated group. IV could therefore be a strong candidate for liver cancer prevention.
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Affiliation(s)
- Sheng-Xiang Lv
- Department of Gastroenterology, The First People's Hospital of Lianyungang, Xuzhou Medical University Affiliated Hospital of Lianyungang, Lianyungang 222002, China.
| | - Xiao Qiao
- Department of Gastroenterology, The Second People's Hospital of Huai'an, Xuzhou Medical University Affiliated Hospital of Huai'an, Huai'an 223000, China
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de Oliveira RM, Ornelas Ricart CA, Araujo Martins AM. Use of Mass Spectrometry to Screen Glycan Early Markers in Hepatocellular Carcinoma. Front Oncol 2018; 7:328. [PMID: 29379771 PMCID: PMC5775512 DOI: 10.3389/fonc.2017.00328] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2017] [Accepted: 12/21/2017] [Indexed: 12/13/2022] Open
Abstract
Association between altered glycosylation patterns and poor prognosis in cancer points glycans as potential specific tumor markers. Most proteins are glycosylated and functionally arranged on cell surface and extracellular matrix, mediating interactions and cellular signaling. Thereby, aberrant glycans may be considered a pathological phenotype at least as important as changes in protein expression for cancer and other complex diseases. As most serum glycoproteins have hepatic origin, liver disease phenotypes, such as hepatocellular carcinoma (HCC), may present altered glycan profile and display important modifications. One of the prominent obstacles in HCC is the diagnostic in advanced stages when patients have several liver dysfunctions, limiting treatment options and life expectancy. The characterization of glycomic profiles in pathological conditions by means of mass spectrometry (MS) may lead to the discovery of early diagnostic markers using non-invasive approaches. MS is a powerful analytical technique capable of elucidating many glycobiological issues and overcome limitations of the serological markers currently applied in clinical practice. Therefore, MS-based glycomics of tumor biomarkers is a promising tool to increase early detection and monitoring of disease.
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Affiliation(s)
- Raphaela Menezes de Oliveira
- Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil
| | - Carlos Andre Ornelas Ricart
- Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil
| | - Aline Maria Araujo Martins
- Laboratory of Biochemistry and Protein Chemistry, Department of Cell Biology, Institute of Biological Sciences, University of Brasilia, Brasilia, Brazil.,University Hospital Walter Cantídeo, Surgery Department, Federal University of Ceara, Fortaleza, Brazil
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St. John TM. Chronic Hepatitis. Integr Med (Encinitas) 2018. [DOI: 10.1016/b978-0-323-35868-2.00021-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Wang Z, Kang F, Gao Y, Liu Y, Xu X, Ma X, Ma W, Yang W, Wang J. Metformin Promotes 2-Deoxy-2-[18F]Fluoro-D-Glucose Uptake in Hepatocellular Carcinoma Cells Through FoxO1-Mediated Downregulation of Glucose-6-Phosphatase. Mol Imaging Biol 2017; 20:388-397. [DOI: 10.1007/s11307-017-1150-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Yokoo T, Patel AD, Lev-Cohain N, Singal AG, Yopp AC, Pedrosa I. Extrahepatic metastasis risk of hepatocellular carcinoma based on α-fetoprotein and tumor staging parameters at cross-sectional imaging. Cancer Manag Res 2017; 9:503-511. [PMID: 29081671 PMCID: PMC5652898 DOI: 10.2147/cmar.s147097] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Extrahepatic metastases have important implications in the clinical management of hepatocellular carcinoma (HCC). The purpose of this study was to validate tumor staging parameters and serum AFP as risk factors of HCC metastasis. PATIENTS AND METHODS In this retrospective case-control study, patients with a new diagnosis of HCC (N=236), median age 57 years (range 28-89 years), and male-to-female ratio of 183/53 were divided into a "no-met" group (N=101) without extrahepatic metastasis or a "met" group with extrahepatic metastases (N=135). Metastasis risk factors based on tumor staging parameters (size, number, infiltration, and vascular invasion) and serum AFP level were calculated as odds ratio (OR). Sensitivities of the risk factors as metastasis screening tests were also calculated. RESULTS AFP >400 μg/mL, index tumor size >5 cm, and vascular invasion individually had strong association with metastasis, with OR (95% confidence interval) of 11.5 (5.9-22.1), 17.7 (9.0-34.8), and 18.9 (8.2-43.9), respectively, but with moderate sensitivities as metastasis screening tests, with 71.9% (65.7-77.3), 75.6% (69.6-80.7), and 58.5% (52.1-64.7), respectively. Composite multiparametric criteria, eg, a logical union of 1) tumor size outside of Milan criteria, 2) AFP threshold >35 μg/mL, and 3) vascular invasion, had excellent OR up to 55.6 (13.0-237.1) with screening sensitivity 98.5% (95.8-99.6). CONCLUSION Serum AFP, tumor size, and vascular invasion are strongly associated with extrahepatic metastasis of HCC, especially when combined into a multiparametric metastasis prediction criterion.
