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Ding Y, Yu Y. Therapeutic potential of flavonoids in gastrointestinal cancer: Focus on signaling pathways and improvement strategies (Review). Mol Med Rep 2025; 31:109. [PMID: 40017144 PMCID: PMC11884236 DOI: 10.3892/mmr.2025.13474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/30/2025] [Indexed: 03/01/2025] Open
Abstract
Flavonoids are a group of polyphenolic compounds distributed in vegetables, fruits and other plants, which have considerable antioxidant, anti‑tumor and anti‑inflammatory activities. Several types of gastrointestinal (GI) cancer are the most common malignant tumors in the world. A large number of studies have shown that flavonoids have inhibitory effects on cancer, and they are recognized as a class of potential anti‑tumor drugs. Therefore, the present review investigated the molecular mechanisms of flavonoids in the treatment of different types of GI cancer and summarized the drug delivery systems commonly used to improve their bioavailability. First, the classification of flavonoids and the therapeutic effects of various flavonoids on human diseases were briefly introduced. Then, to clarify the mechanism of action of flavonoids on different types of GI cancer in the human body, the metabolic process of flavonoids in the human body and the associated signaling pathways causing five common types of GI cancer were discussed, as well as the corresponding therapeutic targets of flavonoids. Finally, in clinical settings, flavonoids have poor water solubility, low permeability and inferior stability, which lead to low absorption efficiency in vivo. Therefore, the three most widely used drug delivery systems were summarized. Suggestions for improving the bioavailability of flavonoids and the focus of the next stage of research were also put forward.
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Affiliation(s)
- Ye Ding
- Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
| | - Yong Yu
- Henan Key Laboratory of Helicobacter Pylori and Microbiota and Gastrointestinal Cancer, Marshall Medical Research Center, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
- Department of Gastroenterology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
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De-Armas-Conde N, González-Rico FJ, Jaén-Torrejimeno I, Merino JM, López-Guerra D, Ordiales-Talavero A, Rojas-Holguín A, Marín-Díaz B, Ramón-Rodríguez J, Ordóñez-Mata L, Fernández-Salguero PM, Blanco-Fernández G. Involvement of β-catenin expression in hepatocellular carcinoma prognosis in a cohort of patients undergoing curative treatment. Surgery 2025; 178:108885. [PMID: 39448327 DOI: 10.1016/j.surg.2024.09.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 09/19/2024] [Accepted: 09/22/2024] [Indexed: 10/26/2024]
Abstract
BACKGROUND Hepatocellular carcinoma is a tumor of epithelial origin that arises from the action of different carcinogens on the hepatocytes and has a high worldwide incidence. The prognostic markers of this disease have not been completely established. Mutations in the gene encoding β-catenin are overexpressed in hepatocellular carcinoma. The objective of our study was to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the already known prognostic markers. METHODS We conducted an observational and prospective cohort study on adult patients diagnosed with hepatocellular carcinoma from whom samples of nontumor and tumor liver parenchyma were taken intraoperatively to correlate the molecular expression of β-catenin in hepatocellular carcinoma with the known prognostic markers. RESULTS A total of 81 samples were collected, of which 48 met the inclusion criteria. The final sample was divided into patients with a diagnosis of hepatocellular carcinoma on a cirrhotic liver, corresponding to 31 patients (64.6%), and patients with a diagnosis of hepatocellular carcinoma on a noncirrhotic liver, corresponding to 17 patients (35.4%). We found that overexpression of β-catenin and the neutrophil/lymphocyte ratio are independently related to disease-free survival, and both overexpression and molecular repression of β-catenin are independently related. CONCLUSION Molecular overexpression of β-catenin in hepatocellular carcinoma compared with nontumor tissue is associated with worse disease-free survival, and its combination with a high neutrophil-lymphocyte ratio worsens this prognosis.
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Affiliation(s)
- Noelia De-Armas-Conde
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain
| | - Francisco Javier González-Rico
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Isabel Jaén-Torrejimeno
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Jaime M Merino
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Diego López-Guerra
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain; Universidad de Extremadura, Facultad de Medicina y Ciencias de la Salud, Badajoz, Spain
| | - Ana Ordiales-Talavero
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Adela Rojas-Holguín
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain; Universidad de Extremadura, Facultad de Medicina y Ciencias de la Salud, Badajoz, Spain
| | - Beatriz Marín-Díaz
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Julen Ramón-Rodríguez
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain
| | - Laura Ordóñez-Mata
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Pedro M Fernández-Salguero
- Facultad de Ciencias, Departamento de Bioquímica y Biología Molecular y Genética, Universidad de Extremadura, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain
| | - Gerardo Blanco-Fernández
- Department of Hepato-pancreatic-biliary Surgery and Liver Transplantation. Hospital Universitario de Badajoz, Badajoz, Spain; Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Campus de Badajoz, Badajoz, Spain; Universidad de Extremadura, Facultad de Medicina y Ciencias de la Salud, Badajoz, Spain.
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Abdelmalak J, Lubel JS, Sinclair M, Majeed A, Kemp W, Roberts SK. Quality of care in hepatocellular carcinoma-A critical review. Hepatol Commun 2025; 9:e0595. [PMID: 39665645 PMCID: PMC11637749 DOI: 10.1097/hc9.0000000000000595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Accepted: 10/16/2024] [Indexed: 12/13/2024] Open
Abstract
There is significant variation in HCC management across different centers with poor adherence to evidence-based clinical practice guidelines as assessed in prior studies. In Australia, quality indicators (QIs) have recently been proposed by a multidisciplinary group of experts to help provide a framework to assess and monitor the quality of HCC care. In this review, we discuss the many areas where real-world practice deviates from evidence-based medicine, the role that QI sets play in addressing this gap, and the similarities and differences between Australian QIs and other leading treatment guidelines and QI sets from around the world. We focus on the utility of QI sets to identify opportunities for targeted improvement in the real-world clinical environment. We conclude with a discussion about the formation of a national clinical quality registry as a long-term measure to facilitate continual improvements in patient care within and across sites in order to optimize patient outcomes.
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Affiliation(s)
- Jonathan Abdelmalak
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
- Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia
| | - John S. Lubel
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Marie Sinclair
- Victorian Liver Transplant Unit, Austin Health, Heidelberg, Victoria, Australia
- Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
| | - Stuart K. Roberts
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
- School of Translational Medicine, Monash University, Melbourne, Victoria, Australia
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Somers N, Butaye E, Grossar L, Pauwels N, Geerts A, Raevens S, Lefere S, Devisscher L, Meuris L, Callewaert N, Vlierberghe HV, Verhelst X. Glycomics as prognostic biomarkers of hepatocellular carcinoma: A systematic review. Oncol Lett 2025; 29:24. [PMID: 39530005 PMCID: PMC11551839 DOI: 10.3892/ol.2024.14769] [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: 03/13/2024] [Accepted: 09/10/2024] [Indexed: 11/16/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, which is associated with a low 5-year survival rate. The importance of effective disease monitoring and prognostic evaluation is undeniable. For the present study, a systematic review was performed using extensive searches in Medline, Embase, Web of Science and Scopus up to December 29, 2023. The aim of the present study was to examine whether N-glycomics could predict the risk of developing HCC in adults with chronic liver disease and, if HCC was present, predict overall survival. As a secondary outcome, the prediction capability of HCC recurrence was assessed. After deduplication, 3,904 studies were identified, of which 30 were included. Overall, the median size of the study cohort was 144 patients, with a median follow-up time of 63.6 months. Three studies explored N-glycomics in whole serum, whereas the rest focused on individual glycoproteins, with Mac-2 binding protein glycosylation isomer (M2BPGi) being the most commonly studied. Most articles investigated baseline M2BPGi values as predictors for the development of HCC and demonstrated a median area under the curve of 0.83 with a cut-off index value of 1.8. In conclusion, it was revaled that N-glycan changes exhibit added value in determining patient prognosis in terms of survival, monitoring HCC development and recurrence.