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Affiliation(s)
| | | | | | | | - Adam C Yopp
- Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA
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Abstract
The current treatment modalities for patients with hepatocellular carcinoma are discussed in this review. Hepatocellular carcinoma arises in up to 90% of cirrhotic patients, mainly due to chronic viral hepatitis and alcohol abuse. Nearly two-thirds of all patients with hepatocellular carcinoma are diagnosed at advanced stages, thus causing problems with treatment. Regardless of the stage of the disease, interventional radiology offers both curative and palliative treatment options in the management of this disease. Selecting the most appropriate treatment requires an initial staging assessment and detailed clinical and radiologic workup. Treatment allocation is based on liver function, size and number of tumors, macrovascular invasion, and extrahepatic spread of disease.
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Affiliation(s)
- Fatih Boyvat
- Department of Interventional Radiology, Baskent University, Ankara, Turkey
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Singal AG, Mittal S, Yerokun OA, Ahn C, Marrero JA, Yopp AC, Parikh ND, Scaglione SJ. Hepatocellular Carcinoma Screening Associated with Early Tumor Detection and Improved Survival Among Patients with Cirrhosis in the US. Am J Med 2017; 130:1099-1106.e1. [PMID: 28213044 DOI: 10.1016/j.amjmed.2017.01.021] [Citation(s) in RCA: 98] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2016] [Revised: 12/14/2016] [Accepted: 01/24/2017] [Indexed: 12/21/2022]
Abstract
BACKGROUND Professional societies recommend hepatocellular carcinoma screening in patients with cirrhosis, but high-quality data evaluating its effectiveness to improve early tumor detection and survival in "real world" clinical practice are needed. We aim to characterize the association between hepatocellular carcinoma screening and early tumor detection, curative treatment, and overall survival among patients with cirrhosis. METHODS We performed a retrospective cohort study of patients diagnosed with hepatocellular carcinoma between June 2012 and May 2013 at 4 health systems in the US. Patients were categorized in the screening group if hepatocellular carcinoma was detected by imaging performed for screening purposes. Generalized linear models and multivariate Cox regression with frailty adjustment were used to compare early detection, curative treatment, and survival between screen-detected and non-screen-detected patients. RESULTS Among 374 hepatocellular carcinoma patients, 42% (n = 157) were detected by screening. Screen-detected patients had a significantly higher proportion of early tumors (Barcelona Clinic Liver Cancer stage A 63.1% vs 36.4%, P <.001) and were more likely to undergo curative treatment (31% vs 13%, P = .02). Hepatocellular carcinoma screening was significantly associated with improved survival in multivariate analysis (hazards ratio 0.41; 95% confidence interval, 0.26-0.65) after adjusting for patient demographics, Child-Pugh class, and performance status. Median survival of screen-detected patients was 14.6 months, compared with 6.0 months for non-screen-detected patients, with the difference remaining significant after adjusting for lead-time bias (hazards ratio 0.59, 95% confidence interval, 0.37-0.93). CONCLUSION Hepatocellular carcinoma screening is associated with increased early tumor detection and improved survival; however, a minority of hepatocellular carcinoma patients are detected by screening. Interventions to increase screening use in patients with cirrhosis may help curb hepatocellular carcinoma mortality rates.
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Affiliation(s)
- Amit G Singal
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Tex; Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Tex; Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Tex.
| | - Sahil Mittal
- Department of Internal Medicine, Baylor College of Medicine, Houston, Tex
| | - Olutola A Yerokun
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Tex
| | - Chul Ahn
- Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, Tex
| | - Jorge A Marrero
- Department of Internal Medicine, UT Southwestern Medical Center and Parkland Health and Hospital System, Dallas, Tex
| | - Adam C Yopp
- Department of Surgery, UT Southwestern Medical Center, Dallas, Tex
| | - Neehar D Parikh
- Department of Internal Medicine, University of Michigan, Ann Arbor
| | - Steve J Scaglione
- Department of Internal Medicine, Loyola University Medical Center, Maywood, Ill
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Zhao W, Qian H, Zhang R, Gao X, Gou X. MicroRNA targeting microtubule cross-linked protein (MACF1) would suppress the invasion and metastasis of malignant tumor. Med Hypotheses 2017; 104:25-29. [DOI: 10.1016/j.mehy.2017.05.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2017] [Accepted: 05/06/2017] [Indexed: 12/31/2022]
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Tong MJ, Rosinski AA, Huynh CT, Raman SS, Lu DSK. Long-term survival after surveillance and treatment in patients with chronic viral hepatitis and hepatocellular carcinoma. Hepatol Commun 2017; 1:595-608. [PMID: 29404481 PMCID: PMC5721434 DOI: 10.1002/hep4.1047] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Revised: 04/11/2017] [Accepted: 04/16/2017] [Indexed: 01/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the main cause of mortality in patients with chronic viral hepatitis (CVH). We determined the impact of surveillance and treatments on long‐term outcomes in patients with CVH who developed HCC. Between 1984 and 2014, 333 patients with HCC and with hepatitis B or hepatitis C virus infection were evaluated. An adjusted lead time bias interval was added to patients with HCC who presented with HCC (no surveillance), and their survival was compared to patients whose HCC was detected by surveillance. After HCC treatments, survival rates within and beyond 3 years of follow‐up were compared. In 175 (53%) patients, HCC was detected through surveillance using alpha‐fetoprotein and abdominal ultrasound examinations. Compared to 158 (47%) patients with HCC who had no surveillance, more patients with HCC detected by surveillance received surgical and locoregional treatments (P < 0.0001 to P < 0.001), and their 1‐, 3‐, and 5‐year overall and disease‐free survival rates were significantly higher (P < 0.001 for both). During the first 3 years of follow‐up, patients with HCC receiving liver transplantation had similar survival rates as those with liver resection or radiofrequency ablation (RFA); however, due to HCC recurrence, survival in resection and RFA patients became significantly less when followed beyond 3 years (P = 0.001 to P = 0.04). Factors associated with mortality included tumors beyond University of California at San Francisco criteria (hazard ratio [HR] 2.02; P < 0.0001), Child‐Pugh class B and C (HR, 1.58‐2.26; P = 0.043 to P = 0.015, respectively), alpha‐fetoprotein per log ng/mL increase (HR, 1.30; P < 0.0001), previous antiviral therapy in hepatitis B virus patients (HR, 0.62; P = 0.032), and treatments other than liver transplantation (HR, 2.38‐6.45; P < 0.0001 to P < 0.003). Conclusion. Patients with HCC detected by surveillance had prolonged survival. Due to HCC recurrence, survival rates after liver resection and RFA were lower when followed beyond 3 years after treatments. (Hepatology Communications 2017;1:595–608)
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Affiliation(s)
- Myron J Tong
- Liver Center, Huntington Medical Research Institutes Pasadena CA.,Pfleger Liver Institute, Division of Digestive Diseases Los Angeles CA
| | | | | | - Steven S Raman
- Department of Radiologic Sciences David Geffen School of Medicine, University of California Los Angeles CA
| | - David S K Lu
- Department of Radiologic Sciences David Geffen School of Medicine, University of California Los Angeles CA
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Physician-Patient Communication is Associated With Hepatocellular Carcinoma Screening in Chronic Liver Disease Patients. J Clin Gastroenterol 2017; 51:454-460. [PMID: 27918312 DOI: 10.1097/mcg.0000000000000747] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Patients with chronic liver disease are at high risk for developing liver cancer. Factors associated with screening awareness and doctor-patient communication regarding liver cancer were examined. STUDY Four hundred sixty-seven patients with chronic liver disease at a tertiary-care clinic participated in a phone survey regarding awareness of cancer screening, doctor-patient communication, and health behaviors. Medical records were retrospectively reviewed for data on liver disease etiology and dates of liver imaging tests. RESULTS Seventy-nine percent of patients reported awareness of liver cancer screening, and 50% reported talking to their doctor about liver cancer. Patients with higher education, abstinence from alcohol, and liver cirrhosis were more likely to be aware of liver cancer screening (P=0.06, 0.005, <0.0001). Whites, patients with higher education, and those with cirrhosis were more likely to talk to their doctor about liver cancer (P=0.006; P=0.09, <0.0001). Awareness of liver cancer screening (79%) was similar to that of colorectal cancer screening (85%), lower than breast cancer screening (91%), and higher than prostate cancer screening (66%). Patients who were aware of liver cancer screening and reported talking to their doctor about liver cancer were significantly more likely to receive consistent liver surveillance (odds ratio, 4.81; 95% confidence interval, 2.62-8.84 and odds ratio, 1.97; 95% confidence interval, 1.19-3.28, respectively). CONCLUSIONS Our study demonstrates the importance of effective physician communication with chronic liver disease patients on the risks of developing liver cancer and the importance of regular screening, especially among nonwhites and patients with lower education.