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Affiliation(s)
- Nicky Somers
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Emma Butaye
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Lorenz Grossar
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Nele Pauwels
- Knowledge Center for Health Ghent, Ghent University, Ghent University Hospital, 9000 Ghent, Belgium
| | - Anja Geerts
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Sarah Raevens
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Sander Lefere
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacy Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Lindsey Devisscher
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
- Department of Basic and Applied Medical Sciences, Gut-Liver Immunopharmacy Unit, Faculty of Medicine and Health Sciences, Ghent University, 9000 Ghent, Belgium
| | - Leander Meuris
- Department of Biochemistry and Microbiology, VIB-UGent Center for Biotechnology, 9000 Ghent, Belgium
- Department of Biochemistry and Microbiology, Ghent University, 9000 Ghent, Belgium
| | - Nico Callewaert
- Department of Biochemistry and Microbiology, VIB-UGent Center for Biotechnology, 9000 Ghent, Belgium
- Department of Biochemistry and Microbiology, Ghent University, 9000 Ghent, Belgium
| | - Hans Van Vlierberghe
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
| | - Xavier Verhelst
- Department of Gastroenterology and Hepatology, Ghent University Hospital, 9000 Ghent, Belgium
- Hepatology Research Unit, Liver Research Center Ghent, Ghent University, 9000 Ghent, Belgium
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Pol S. [Hepatocellular carcinoma (HCC)]. MEDECINE TROPICALE ET SANTE INTERNATIONALE 2024; 4:mtsi.v4i4.2024.614. [PMID: 40070978 PMCID: PMC11892391 DOI: 10.48327/mtsi.v4i4.2024.614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Accepted: 10/15/2024] [Indexed: 03/14/2025]
Abstract
Primary liver cancers are tumors that develop from different liver cells. Hepatocellular carcinoma (HCC), which develops from hepatocytes, accounts for approximately 75-85% of primary liver cancers.HCC is the 6th leading cause of cancer worldwide and the 3rd leading cause of cancer-related death. Its incidence is low in northern Europe, but high in sub-Saharan Africa and the Far East, where both hepatotropic viruses and exposure to mycotoxins are. It complicates cirrhosis in over 90% of cases and is predominantly male.The prevalence of HCC is increasing due to improved diagnostic techniques and criteria, but also to the persistence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in adults. A worldwide increase in the incidence of steatopathy makes it the leading cause of liver disease worldwide, associated with alcohol abuse and/or steatohepatitis associated with metabolic dysfunction (MASH), including type 2 diabetes.Chronic hepatotropic viral infections, cirrhosis and chemical carcinogens combine to produce an annual incidence of 2-5% of hepatocellular carcinoma arising from cirrhosis. This justifies biannual surveillance of known cirrhosis, without which late diagnosis limits therapeutic options.Major advances have been made in curative treatment (liver transplantation, surgery, radiodestruction) and palliative treatment (chemo- or radioembolization, sorafenib chemotherapy or immunotherapy), depending on how early HCC is diagnosed (size, number of hepatic or extrahepatic lesions) and the severity of underlying liver disease and associated comorbidities.
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Affiliation(s)
- Stanislas Pol
- AP-HP. Centre Université Paris Centre, Groupe hospitalier Cochin Port Royal, Département médical universitaire de Cancérologie et spécialités médico-chirurgicales, Service des maladies du foie, Paris, France; Université Paris Cité, F-75006, Paris, France
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Patresan J, Patel H, Chandrasekaran K, Reynolds G. Current Treatment Paradigm and Approach to Advanced Hepatocellular Carcinoma. Cureus 2024; 16:e75471. [PMID: 39791050 PMCID: PMC11717138 DOI: 10.7759/cureus.75471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/09/2024] [Indexed: 01/12/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common forms of primary liver cancer worldwide. Herein, we present a review article that provides a broad overview of the current landscape of HCC, including the etiology, potential risk factors, and molecular pathways that can serve as potential therapeutic targets. The risk factors tend to vary depending on the geographic distribution; hepatitis B-induced cirrhosis and HCC occur more frequently in Asia and Sub-Saharan Africa, whereas metabolic disorders are the culprits in Western Europe and the Americas. The exact molecular alterations that drive hepatocarcinogenesis have yet to be elucidated; however, a complex interplay exists between oxidative stress and chronic inflammation. Diagnostic modalities such as tri-phasic MRI or CT also have distinct patterns for HCC, which aid significantly in diagnosis. Furthermore, the review aims to highlight treatment strategies, including transplantation, locoregional radiation therapies, and interventional radiological techniques such as chemotherapy or radioembolization. Finally, systemic therapies will be discussed, taking advantage of molecular pathways that influence cellular proliferation and survival as well as immunotherapy.
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Affiliation(s)
- John Patresan
- Hematology and Oncology, Roger Williams Medical Center, Boston University School of Medicine, Providence, USA
| | - Harsh Patel
- Gastroenterology and Hepatology, New York-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, Brooklyn, USA
| | - Karthik Chandrasekaran
- Internal Medicine and Gastroenterology, New York-Presbyterian Brooklyn Methodist Hospital, Weill Cornell Medicine, Brooklyn, USA
| | - Griffin Reynolds
- Hematology and Oncology, Roger Williams Medical Center, Boston University School of Medicine, Providence, USA
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Ding S, Ding W, Zhang Y, Chen Y, Tang H, Jiang X, Chen J. Serum HIF-1α, IGF-1 and IGFBP-3 correlate to recurrence and overall survival in early-stage hepatocellular carcinoma patients. Biomark Med 2024; 18:1027-1036. [PMID: 39552593 PMCID: PMC11633424 DOI: 10.1080/17520363.2024.2421149] [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: 06/19/2024] [Accepted: 10/22/2024] [Indexed: 11/19/2024] Open
Abstract
Aim: Recurrence of hepatocellular carcinoma (HCC) after ultrasound-guided microwave ablation (UGMWA) was a critical issue. Therefore, it is significant to identify the role of hypoxia-inducible factor 1 α (HIF-1α), insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in recurrence.Materials & methods: HCC patients receiving UGMWA were divided into recurrence and no-recurrence groups. The preoperative and postoperative risk factors were compared between these two groups.Results: Preoperative and postoperative serum levels of HIF-1α, IGF-1 and IGFBP-3 were closely associated with the recurrence of HCC. Serum HIF-1α level was increased, while serum levels of IGF-1 and IGFBP-3 were decreased in HCC patients with recurrence.Conclusion: HIF-1α, IGF-1 and IGFBP-3 were associated with and predicted the recurrence of HCC after UGMWA, respectively or in combination.