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Gopal R, Selvarasu K, Pandian PP, Ganesan K. Integrative transcriptome analysis of liver cancer profiles identifies upstream regulators and clinical significance of ACSM3 gene expression. Cell Oncol (Dordr) 2017; 40:219-233. [PMID: 28390038 DOI: 10.1007/s13402-017-0321-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/20/2017] [Indexed: 12/12/2022] Open
Abstract
PURPOSE Hepatocellular carcinoma (HCC) is one of the most common human malignancies. It has frequently been associated with metabolic perturbations and liver damages. Various members of the family of acyl-CoA synthetases are known to be involved in the production of bioactive fatty acids, and altered expression of its encoding genes has been found to be involved in metabolic perturbations. For the development of novel diagnostic and therapeutic HCC options, a fundamental understanding of the mechanisms associated with the deregulation of candidate genes involved in metabolic perturbation is required. METHODS A meta-analysis of multiple HCC mRNA profiles was performed to identify consistently deregulated genes. Expression of the acyl-CoA synthetase medium chain family member 3 (ACSM3) gene was subsequently assessed in different HCC tumor stages and correlated with various clinicopathological features. Transcription regulation, survival and pathway-associated features of the ACSM3 gene were investigated using integrative functional genomic and molecular cell biological methods. RESULTS We found that expression of the ACSM3 gene was significantly reduced in HCC tissues and was frequently downregulated in patients exhibiting high alpha-fetoprotein (AFP) levels, high alanine aminotransferase (ALT) levels, multiple nodules and large tumors. Loss of ACSM3 expression was found to correlate with advanced HCC stages and a poor survival. In addition, HNF4α was found to positively regulate the expression of the ACSM3 gene, while PPARγ was found to transcriptionally repress it. Downregulation of ACSM3 expression was perceived upon activation of the TGFβ, WNT, AKT and MYC signalling pathways. In addition, we found that ACSM3 expression correlates with fatty acid oxidation in HCC. CONCLUSION Our data provide evidence for a differential expression and regulation of the ACSM3 gene in HCC, and may lay a foundation for therapeutically targeting fatty acid metabolism in these tumors.
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Affiliation(s)
- Ramani Gopal
- Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India
| | - Karthikeyan Selvarasu
- Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India
| | - Ponmathi Panneer Pandian
- Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India
| | - Kumaresan Ganesan
- Cancer Genetics Laboratory, Department of Genetics, Centre for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625021, India.
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Janjua NZ, Chong M, Kuo M, Woods R, Wong J, Yoshida EM, Sherman M, Butt ZA, Samji H, Cook D, Yu A, Alvarez M, Tyndall M, Krajden M. Long-term effect of sustained virological response on hepatocellular carcinoma in patients with hepatitis C in Canada. J Hepatol 2017; 66:504-513. [PMID: 27818234 DOI: 10.1016/j.jhep.2016.10.028] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2016] [Revised: 10/19/2016] [Accepted: 10/22/2016] [Indexed: 01/10/2023]
Abstract
BACKGROUND & AIMS Evidence is limited on hepatocellular carcinoma (HCC) risk after sustained virological response (SVR) to interferon-based treatment of hepatitis C virus (HCV) infection. We evaluated the effect of SVR on the risk of HCC and estimated its incidence in post-SVR HCV patients from a large population-based Canadian cohort. METHODS The British Columbia Hepatitis Testers Cohort includes individuals tested for HCV between 1990-2013 linked with data on their medical visits, hospitalizations, cancers, prescription drugs and mortality. Patients receiving interferon-based HCV treatments were followed from the end of treatment to HCC diagnosis, death or December 31, 2012. We examined HCC risk among those who did and did not achieve SVR using multivariable proportional hazard models with the Fine and Gray modification for competing risks. RESULTS Of 8147 individuals who received HCV treatment and were eligible for analysis, 4663 (57%) achieved SVR and 3484 (43%) did not. Each group was followed for a median of 5.6years (range: 0.5-12.9) for an HCC incidence rate of 1.1/1000 person-years (PY) among the SVR and 7.2/1000 PY among the no SVR group. The HCC incidence rate was higher among those with cirrhosis (SVR: 6.4, no SVR: 21.0/1000 PY). In the multivariable model, SVR was associated with a lower HCC risk (subdistribution hazard ratio [SHR]=0.20, 95% CI: 0.13-0.3), while cirrhosis (SHR=2.61, 95% CI: 1.68-4.04), age ⩾50years, being male and genotype 3 infection were associated with a higher HCC risk. Among those who achieved SVR, cirrhosis, age ⩾50years and being male were associated with a higher HCC risk. CONCLUSION SVR after interferon-based treatment substantially reduces but does not eliminate HCC risk, which is markedly higher among those with cirrhosis and age ⩾50years at treatment initiation. Treatment of patients at an advanced fibrosis stage with new highly effective drugs will warrant continued surveillance for HCC post-SVR. LAY SUMMARY We assessed the effect of successful hepatitis C treatment with older interferon-based treatment on the occurrence of liver cancer (hepatocellular carcinoma) and found that successful treatment prevents liver cancer. However, more people with cirrhosis and older age continued to develop liver cancer after successful treatment. Thus, treatment with new drugs among those with cirrhosis will require continued monitoring for liver cancer.