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Affiliation(s)
- Shujun Ding
- Department of Ultrasonography, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
| | - Wei Ding
- Department of Interventional Radiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
| | - Ye Zhang
- Department of General Surgery, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
| | - Yunbao Chen
- Department of Ultrasonography, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
| | - Hongtao Tang
- Department of Ultrasonography, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
| | - Xiao Jiang
- Department of Ultrasonography, Shanghai Yangpu District Shidong Hospital, No. 999 Shiguang Road, Shanghai, 200438, China
| | - Jun Chen
- Department of Ultrasonography, Wuxi People's Hospital Affiliated to Nanjing Medical University, Qingyang Road, Wuxi, 214023, Jiangsu, China
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Duduyemi OP, Potapenko K, Limanska N, Kotsyuda S, Petriv N, Suo H, Gudzenko T, Ivanytsia V, Yevsa T. Lactiplantibacillus plantarum inhibited the growth of primary liver cancer by inducing early apoptosis and senescence, in vitro. Front Microbiol 2024; 15:1451170. [PMID: 39600571 PMCID: PMC11590124 DOI: 10.3389/fmicb.2024.1451170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 08/27/2024] [Indexed: 11/29/2024] Open
Abstract
Primary liver cancer (PLC), comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), is a severe form of cancer associated with a high mortality and morbidity rate and increasing incidence worldwide. Current treatment options are limited and chemotherapeutics demonstrate strong side effects. New therapies are highly required. Lactobacilli represent the most diverse lactic acid-producing bacteria group and a prominent example of probiotics. Several studies have highlighted the anticancer efficacy of probiotics, especially of Lactiplantibacillus plantarum. However, there are limited studies on its activity on two PLC types, hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). This study evaluated the inhibitory mechanism and properties of L. plantarum ONU 12 (Lp 12) and L. plantarum ONU 355 (Lp 355), isolated from grapes in Ukraine and France, in murine PLC cell lines, in vitro. Strain Lacticaseibacillus casei ATCC 393 (Lc 393) has been taken for a direct comparison, as the most studied probiotic strain. The three Lactobacillus species were used in three forms: as live and heat-killed suspensions, and as sonicated extracts, and tested either as a monotherapy or in combination with standard chemotherapeutics (sorafenib for HCC and gemcitabine for CCA). Cell proliferation and viability were assessed via crystal violet staining assay and cell counting kit-8 assay. The induction of senescence was investigated by senescence-associated β-galactosidase assay. Fluorescence-activated cell sorting analysis was used to determine the apoptotic mechanism behind the inhibitory property of lactobacilli. The results showed that the live suspensions and sonicated extracts of Lp 12, Lp 355, and Lc 393 demonstrated inhibitory properties in CCA and HCC cells after 48 h of incubation. In combinations with standard chemotherapeutics, lactobacilli treatments have shown strong synergistic effects. The combination therapy allowed to reduce the chemotherapeutic doses of gemcitabine from 50 μM to 0.1 and 0.05 μM and sorafenib from 13.8 μM to 6.9 and 3.45 μM. Successful treatment regimes induced early apoptosis and cellular senescence in PLC, as the mechanism of inhibition. Heat-killed suspensions showed no inhibitory effect in none of the cell lines. Both strains, Lp 12 and Lp 355, showed successful results and need further testing in vivo, using autochthonous HCC and CCA models.
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Affiliation(s)
- Oladimeji Paul Duduyemi
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Kateryna Potapenko
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
- Department of Microbiology, Virology, and Biotechnology, Odesa I. I. Mechnykov National University, Odesa, Ukraine
| | - Nataliia Limanska
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
- Department of Microbiology, Virology, and Biotechnology, Odesa I. I. Mechnykov National University, Odesa, Ukraine
| | - Sofiya Kotsyuda
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Nataliia Petriv
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Huizhen Suo
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
| | - Tetyana Gudzenko
- Department of Microbiology, Virology, and Biotechnology, Odesa I. I. Mechnykov National University, Odesa, Ukraine
| | - Volodymyr Ivanytsia
- Department of Microbiology, Virology, and Biotechnology, Odesa I. I. Mechnykov National University, Odesa, Ukraine
| | - Tetyana Yevsa
- Department of Gastroenterology, Hepatology, Infectious Diseases, and Endocrinology, Hannover Medical School, Hanover, Germany
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Ma S, Meng G, Liu T, You J, He R, Zhao X, Cui Y. The Wnt signaling pathway in hepatocellular carcinoma: Regulatory mechanisms and therapeutic prospects. Biomed Pharmacother 2024; 180:117508. [PMID: 39362068 DOI: 10.1016/j.biopha.2024.117508] [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: 06/15/2024] [Revised: 08/26/2024] [Accepted: 09/25/2024] [Indexed: 10/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.
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Affiliation(s)
- Shihui Ma
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Guorui Meng
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Tong Liu
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Junqi You
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Risheng He
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Xudong Zhao
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Yunfu Cui
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China.
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Alnagar A, Zakeri N, Koilias K, Faulkes RE, Brown R, Cain O, Perera MTPR, Roberts KJ, Sanabria-Mateos R, Bartlett DC, Ma YT, Sivakumar S, Shetty S, Shah T, Dasari BVM. SIMAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation. World J Transplant 2024; 14:95849. [PMID: 39295983 PMCID: PMC11317860 DOI: 10.5500/wjt.v14.i3.95849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 05/28/2024] [Accepted: 07/01/2024] [Indexed: 07/31/2024] Open
Abstract
BACKGROUND Recurrence of hepatocellular carcinoma (HCC) following liver transplantation (LT) has a devastating influence on recipients' survival; however, the risk of recurrence is not routinely stratified. Risk stratification is vital with a long LT waiting time, as that could influence the recurrence despite strict listing criteria. AIM This study aims to identify predictors of recurrence and develop a novel risk prediction score to forecast HCC recurrence following LT. METHODS A retrospective review of LT for HCC recipients at University Hospitals Birmingham between July 2011 and February 2020. Univariate and multivariate analyses were performed to identify recurrence predictors, based on which the novel SIMAP500 (satellite nodules, increase in size, microvascular invasion, AFP > 500, poor differentiation) risk score was proposed. RESULTS 234 LTs for HCC were performed with a median follow-up of 5.3 years. Recurrence developed in 25 patients (10.7%). On univariate analyses, RETREAT score > 3, α-fetoprotein (AFP) at listing 100-500 and > 500, bridging, increased tumour size between imaging at the listing time and explant histology, increase in the size of viable tumour between listing and explant, presence of satellite nodules, micro- and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence, based on which, the SIMAP500 risk score is proposed. The SIMAP500 demonstrated an excellent predictive ability (c-index = 0.803) and outperformed the RETREAT score (c-index = 0.73). SIMAP500 is indicative of the time to disease recurrence. CONCLUSION SIMAP500 risk score identifies the LT recipients at risk of HCC recurrence. Risk stratification allows patient-centric post-transplant surveillance programs. Further validation of the score is recommended.
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Affiliation(s)
- Amr Alnagar
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Nekisa Zakeri
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Konstantinos Koilias
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rosemary E Faulkes
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rachel Brown
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - Owen Cain
- Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2GW, United Kingdom
| | - M Thamara P R Perera
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Keith J Roberts
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Rebeca Sanabria-Mateos
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - David C Bartlett
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Yuk Ting Ma
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shivan Sivakumar
- Department of Oncology, Queen Elizabeth Hospital, University Hospitals of Birmingham, Birmingham B15 2GW, United Kingdom
| | - Shishir Shetty
- Centre for Liver Research, Institute of Biomedical Research, Birmingham B15 2TT, United Kingdom
| | - Tahir Shah
- Department of Hepatology, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
| | - Bobby V M Dasari
- Department of HBP and Liver Transplantation Surgery, Queen Elizabeth Hospital, University Hospitals Birmingham, Birmingham B15 2GW, United Kingdom
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11
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Tologkos S, Papadatou V, Mitrakas AG, Pagonopoulou O, Tripsianis G, Alexiadis T, Alexiadi CA, Panagiotopoulos AP, Nikolaidou C, Lambropoulou M. An Immunohistochemical Study of MAGE Proteins in Hepatocellular Carcinoma. Diagnostics (Basel) 2024; 14:1692. [PMID: 39125568 PMCID: PMC11311968 DOI: 10.3390/diagnostics14151692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/22/2024] [Accepted: 07/26/2024] [Indexed: 08/12/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one the most common primary malignancies with high mortality and morbidity. The melanoma-associated antigen (MAGE) gene family includes several genes that are highly expressed in numerous human cancers, making many of them part of the cancer-testis antigen (CTA) family. MAGE-C1 is expressed in various malignancies but is absent in normal cells, except for the male germ line. Its presence is associated with a worse prognosis, increased tumor aggressiveness, and lymph node invasion. Similarly, MAGE-C2 is linked to the development of various malignant tumors. Despite these associations, the roles and mechanisms of MAGE-C1/MAGE-C2 in HCC remain unclear. This study aimed to evaluate the expression of MAGE-C1 and MAGE-C2 in HCC and correlate it with clinicohistological characteristics. Our findings indicated that MAGE-C1 expression is associated with a higher number of nodules, elevated AFP levels, HBV or HCV positivity, older age, male sex, and lymph node invasion. MAGE-C2 expression was correlated with these characteristics and the presence of cirrhosis. These results align with the limited literature, which suggests a correlation between MAGE expression and older age and HBV infection. Consequently, our study suggests that MAGE-C1 and MAGE-C2 are promising novel biomarkers for prognosis and potential therapeutic targets in HCC.