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Affiliation(s)
- Naveed Z Janjua
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada.
| | - Mei Chong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Margot Kuo
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Ryan Woods
- British Columbia Cancer Agency, Vancouver, BC, Canada
| | - Jason Wong
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Eric M Yoshida
- Division of Gastroenterology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada
| | - Morris Sherman
- Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Zahid A Butt
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Hasina Samji
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Darrel Cook
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Amanda Yu
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Maria Alvarez
- British Columbia Centre for Disease Control, Vancouver, BC, Canada
| | - Mark Tyndall
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
| | - Mel Krajden
- British Columbia Centre for Disease Control, Vancouver, BC, Canada; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada
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Park SH, Phuc NM, Lee J, Wu Z, Kim J, Kim H, Kim ND, Lee T, Song KS, Liu KH. Identification of acetylshikonin as the novel CYP2J2 inhibitor with anti-cancer activity in HepG2 cells. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2017; 24:134-140. [PMID: 28160853 DOI: 10.1016/j.phymed.2016.12.001] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/07/2016] [Revised: 11/28/2016] [Accepted: 12/01/2016] [Indexed: 06/06/2023]
Abstract
BACKGROUND Acetylshikonin is one of the biologically active compounds derived from the root of Lithospermum erythrorhizon, a medicinal plant with anti-cancer and anti-inflammation activity. Although there have been a few previous reports demonstrating that acetylshikonin exerts anti-cancer activity in vitro and in vivo, it is still not clear what is the exact molecular target protein of acetylshikonin in cancer cells. PURPOSE The purpose of this study is to evaluate the inhibitory effect of acetylshikonin against CYP2J2 enzyme which is predominantly expressed in human tumor tissues and carcinoma cell lines. STUDY DESIGN The inhibitory effect of acetylshikonin on the activities of CYP2J2-mediated metabolism were investigated using human liver microsomes (HLMs), and its cytotoxicity against human hepatoma HepG2 cells was also evaluated. METHOD Astemizole, a representative CYP2J2 probe substrate, was incubated in HLMs in the presence or absence of acetylshikonin. After incubation, the samples were analyzed by liquid chromatography and triple quadrupole mass spectrometry. The anti-cancer activity of acetylshikonin was evaluated on human hepatocellular carcinoma HepG2 cells. WST-1, cell counting, and colony formation assays were further adopted for the estimation of the growth rate of HepG2 cells treated with acetylshikonin. RESULTS Acetylshikonin inhibited CYP2J2-mediated astemizole O-demethylation activity (Ki = 2.1µM) in a noncompetitive manner. The noncompetitive inhibitory effect of acetylshikonin on CYP2J2 enzyme was also demonstrated using this 3D structure, which showed different binding location of astemizole and acetylshikonin in CYP2J2 model. It showed cytotoxic effects against human hepatoma HepG2 cells (IC50 = 2μM). In addition, acetylshikonin treatment inhibited growth of human hepatocellular carcinoma HepG2 cells leading to apoptosis accompanied with p53, bax, and caspase3 activation as well as bcl2 down-regulation. CONCLUSION Taken together, our present study elucidates acetylshikonin displays the inhibitory effects against CYP2J2 in HLMs and anti-cancer activity in human hepatocellular carcinoma HepG2 cells.
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Affiliation(s)
- See-Hyoung Park
- Department of Bio and Chemical Engineering, Hongik University, Sejong 30016, Republic of Korea
| | - Nguyen Minh Phuc
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jongsung Lee
- Department of Genetic Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
| | - Zhexue Wu
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Jieun Kim
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Hyunkyoung Kim
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea
| | - Nam Doo Kim
- New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea
| | - Taeho Lee
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea
| | - Kyung-Sik Song
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
| | - Kwang-Hyeon Liu
- BK21 Plus KNU Multi-Omics based Creative Drug Research Team, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
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Nguyen CB, Houchen CW, Ali N. APSA Awardee Submission: Tumor/cancer stem cell marker doublecortin-like kinase 1 in liver diseases. Exp Biol Med (Maywood) 2016; 242:242-249. [PMID: 27694285 DOI: 10.1177/1535370216672746] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Liver diseases are the fourth leading cause of mortality among adults in the United States. Patients with chronic liver diseases such as viral hepatitis, fibrosis, and cirrhosis have significantly higher risks of developing hepatocellular carcinoma (HCC). With a dismal five-year survival rate of 11%, HCC is the third most common cause of cancer-related deaths worldwide. Regardless of the underlying cause, late presentation and a lack of effective therapy are the major impediments for successful treatment of HCC. Therefore, there is a considerable interest in developing new strategies for the prevention and treatment of chronic liver diseases at the early stages. Cancer stem cells (CSCs), a small cell subpopulation in a tumor, exhibit unlimited self-renewal and differentiation capacity. These cells are believed to play pivotal roles in the initiation, growth, metastasis, and drug-resistance of tumors. In this review, we will briefly discuss pivotal roles of the CSC marker doublecortin-like kinase 1 (DCLK1) in hepatic tumorigenesis. Recent evidence suggests that anti-DCLK1 strategies hold promising clinical potential for the treatment of cancers of the liver, pancreas, and colon.