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Affiliation(s)
- Stylianos Tologkos
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Vasiliki Papadatou
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Achilleas G. Mitrakas
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Olga Pagonopoulou
- Laboratory of Neurophysiology, Medical School, Democritus University of Thrace, 68132 Alexandroupolis, Greece;
| | - Grigorios Tripsianis
- Laboratory of Medical Statistics, Medical School, Democritus University of Thrace, 68132 Alexandroupolis, Greece;
| | - Triantafyllos Alexiadis
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Christina-Angelika Alexiadi
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Antonios-Periklis Panagiotopoulos
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
| | - Christina Nikolaidou
- Laboratory of Pathology, Ippokrateio General Hospital of Thessaloniki, 54642 Thessaloniki, Greece;
| | - Maria Lambropoulou
- Laboratory of Histology-Embryology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece; (S.T.); (V.P.); (T.A.); (C.-A.A.); (A.-P.P.); (M.L.)
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12
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Suddle A, Reeves H, Hubner R, Marshall A, Rowe I, Tiniakos D, Hubscher S, Callaway M, Sharma D, See TC, Hawkins M, Ford-Dunn S, Selemani S, Meyer T. British Society of Gastroenterology guidelines for the management of hepatocellular carcinoma in adults. Gut 2024; 73:1235-1268. [PMID: 38627031 PMCID: PMC11287576 DOI: 10.1136/gutjnl-2023-331695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 03/19/2024] [Indexed: 05/01/2024]
Abstract
Deaths from the majority of cancers are falling globally, but the incidence and mortality from hepatocellular carcinoma (HCC) is increasing in the United Kingdom and in other Western countries. HCC is a highly fatal cancer, often diagnosed late, with an incidence to mortality ratio that approaches 1. Despite there being a number of treatment options, including those associated with good medium to long-term survival, 5-year survival from HCC in the UK remains below 20%. Sex, ethnicity and deprivation are important demographics for the incidence of, and/or survival from, HCC. These clinical practice guidelines will provide evidence-based advice for the assessment and management of patients with HCC. The clinical and scientific data underpinning the recommendations we make are summarised in detail. Much of the content will have broad relevance, but the treatment algorithms are based on therapies that are available in the UK and have regulatory approval for use in the National Health Service.
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Affiliation(s)
- Abid Suddle
- King's College Hospital NHS Foundation Trust, London, UK
| | - Helen Reeves
- Newcastle University Translational and Clinical Research Institute, Newcastle upon Tyne, UK
| | - Richard Hubner
- Department of Oncology, The Christie NHS Foundation Trust, Manchester, UK
| | | | - Ian Rowe
- University of Leeds, Leeds, UK
- St James's University Hospital, Leeds, UK
| | - Dina Tiniakos
- Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stefan Hubscher
- Department of Pathology, University of Birmingham, Birmingham, UK
| | - Mark Callaway
- Division of Diagnostics and Therapies, University Hospitals Bristol NHS Trust, Bristol, UK
| | | | - Teik Choon See
- Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Maria Hawkins
- Department of Medical Physics and Biomedical Engineering, University College London, London, UK
| | | | - Sarah Selemani
- King's College Hospital NHS Foundation Trust, London, UK
| | - Tim Meyer
- Department of Oncology, University College, London, UK
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13
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Huang XW, Li Y, Jiang LN, Zhao BK, Liu YS, Chen C, Zhao D, Zhang XL, Li ML, Jiang YY, Liu SH, Zhu L, Zhao JM. Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma. Transl Oncol 2024; 45:101986. [PMID: 38723299 PMCID: PMC11101742 DOI: 10.1016/j.tranon.2024.101986] [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: 10/17/2023] [Revised: 04/22/2024] [Accepted: 05/05/2024] [Indexed: 05/21/2024] Open
Abstract
Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.
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Affiliation(s)
- Xiao-Wen Huang
- Medical School of Chinese PLA, Beijing, China; Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yan Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li-Na Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Bo-Kang Zhao
- Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, China
| | - Yi-Si Liu
- First Department of Liver Disease Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Chun Chen
- Senior Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Dan Zhao
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Xue-Li Zhang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Mei-Ling Li
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Yi-Yun Jiang
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Shu-Hong Liu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Li Zhu
- Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Jing-Min Zhao
- Medical School of Chinese PLA, Beijing, China; Department of Pathology and Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.
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14
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Matsumoto T, Shiraki T, Niki M, Sato S, Tanaka G, Shimizu T, Yamaguchi T, Park KH, Mori S, Iso Y, Ishizuka M, Kubota K, Aoki T. Proposal of an integrated staging system using albumin-bilirubin grade and serum alpha-fetoprotein values for predicting postoperative prognosis of recurrent hepatocellular carcinoma. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2024; 50:108356. [PMID: 38685177 DOI: 10.1016/j.ejso.2024.108356] [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: 10/03/2023] [Revised: 03/26/2024] [Accepted: 04/18/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND Because repeat hepatectomy for recurrent hepatocellular carcinoma is a potentially invasive procedure, it is necessary to identify patients who truly benefit from repeat hepatectomy. Albumin-bilirubin grading has been reported to predict survival in patients with hepatocellular carcinoma. However, as prognosis also depends on tumor factors, a staging system that adds tumor factors to albumin-bilirubin grading may lead to a more accurate prognostication in patients with recurrent hepatocellular carcinoma. METHODS Albumin-bilirubin grading and serum alpha-fetoprotein levels were combined and the albumin-bilirubin-alpha-fetoprotein score was created ([albumin-bilirubin grading = 1; 1 point, 2 or 3; 2 points] + [alpha-fetoprotein<75 ng/mL, 0 points; ≥5, 1 point]). Patients were classified into three groups, and their characteristics and survival were evaluated. The predictive ability of the albumin-bilirubin-alpha-fetoprotein score was compared with that of the Cancer of the Liver Italian Program and the Japan Integrated Stage scores. RESULTS Albumin-bilirubin-alpha-fetoprotein score significantly stratified postoperative survival (albumin-bilirubin-alpha-fetoprotein score = 1/2/3: 5-year recurrence-free survival [%]: 22.4/20.7/0.0, p < 0.001) and showed the highest predictive value for survival among the integrated systems (albumin-bilirubin-alpha-fetoprotein score/Japan Integrated Stage/Cancer of the Liver Italian Program: 0.785/0.708/0.750). CONCLUSIONS Albumin-bilirubin-alpha-fetoprotein score is useful for predicting the survival of patients with recurrent hepatocellular carcinoma undergoing repeat hepatectomy.
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Affiliation(s)
- Takatsugu Matsumoto
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan.
| | - Takayuki Shiraki
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Maiko Niki
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Shun Sato
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Genki Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takayuki Shimizu
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takamune Yamaguchi
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Kyung-Hwa Park
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Shozo Mori
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Yukihiro Iso
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Mitsuru Ishizuka
- Department of Colorectal Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Keiichi Kubota
- Department of Surgery, Tohto Bunkyo Hospital, Tokyo, Japan
| | - Taku Aoki
- Department of Hepato-Biliary-Pancreatic Surgery, Dokkyo Medical University, Tochigi, Japan
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15
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Ali FEM, Ibrahim IM, Althagafy HS, Hassanein EHM. Role of immunotherapies and stem cell therapy in the management of liver cancer: A comprehensive review. Int Immunopharmacol 2024; 132:112011. [PMID: 38581991 DOI: 10.1016/j.intimp.2024.112011] [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: 02/02/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/08/2024]
Abstract
Liver cancer (LC) is the sixth most common disease and the third most common cause of cancer-related mortality. The WHO predicts that more than 1 million deaths will occur from LC by 2030. Hepatocellular carcinoma (HCC) is a common form of primary LC. Today, the management of LC involves multiple disciplines, and multimodal therapy is typically selected on an individual basis, considering the intricate interactions between the patient's overall health, the stage of the tumor, and the degree of underlying liver disease. Currently, the treatment of cancers, including LC, has undergone a paradigm shift in the last ten years because of immuno-oncology. To treat HCC, immune therapy approaches have been developed to enhance or cause the body's natural immune response to specifically target tumor cells. In this context, immune checkpoint pathway inhibitors, engineered cytokines, adoptive cell therapy, immune cells modified with chimeric antigen receptors, and therapeutic cancer vaccines have advanced to clinical trials and offered new hope to cancer patients. The outcomes of these treatments are encouraging. Additionally, treatment using stem cells is a new approach for restoring deteriorated tissues because of their strong differentiation potential and capacity to release cytokines that encourage cell division and the formation of blood vessels. Although there is no proof that stem cell therapy works for many types of cancer, preclinical research on stem cells has shown promise in treating HCC. This review provides a recent update regarding the impact of immunotherapy and stem cells in HCC and promising outcomes.
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Affiliation(s)
- Fares E M Ali
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt; Michael Sayegh, Faculty of Pharmacy, Aqaba University of Technology, Aqaba 77110, Jordan.
| | - Islam M Ibrahim
- Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, 71524, Egypt
| | - Hanan S Althagafy
- Department of Biochemistry, Faculty of Science, University of Jeddah, Jeddah, Saudi Arabia
| | - Emad H M Hassanein
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Assiut, 71524, Egypt
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16
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Jiang S, Gao X, Tian Y, Chen J, Wang Y, Jiang Y, He Y. The potential of 18F-FDG PET/CT metabolic parameter-based nomogram in predicting the microvascular invasion of hepatocellular carcinoma before liver transplantation. Abdom Radiol (NY) 2024; 49:1444-1455. [PMID: 38265452 DOI: 10.1007/s00261-023-04166-8] [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: 06/17/2023] [Revised: 06/17/2023] [Accepted: 12/16/2023] [Indexed: 01/25/2024]
Abstract
PURPOSE Microvascular invasion (MVI) is a critical factor in predicting the recurrence and prognosis of hepatocellular carcinoma (HCC) after liver transplantation (LT). However, there is a lack of reliable preoperative predictors for MVI. The purpose of this study is to evaluate the potential of an 18F-FDG PET/CT-based nomogram in predicting MVI before LT for HCC. METHODS 83 HCC patients who obtained 18F-FDG PET/CT before LT were included in this retrospective research. To determine the parameters connected to MVI and to create a nomogram for MVI prediction, respectively, Logistic and Cox regression models were applied. Analyses of the calibration curve and receiver operating characteristic (ROC) curves were used to assess the model's capability to differentiate between clinical factors and metabolic data from PET/CT images. RESULTS Among the 83 patients analyzed, 41% were diagnosed with histologic MVI. Multivariate logistic regression analysis revealed that Child-Pugh stage, alpha-fetoprotein, number of tumors, CT Dmax, and Tumor-to-normal liver uptake ratio (TLR) were significant predictors of MVI. A nomogram was constructed using these predictors, which demonstrated strong calibration with a close agreement between predicted and actual MVI probabilities. The nomogram also showed excellent differentiation with an AUC of 0.965 (95% CI 0.925-1.000). CONCLUSION The nomogram based on 18F-FDG PET/CT metabolic characteristics is a reliable preoperative imaging biomarker for predicting MVI in HCC patients before undergoing LT. It has demonstrated excellent efficacy and high clinical applicability.
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Affiliation(s)
- Shengpan Jiang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
- Department of Interventional Medicine, Wuhan Third Hospital (Tongren Hospital of Wuhan University), 216 Guanshan Avenue, Wuhan, 430074, China
| | - Xiaoqing Gao
- Clinical Laboratory Department, Wuhan Third Hospital (Tongren Hospital of Wuhan University), 216 Guanshan Avenue, Wuhan, 430074, China
| | - Yueli Tian
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Jie Chen
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yichun Wang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yaqun Jiang
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China
| | - Yong He
- Department of Nuclear Medicine, Zhongnan Hospital of Wuhan University, No. 169 Donghu Road, Wuchang District, Wuhan, 430071, China.
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17
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Llovet JM, Pinyol R, Yarchoan M, Singal AG, Marron TU, Schwartz M, Pikarsky E, Kudo M, Finn RS. Adjuvant and neoadjuvant immunotherapies in hepatocellular carcinoma. Nat Rev Clin Oncol 2024; 21:294-311. [PMID: 38424197 PMCID: PMC11984461 DOI: 10.1038/s41571-024-00868-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/02/2024] [Indexed: 03/02/2024]
Abstract
Liver cancer, specifically hepatocellular carcinoma (HCC), is the sixth most common cancer and the third leading cause of cancer mortality worldwide. The development of effective systemic therapies, particularly those involving immune-checkpoint inhibitors (ICIs), has substantially improved the outcomes of patients with advanced-stage HCC. Approximately 30% of patients are diagnosed with early stage disease and currently receive potentially curative therapies, such as resection, liver transplantation or local ablation, which result in median overall survival durations beyond 60 months. Nonetheless, up to 70% of these patients will have disease recurrence within 5 years of resection or local ablation. To date, the results of randomized clinical trials testing adjuvant therapy in patients with HCC have been negative. This major unmet need has been addressed with the IMbrave 050 trial, demonstrating a recurrence-free survival benefit in patients with a high risk of relapse after resection or local ablation who received adjuvant atezolizumab plus bevacizumab. In parallel, studies testing neoadjuvant ICIs alone or in combination in patients with early stage disease have also reported efficacy. In this Review, we provide a comprehensive overview of the current approaches to manage patients with early stage HCC. We also describe the tumour immune microenvironment and the mechanisms of action of ICIs and cancer vaccines in this setting. Finally, we summarize the available evidence from phase II/III trials of neoadjuvant and adjuvant approaches and discuss emerging clinical trials, identification of biomarkers and clinical trial design considerations for future studies.