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Affiliation(s)
- Charles B Nguyen
- 1 College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
| | - Courtney W Houchen
- 2 Section of Digestive Diseases and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.,3 Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK 73104, USA.,4 Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA
| | - Naushad Ali
- 2 Section of Digestive Diseases and Nutrition, Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.,3 Peggy and Charles Stephenson Cancer Center, Oklahoma City, OK 73104, USA.,4 Department of Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA
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Sheta E, El-Kalla F, El-Gharib M, Kobtan A, Elhendawy M, Abd-Elsalam S, Mansour L, Amer I. Comparison of single-session transarterial chemoembolization combined with microwave ablation or radiofrequency ablation in the treatment of hepatocellular carcinoma: a randomized-controlled study. Eur J Gastroenterol Hepatol 2016; 28:1198-1203. [PMID: 27362551 DOI: 10.1097/meg.0000000000000688] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND Globally, hepatocellular carcinoma (HCC) is the third most frequent cause of cancer-related mortality. In recent years, transarterial chemoembolization, radiofrequency ablation, and microwave ablation (MWA) have been accepted as treatment modalities for patients with surgically unresectable HCC. AIM OF THIS WORK This study aimed to compare combination treatment with radiofrequency or MWA, followed by transarterial chemoembolization, and performed in a single session. PATIENTS AND METHODS This study was carried out on 50 patients with nonresectable single-lesion HCC, who were divided into three groups: group A included 20 patients treated by transcatheter hepatic arterial chemoembolization, group B included 20 patients treated by radiofrequency thermal ablation combined with transcatheter arterial chemoembolization, and group C included 10 patients treated by MWA combined with transcatheter arterial chemoembolization. The combined treatments were performed in a single session, with the ablation performed first. RESULTS The total success rate in this study at 6 months following the procedure was 50% in group A, 70% in group B, and 80% in group C. Major complications were recorded in 22% of patients. The number of complications was the highest in group A. CONCLUSION Combined ablation with chemoembolization is superior in the treatment of nonresectable single masses larger than 4 cm. Transcatheter arterial chemoembolization and ablation can be performed safely and successfully during a single session, which has not been found to decrease the response rates to treatment. Combined treatment with MWA is more effective in terms of tumor response, and results in the same complication rate as with radiofrequency, but less than chemoembolization alone.
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Affiliation(s)
- Elshazly Sheta
- aDepartment of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, Tanta bDepartment of Radiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Xing X, Liang D, Huang Y, Zeng Y, Han X, Liu X, Liu J. The application of proteomics in different aspects of hepatocellular carcinoma research. J Proteomics 2016; 145:70-80. [PMID: 27072111 DOI: 10.1016/j.jprot.2016.03.050] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2015] [Revised: 03/23/2016] [Accepted: 03/29/2016] [Indexed: 12/12/2022]
Abstract
UNLABELLED Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, which is causing the second leading cancer-related death worldwide. With the significant advances of high-throughput protein analysis techniques, the proteomics offered an extremely useful and versatile analytical platform for biomedical researches. In recent years, different proteomic strategies have been widely applied in the various aspects of HCC studies, ranging from screening the early diagnostic and prognostic biomarkers to in-depth investigating the underlying molecular mechanisms. In this review, we would like to systematically summarize the current applications of proteomics in hepatocellular carcinoma study, and discuss the challenges of applying proteomics in study clinical samples, as well as discuss the possible application of proteomics in precision medicine. BIOLOGICAL SIGNIFICANCE In this review, we have systematically summarized the current applications of proteomics in hepatocellular carcinoma study, ranging from screening biomarkers to in-depth investigating the underlying molecular mechanisms. In addition, we have discussed the challenges of applying proteomics in study clinical samples, as well as the possible applications of proteomics in precision medicine. We believe that this review would help readers to be better familiar with the recent progresses of clinical proteomics, especially in the field of hepatocellular carcinoma research.
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Affiliation(s)
- Xiaohua Xing
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Dong Liang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; Graduate School of Fujian Medical University, Fuzhou 350018, People's Republic of China
| | - Yao Huang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China; Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Yongyi Zeng
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China; Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Xiao Han
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, People's Republic of China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China.
| | - Jingfeng Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China; Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China.