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Affiliation(s)
- Josep M Llovet
- Liver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
- Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
| | - Roser Pinyol
- Liver Cancer Translational Research Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain
| | - Mark Yarchoan
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
- Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Amit G Singal
- Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Thomas U Marron
- Mount Sinai Liver Cancer Program, Divisions of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Myron Schwartz
- Department of Liver Surgery, Recanati/Miller Transplantation Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Eli Pikarsky
- The Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel-Canada (IMRIC), Hebrew University-Hadassah Medical School, Jerusalem, Israel
| | - Masatoshi Kudo
- Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan
| | - Richard S Finn
- Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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18
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Duan BT, Zhao XK, Cui YY, Liu DZ, Wang L, Zhou L, Zhang XY. Construction and validation of somatic mutation-derived long non-coding RNAs signatures of genomic instability to predict prognosis of hepatocellular carcinoma. World J Gastrointest Surg 2024; 16:842-859. [PMID: 38577085 PMCID: PMC10989333 DOI: 10.4240/wjgs.v16.i3.842] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2023] [Revised: 12/20/2023] [Accepted: 02/19/2024] [Indexed: 03/22/2024] Open
Abstract
BACKGROUND Long non-coding RNAs (LncRNAs) have been found to be a potential prognostic factor for cancers, including hepatocellular carcinoma (HCC). Some LncRNAs have been confirmed as potential indicators to quantify genomic instability (GI). Nevertheless, GI-LncRNAs remain largely unexplored. This study established a GI-derived LncRNA signature (GILncSig) that can predict the prognosis of HCC patients. AIM To establish a GILncSig that can predict the prognosis of HCC patients. METHODS Identification of GI-LncRNAs was conducted by combining LncRNA expression and somatic mutation profiles. The GI-LncRNAs were then analyzed for functional enrichment. The GILncSig was established in the training set by Cox regression analysis, and its predictive ability was verified in the testing set and TCGA set. In addition, we explored the effects of the GILncSig and TP53 on prognosis. RESULTS A total of 88 GI-LncRNAs were found, and functional enrichment analysis showed that their functions were mainly involved in small molecule metabolism and GI. The GILncSig was constructed by 5 LncRNAs (miR210HG, AC016735.1, AC116351.1, AC010643.1, LUCAT1). In the training set, the prognosis of high-risk patients was significantly worse than that of low-risk patients, and similar results were verified in the testing set and TCGA set. Multivariate Cox regression analysis and stratified analysis confirmed that the GILncSig could be used as an independent prognostic factor. Receiver operating characteristic curve analysis of the GILncSig showed that the area under the curve (0.773) was higher than the two LncRNA signatures published recently. Furthermore, the GILncSig may have a better predictive performance than TP53 mutation status alone. CONCLUSION We established a GILncSig that can predict the prognosis of HCC patients, which will help to guide prognostic evaluation and treatment decisions.
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Affiliation(s)
- Bo-Tao Duan
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Xue-Kai Zhao
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Yang-Yang Cui
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - De-Zheng Liu
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Lin Wang
- Department of Ophthalmology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Lei Zhou
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
| | - Xing-Yuan Zhang
- Department of Hepatobiliary Surgery, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
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Liu WM, Zhao XY, Gu MT, Song KR, Zheng W, Yu H, Chen HL, Xu XW, Zhou X, Liu AE, Jia NY, Wang PJ. Radiomics of Preoperative Multi-Sequence Magnetic Resonance Imaging Can Improve the Predictive Performance of Microvascular Invasion in Hepatocellular Carcinoma. World J Oncol 2024; 15:58-71. [PMID: 38274720 PMCID: PMC10807913 DOI: 10.14740/wjon1731] [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: 09/19/2023] [Accepted: 11/15/2023] [Indexed: 01/27/2024] Open
Abstract
Background The aim of the study is to demonstrate that radiomics of preoperative multi-sequence magnetic resonance imaging (MRI) can indeed improve the predictive performance of microvascular invasion (MVI) in hepatocellular carcinoma (HCC). Methods A total of 206 patients with pathologically confirmed HCC who underwent preoperative enhanced MRI were retrospectively recruited. Univariate and multivariate logistic regression analysis identified the independent clinicoradiologic predictors of MVI present and constituted the clinicoradiologic model. Recursive feature elimination (RFE) was applied to select radiomics features (extracted from six sequence images) and constructed the radiomics model. Clinicoradiologic model plus radiomics model formed the clinicoradiomics model. Five-fold cross-validation was used to validate the three models. Discrimination, calibration, and clinical utility were used to evaluate the performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to compare the prediction accuracy between models. Results The clinicoradiologic model contained alpha-fetoprotein (AFP)_lg10, radiological capsule enhancement, enhancement pattern and arterial peritumoral enhancement, which were independent risk factors of MVI. There were 18 radiomics features related to MVI constructed the radiomics model. The mean area under the receiver operating curve (AUC) of clinicoradiologic, radiomics and clinicoradiomics model were 0.849, 0.925 and 0.950 in the training cohort and 0.846, 0.907 and 0.933 in the validation cohort, respectively. The three models' calibration curves fitted well, and decision curve analysis (DCA) confirmed the clinical usefulness. Compared with the clinicoradiologic model, the NRI of radiomics and clinicoradiomics model increased significantly by 0.575 and 0.825, respectively, and the IDI increased significantly by 0.280 and 0.398, respectively. Conclusions Radiomics of preoperative multi-sequence MRI can improve the predictive performance of MVI in HCC.
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Affiliation(s)
- Wan Min Liu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- These authors contributed equally to this work
| | - Xing Yu Zhao
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- These authors contributed equally to this work
| | - Meng Ting Gu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Kai Rong Song
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Shanghai Naval Military Medical University, Shanghai, China
| | - Wei Zheng
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Shanghai Naval Military Medical University, Shanghai, China
| | - Hui Yu
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Shanghai Naval Military Medical University, Shanghai, China
| | - Hui Lin Chen
- School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai, China
| | - Xiao Wen Xu
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiang Zhou
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ai E Liu
- Department of Research Center, Shanghai United Imaging Intelligence Co., Ltd, Shanghai, China
| | - Ning Yang Jia
- Department of Radiology, Eastern Hepatobiliary Surgery Hospital, The Third Affiliated Hospital of Shanghai Naval Military Medical University, Shanghai, China
| | - Pei Jun Wang
- Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
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20
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Xiang C, Shen X, Zeng X, Zhang Y, Ma Z, Zhang G, Song X, Huang T, Yang J. Effect of transarterial chemoembolization as postoperative adjuvant therapy for intermediate-stage hepatocellular carcinoma with microvascular invasion: a multicenter cohort study. Int J Surg 2024; 110:315-323. [PMID: 37812183 PMCID: PMC10793739 DOI: 10.1097/js9.0000000000000805] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2023] [Accepted: 09/18/2023] [Indexed: 10/10/2023]
Abstract
BACKGROUND Intermediate-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI) is associated with high recurrence rates and poor survival outcomes after surgery. This study aimed to evaluate the efficacy of postoperative transarterial chemoembolization (TACE) on prognosis of intermediate-stage HCC patients with MVI after curative liver resection (LR). MATERIALS AND METHODS Patients who had intermediate-stage HCC with MVI and underwent curative LR between January 2013 and December 2019 at three institutions in China were identified for further analysis. Overall survival (OS) and recurrence-free survival (RFS) were compared between patients treated with and without postoperative TACE by propensity score-matching. RESULTS A total of 246 intermediate-stage HCC patients with MVI were enrolled, 137 entered into the LR group and 109 entered into the LR+TACE group. The 1-year, 3-year, and 5-year RFS rates were 42.0, 27.2, and 17.8% in LR+TACE group, and 31.8, 18.2, and 8.7% in LR group. The 1-year, 3-year, and 5-year OS rates were 81.7, 47.2, and 26.1% in the LR+TACE group, and 67.3, 35.6, and 18.5% in the LR group. Compared with LR alone, LR+TACE was associated with significantly better RFS [hazard ratio (HR), 1.443; 95% CI: 1.089-1.914; P =0.009] and OS (HR, 1.438; 95% CI: 1.049-1.972; P =0.023). No difference was observed with RFS and OS in single TACE and multiple TACE in the matched cohort. CONCLUSION Postoperative adjuvant TACE could be beneficial for intermediate-stage HCC patients with MVI.
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Affiliation(s)
| | - Xianbo Shen
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha
| | - Xinxin Zeng
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha
| | - Yuzhong Zhang
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha
| | - Zhongzhi Ma
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha
| | - Guocan Zhang
- Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University) Changsha
| | - Xin Song
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Jishou University, Jishou, Hunan province
| | - Tao Huang
- Department of Minimally Invasive Intervention, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou, Guangdong province, People’s Republic of China
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Park JW, Lee H, Hong H, Seong J. Efficacy of Radiomics in Predicting Oncologic Outcome of Liver-Directed Combined Radiotherapy in Locally Advanced Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:5405. [PMID: 38001665 PMCID: PMC10670316 DOI: 10.3390/cancers15225405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/05/2023] [Accepted: 11/10/2023] [Indexed: 11/26/2023] Open
Abstract
PURPOSE We investigated whether radiomic features extracted from three-phase dynamic contrast-enhanced computed tomography (CECT) can be used to predict clinical outcomes, including objective treatment response (OR) and in-field failure-free survival rate (IFFR), in patients with hepatocellular carcinoma (HCC) who received liver-directed combined radiotherapy (LD-CRT). METHODS We included 409 patients, and they were randomly divided into training (n = 307) and validation (n = 102) cohorts. For radiomics models, we extracted 116 radiomic features from the region of interest on the CECT images. Significant clinical prognostic factors are identified to predict the OR and IFFR in the clinical models. We developed clinical models, radiomics models, and a combination of both features (CCR model). RESULTS Among the radiomic models evaluated for OR, the OR-PVP-Peri-1cm model showed favorable predictive performance with an area under the curve (AUC) of 0.647. The clinical model showed an AUC of 0.729, whereas the CCR model showed better performance (AUC 0.759). For the IFFR, the IFFR-PVP-Peri-1cm model showed an AUC of 0.673, clinical model showed 0.687, and the CCR model showed 0.736. We also developed and validated a prognostic nomogram based on CCR models. CONCLUSION In predicting the OR and IFFR in patients with HCC undergoing LD-CRT, CCR models performed better than clinical and radiomics models. Moreover, the constructed nomograms based on these models may provide valuable information on the prognosis of these patients.
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Affiliation(s)
- Jong Won Park
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea;
| | - Hansang Lee
- School of Electrical Engineering, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea;
| | - Helen Hong
- Department of Software Convergence, College of Interdisciplinary Studies for Emerging Industries, 621 Hwarang-ro, Nowon-gu, Seoul 01797, Republic of Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea;
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22
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Tanaka T, Takata K, Miyayama T, Shibata K, Fukuda H, Yamauchi R, Fukunaga A, Yokoyama K, Shakado S, Sakisaka S, Hirai F. Long-term outcome and eligibility of radiofrequency ablation for hepatocellular carcinoma over 3.0 cm in diameter. Sci Rep 2023; 13:16286. [PMID: 37770523 PMCID: PMC10539460 DOI: 10.1038/s41598-023-43516-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 09/25/2023] [Indexed: 09/30/2023] Open
Abstract
Percutaneous radiofrequency ablation (RFA) is effective for the treatment of small hepatocellular carcinoma (HCC) with a diameter ≤ 3.0 cm. The present study aimed to elucidate the prognostic factors and clarify the indication of treatment for RFA outcomes in patients with HCC with a diameter > 3.0 cm. Among 2188 patients with HCC who underwent RFA, 100 patients with HCC with a diameter > 3.0 cm were enrolled in this study between August, 2000 and August, 2021. We analyzed local therapeutic efficacy, long-term outcomes, and prognostic factors in patients with HCC with a diameter > 3.0 cm. Among all patients, 77 patients achieved complete ablation in one session. There were no treatment-related deaths or major complications. Local tumor recurrence occurred in 48% (n = 48) of the patients, and distant tumor recurrence occurred in 82% (n = 82) of the patients during the study period. The survival rates at 1-, 3-, 5-, 10-, and 15- years were 93.0%, 66.0%, 40.0%, 15.5%, and 10.2%, respectively. Cox proportional hazards regression analysis confirmed that distant tumor recurrence, Child-Pugh class B, and pre-ablation des-γ-carboxy prothrombin (DCP) levels ≥ 200 mAU/mL were independent unfavorable prognostic factors with a hazard ratio of 3.34 (95% CI, 1.57-7.11; P = 0.002), 2.43 (95% CI, 1.35-4.37; P = 0.003), and 1.83 (95% CI, 1.14-2.93; P = 0.012), respectively. In conclusion, patients with HCC with a diameter > 3.0 cm with Child-Pugh class A and DCP levels < 200 mAU/mL might be eligible for RFA treatment.
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Affiliation(s)
- Takashi Tanaka
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan.
| | - Kazuhide Takata
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Takashi Miyayama
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Kumiko Shibata
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Hiromi Fukuda
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Ryo Yamauchi
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Atsushi Fukunaga
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Keiji Yokoyama
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Satoshi Shakado
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
| | - Fumihito Hirai
- Department of Gastroenterology and Medicine, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Jonan-Ku, Fukuoka, 814-0180, Japan
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23
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Mo A, Lin B, Chen D. Efficacy of sequential TACE on primary hepatocellular carcinoma with microvascular invasion after radical resection: a systematic review and meta-analysis. World J Surg Oncol 2023; 21:277. [PMID: 37667375 PMCID: PMC10478229 DOI: 10.1186/s12957-023-03160-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 08/24/2023] [Indexed: 09/06/2023] Open
Abstract
OBJECTIVES The purpose of this study is to examine the impact of sequential transcatheter arterial chemoembolization (TACE) on the prognosis of patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) following radical resection. METHODS Five databases were searched for studies on the efficacy of TACE after radical hepatectomy resection (HR) for treating HCC with MVI. Depending on the heterogeneity between included studies, the relative risk (RR) and 95% confidence interval (CI) were computed using a random or fixed effect model. RESULTS Thirteen articles were included in this study. There were 1378 cases in the HR-TACE group (cases undergoing TACE after HR) and 1636 cases in the HR group (cases only undergoing HR). The recurrence-free survival (RFS) at 1 year, 2 years, 3 years, and 5 years after radical HCC resection was statistically significantly greater in the HR-TACE group than in the HR group. The HR-TACE group exhibited statistically significant advantages at 1-year, 2-year, 3-year, and 5-year overall survival (OS) after radical HCC resection when compared with the HR group. CONCLUSION Postoperative sequential TACE treatment can improve the RFS and OS rates at 1 year, 2 years, 3 years, and 5 years following radical HR in patients with HCC and MVI. These findings will guide clinicians in selecting appropriate cases for adjuvant TACE treatment during clinical diagnosis and treatment to maximize patient benefit. TRIAL REGISTRATION PROSPERO CRD42023449238.