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Nguyen CB, Kotturi H, Waris G, Mohammed A, Chandrakesan P, May R, Sureban S, Weygant N, Qu D, Rao CV, Dhanasekaran DN, Bronze MS, Houchen CW, Ali N. (Z)-3,5,4'-Trimethoxystilbene Limits Hepatitis C and Cancer Pathophysiology by Blocking Microtubule Dynamics and Cell-Cycle Progression. Cancer Res 2016; 76:4887-96. [PMID: 27287718 DOI: 10.1158/0008-5472.can-15-2722] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Accepted: 06/05/2016] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Chronic hepatitis C virus (HCV) infection causes induction of several tumors/cancer stem cell (CSC) markers and is known to be a major risk factor for development of HCC. Therefore, drugs that simultaneously target viral replication and CSC properties are needed for a risk-free treatment of advanced stage liver diseases, including HCC. Here, we demonstrated that (Z)-3,5,4'-trimethoxystilbene (Z-TMS) exhibits potent antitumor and anti-HCV activities without exhibiting cytotoxicity to human hepatocytes in vitro or in mice livers. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl4) extensively induced expression of DCLK1 (a CSC marker) in the livers of C57BL/6 mice following hepatic injury. Z-TMS exhibited hepatoprotective effects against DEN/CCl4-induced injury by reducing DCLK1 expression and improving histologic outcomes. The drug caused bundling of DCLK1 with microtubules and blocked cell-cycle progression at G2-M phase in hepatoma cells via downregulation of CDK1, induction of p21(cip1/waf1) expression, and inhibition of Akt (Ser(473)) phosphorylation. Z-TMS also inhibited proliferation of erlotinib-resistant lung adenocarcinoma cells (H1975) bearing the T790M EGFR mutation, most likely by promoting autophagy and nuclear fragmentation. In conclusion, Z-TMS appears to be a unique therapeutic agent targeting HCV and concurrently eliminating cells with neoplastic potential during chronic liver diseases, including HCC. It may also be a valuable drug for targeting drug-resistant carcinomas and cancers of the lungs, pancreas, colon, and intestine, in which DCLK1 is involved in tumorigenesis. Cancer Res; 76(16); 4887-96. ©2016 AACR.
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Affiliation(s)
- Charles B Nguyen
- College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Hari Kotturi
- Department of Biology, University of Central Oklahoma, Edmond, Oklahoma
| | - Gulam Waris
- Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois
| | - Altaf Mohammed
- College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Center for Cancer Prevention and Drug Development, Hematology-Oncology Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Parthasarathy Chandrakesan
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma
| | - Randal May
- Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma
| | - Sripathi Sureban
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma
| | - Nathaniel Weygant
- Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Dongfeng Qu
- Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma
| | - Chinthalapally V Rao
- College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Center for Cancer Prevention and Drug Development, Hematology-Oncology Section, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Danny N Dhanasekaran
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Michael S Bronze
- Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma
| | - Courtney W Houchen
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma.
| | - Naushad Ali
- Peggy and Charles Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Medicine, Section of Digestive Diseases and Nutrition, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma. Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma.
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Guan X, Gao M, Xu H, Zhang C, Liu H, Lv L, Deng S, Gao D, Tian Y. Quercetin-loaded poly (lactic-co-glycolic acid)-d-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles for the targeted treatment of liver cancer. Drug Deliv 2016; 23:3307-3318. [DOI: 10.1080/10717544.2016.1176087] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Affiliation(s)
- Xin Guan
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Meng Gao
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Hong Xu
- College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Chenghong Zhang
- College of Basic Medical Sciences, Dalian Medical University, Dalian, China
| | - Hongyan Liu
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Li Lv
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Sa Deng
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Dongyan Gao
- College of Pharmacy, Dalian Medical University, Dalian, China and
| | - Yan Tian
- College of Pharmacy, Dalian Medical University, Dalian, China and
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The role of 90Y-radioembolization in downstaging primary and secondary hepatic malignancies: a systematic review. Clin Transl Imaging 2016; 4:283-295. [PMID: 27512689 PMCID: PMC4960274 DOI: 10.1007/s40336-016-0172-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2016] [Accepted: 03/14/2016] [Indexed: 12/11/2022]
Abstract
Radioembolization (RE) is an emerging treatment strategy for patients with primary hepatic malignancies and metastatic liver disease. Though RE is primarily performed in the palliative setting, a shift toward the curative setting is seen. Currently, hepatic resection and in selected cases liver transplantation are the only curative options for patients with a hepatic malignancy. Unfortunately, at diagnosis most patients are not eligible for liver surgery due to the imbalance between the necessary liver resection and the remaining liver remnant. However, in borderline resectable cases, tumor volume reduction and/or increasing the future liver remnant can lead to a resectable situation. The combination of selective tumor treatment, the induction of hypertrophy of untreated liver segments, and its favourable toxicity profile make RE an appealing strategy for downstaging. The present review discusses the possibilities for RE in the preoperative setting as a downstaging tool or as a bridge to liver transplantation.
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Cross TJS, Villanueva A, Shetty S, Wilkes E, Collins P, Adair A, Jones RL, Foxton MR, Meyer T, Stern N, Warshow U, Khan N, Prince M, Khakoo S, Alexander GJ, Khan S, Reeves H, Marshall A, Williams R. A national survey of the provision of ultrasound surveillance for the detection of hepatocellular carcinoma. Frontline Gastroenterol 2016; 7:82-89. [PMID: 28840911 PMCID: PMC5369506 DOI: 10.1136/flgastro-2015-100617] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 08/19/2015] [Accepted: 09/11/2015] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Hepatocellular carcinoma (HCC), the sixth most common cancer worldwide and third most common cause of cancer related death, is closely associated with the presence of cirrhosis. Survival is determined by the stage of the cancer, with asymptomatic small tumours being more amenable to treatment. Early diagnosis is dependent on regular surveillance and the primary objective of this survey was to gain a better understanding of the baseline attitudes towards and provision of ultrasound surveillance (USS) HCC surveillance in the UK. In addition, information was obtained on the stages of cancer of the patients being referred to and discussed at regional multidisciplinary team meetings. DESIGN UK hepatologists, gastroenterologists and nurse specialists were sent a questionnaire survey regarding the provision of USS for detection of HCC in their respective hospitals. RESULTS Provision of surveillance was poor overall, with many hospitals lacking the necessary mechanisms to make abnormal results, if detected, known to referring clinicians. There was also a lack of standard data collection and in many hospitals basic information on the number of patients with cirrhosis and how many were developing HCC was not known. For the majority of new HCC cases was currently being made only at an incurable late stage (60%). CONCLUSIONS In the UK, the current provision of USS based HCC surveillance is poor and needs to be upgraded urgently.
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Affiliation(s)
- T J S Cross
- Department of Hepatology, The Royal Liverpool Hospital, Liverpool, UK
| | - A Villanueva
- Institute of Liver Studies, Kings College Hospital, London, UK
| | - S Shetty
- The Liver Unit, Queen Elizabeth Hospital II Hospital, Birmingham, UK
| | - E Wilkes
- Digestive Diseases Unit, Queens Medical Centre, Nottingham, UK
| | - P Collins
- Department of Hepatology, Bristol Royal Infirmary, Bristol, UK
| | - A Adair
- Scottish Liver Transplant Unit, Edinburgh, UK
| | - R L Jones
- Department of Hepatology and Liver Transplantation, St James University Hospital, Leeds, UK
| | - M R Foxton
- Department of Gastroenterology, Chelsea and Westminster Hospital, Liverpool, UK
| | - T Meyer
- Department of Oncology, The Royal Free Hospital, London, UK
| | - N Stern
- Department of Hepato-Biliary Medicine, Aintree University Hospital, Liverpool, UK
| | - U Warshow
- The Southwest Liver Unit, Derriford Hospital, Plymouth, UK
| | - N Khan
- The Royal Marsden Hospital, London, UK
| | - M Prince
- Department of Gastroenterology and Hepatology, Manchester, UK
| | - S Khakoo
- Department of Academic and Translational Medicine, University of Southampton, Southampton, UK
| | - G J Alexander
- Department of Hepatology and Liver Transplant Medicine, Addenbrooke's Hospital, Cambridge, UK
| | - S Khan
- The Liver Unit, St Mary Hospital, London, UK
| | - H Reeves
- Department of Hepatology and Liver Transplantation, Freeman Hospital, Newcastle-on-Tyne, UK
| | - Aileen Marshall
- The Sheila Sherlock Liver Centre, The Royal Free Hospital, London, UK
| | - R Williams
- Institute of Hepatology, Foundation for Liver Research, London, UK
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Xing X, Huang Y, Wang S, Chi M, Zeng Y, Chen L, Li L, Zeng J, Lin M, Han X, Liu X, Liu J. Comparative analysis of primary hepatocellular carcinoma with single and multiple lesions by iTRAQ-based quantitative proteomics. J Proteomics 2015; 128:262-271. [PMID: 26300425 DOI: 10.1016/j.jprot.2015.08.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2014] [Revised: 07/16/2015] [Accepted: 08/12/2015] [Indexed: 02/07/2023]
Abstract
In clinical practices, the therapeutic outcomes and prognosis of hepatocellular carcinoma (HCC) patients with different tumor numbers after surgery are very different; however, the underlying mechanisms of the tumorigenesis and development of HCC with different tumor numbers are still not well understood. Here, we systematically compared the overall proteome profiles between the primary HCC with single and multiple lesions using iTRAQ-based quantitative proteomics approach. We identified that 107 and 330 proteins were dysregulated in HCC tissue with multiple lesions (MC group) and HCC tissue with a single lesion (SC group), compared with their non-cancerous tissue (MN and SN groups) respectively. The dysregulated proteins in MC group are concentrated in UBC signaling pathway and NFκB signaling pathway, but the dysregulated proteins in SC group are more concentrated in ERK signaling pathway and the NFκB signaling pathway. These information revealed that there might be different molecular mechanisms of the tumorigenesis and development of the HCC with single and multiple lesions. Furthermore, HSD17B13 were only down-regulated in MC group while HK2 were only up-regulated in SC group among these dysregulated proteins. Therefore, the protein HSD17B13 and HK2 might be potential biomarkers for the primary HCC with single and multiple lesions.
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Affiliation(s)
- Xiaohua Xing
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Yao Huang
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China
| | - Sen Wang
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Minhui Chi
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Yongyi Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Lihong Chen
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Ling Li
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Jinhua Zeng
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Minjie Lin
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China
| | - Xiao Han
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing 100081, People's Republic of China
| | - Xiaolong Liu
- The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China.
| | - Jingfeng Liu
- Liver Disease Center, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China; The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People's Republic of China.
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