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Affiliation(s)
- Anwei Mo
- Department of Medical Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
| | - Biquan Lin
- Intervention Clinic, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19 Xiuhua Road, Haikou, Hainan, 570000, China.
| | - Denglin Chen
- Department of Medical Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China
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Lorton O, Guillemin PC, Peloso A, M’Rad Y, Crowe LA, Koessler T, Poletti PA, Boudabbous S, Ricoeur A, Salomir R. In Vivo Thermal Ablation of Deep Intrahepatic Targets Using a Super-Convergent MRgHIFU Applicator and a Pseudo-Tumor Model. Cancers (Basel) 2023; 15:3961. [PMID: 37568777 PMCID: PMC10417404 DOI: 10.3390/cancers15153961] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 07/28/2023] [Accepted: 08/01/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND HIFU ablation of liver malignancies is particularly challenging due to respiratory motion, high tissue perfusion and the presence of the rib cage. Based on our previous development of a super-convergent phased-array transducer, we aimed to further investigate, in vivo, its applicability to deep intrahepatic targets. METHODS In a series of six pigs, a pseudo-tumor model was used as target, visible both on intra-operatory MRI and post-mortem gross pathology. The transcostal MRgHIFU ablation was prescribed coplanar with the pseudo-tumor, either axial or sagittal, but deliberately shifted 7 to 18 mm to the side. No specific means of protection of the ribs were implemented. Post-treatment MRI follow-up was performed at D7, followed by animal necropsy and gross pathology of the liver. RESULTS The pseudo-tumor was clearly identified on T1w MR imaging and subsequently allowed the MRgHIFU planning. The peak temperature at the focal point ranged from 58-87 °C. Gross pathology confirmed the presence of the pseudo-tumor and the well-delineated MRgHIFU ablation at the expected locations. CONCLUSIONS The specific design of the transducer enabled a reliable workflow. It demonstrated a good safety profile for in vivo transcostal MRgHIFU ablation of deep-liver targets, graded as challenging for standard surgery.
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Affiliation(s)
- Orane Lorton
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | - Pauline Coralie Guillemin
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | - Andrea Peloso
- Visceral Surgery Division, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Yacine M’Rad
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
| | | | - Thibaud Koessler
- Oncology Department, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | | | - Sana Boudabbous
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
- Radiology Division, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Alexis Ricoeur
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
- Radiology Division, University Hospitals of Geneva, 1205 Geneva, Switzerland
| | - Rares Salomir
- Image Guided Interventions Laboratory (GR-949), Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland
- Radiology Division, University Hospitals of Geneva, 1205 Geneva, Switzerland
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Kim J, Hong SK, Kim JY, Lee J, Choi HH, Lee S, Hong SY, Lee JM, Choi Y, Yi NJ, Lee KW, Suh KS. Recurrence in patients with totally necrotic nodules of hepatocellular carcinoma after liver transplantation: "totally" an inaccurate description. Ann Surg Treat Res 2023; 105:47-56. [PMID: 37441322 PMCID: PMC10333804 DOI: 10.4174/astr.2023.105.1.47] [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: 02/22/2023] [Revised: 06/04/2023] [Accepted: 06/08/2023] [Indexed: 07/15/2023] Open
Abstract
Purpose Total necrosis of hepatocellular carcinoma (HCC) achieved via locoregional treatment (LRT) is considered to indicate a lack of tumor viability. Nonetheless, there is insufficient evidence of recurrence after liver transplantation (LT) in patients with such a status. The aim of this study was to investigate the prognosis of patients diagnosed with totally necrotic nodules upon explant hepatectomy after LT. Methods We conducted a retrospective study of patients diagnosed with totally necrotic nodules after LT for HCC. A total of 165 patients with HCC who underwent living- or deceased-donor LT from 2000 to 2020 in our hospital were included. Results A total of 5 patients (3.0%) exhibited HCC recurrence during a median follow-up of 84 months (range, 4-243 months) after LT. The 5-year overall and recurrence-free survival rates of these patients were 92.8% and 92.2%, respectively. Four patients in the HCC-recurrence group (80.0%) died even after further treatment, including transarterial chemoembolization, surgery, and systemic treatment. Both univariate and multivariate analyses of clinicopathological factors identified a maximum diameter of the totally necrotic nodules of >5 cm as the only factor associated with tumor recurrence following LT (P = 0.005 and P = 0.009, respectively). Conclusion Total necrosis of HCC via LRT yielded excellent survival outcomes for patients undergoing LT. Nevertheless, patients with large tumors should be considered at high risk of recurrence after LT, suggesting the need for their active surveillance during the follow-up period.
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Affiliation(s)
- Jiyoung Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Suk Kyun Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jae-Yoon Kim
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jaewon Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Hwa Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Sola Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Su young Hong
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Moo Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - YoungRok Choi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Nam-Joon Yi
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kwang-Woong Lee
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
| | - Kyung-Suk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Korea
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Yang L, Jia X, Fu Y, Tian J, Liu Y, Lin J. Creation of a Prognostic Model Using Cuproptosis-Associated Long Noncoding RNAs in Hepatocellular Carcinoma. Int J Mol Sci 2023; 24:9987. [PMID: 37373132 DOI: 10.3390/ijms24129987] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 06/03/2023] [Accepted: 06/06/2023] [Indexed: 06/29/2023] Open
Abstract
Cuproptosis is an unusual form of cell death caused by copper accumulation in mitochondria. Cuproptosis is associated with hepatocellular carcinoma (HCC). Long noncoding RNAs (LncRNAs) have been shown to be effective prognostic biomarkers, yet the link between lncRNAs and cuproptosis remains unclear. We aimed to build a prognostic model of lncRNA risk and explore potential biomarkers of cuproptosis in HCC. Pearson correlations were used to derive lncRNAs co-expressed in cuproptosis. The model was constructed using Cox, Lasso, and multivariate Cox regressions. Kaplan-Meier survival analysis, principal components analysis, receiver operating characteristic curve, and nomogram analyses were carried out for validation. Seven lncRNAs were identified as prognostic factors. A risk model was an independent prognostic predictor. Among these seven lncRNAs, prostate cancer associated transcript 6 (PCAT6) is highly expressed in different types of cancer, activating Wnt, PI3K/Akt/mTOR, and other pathways; therefore, we performed further functional validation of PCAT6 in HCC. Reverse transcription-polymerase chain reaction results showed that PCAT6 was aberrantly highly expressed in HCC cell lines (HepG2 and Hep3B) compared to LO2 (normal hepatocytes). When its expression was knocked down, cells proliferated and migrated less. PCAT6 might be a potential biomarker for predicting prognosis in HCC.
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Affiliation(s)
- Lihong Yang
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
| | - Xiao Jia
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
| | - Yueyue Fu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
| | - Jiao Tian
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
| | - Yijin Liu
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
| | - Jianping Lin
- State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300000, China
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Tang YL, Tao Y, Zhu L, Shen JL, Cheng H. Role of NLRP3 inflammasome in hepatocellular carcinoma: A double-edged sword. Int Immunopharmacol 2023; 118:110107. [PMID: 37028274 DOI: 10.1016/j.intimp.2023.110107] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/02/2023] [Accepted: 03/24/2023] [Indexed: 04/09/2023]
Abstract
In recent years, the study of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has become a hot topic, especially its role in various tumors. The incidence of hepatocellular carcinoma is ranked in the top five in China. Hepatocellular carcinoma (HCC) is the predominant and typical form of primary liver cancer. Due to the close relationship between NLRP3 inflammasome and cancers, many studies have investigated its role in HCC. The results suggest that NLRP3 inflammasome participates in both tumor growth inhibition and tumor growth promotion in HCC. Therefore, this review elaborates on the relationship between NLRP3 and HCC and explains its role in HCC. In addition, the potential of NLRP3 as a therapeutic target for cancer therapy is explored, summarizing and classifying impacts of and processes underlying different NLRP3 inflammasome-targeting drugs on HCC.
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Affiliation(s)
- Ying-Le Tang
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Yan Tao
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Lin Zhu
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Jia-Lin Shen
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China
| | - Hong Cheng
- Medical College, Yangzhou University, Yangzhou, China; Yangzhou University Medical College, Jiangsu Key Laboratory of Experimental & Translational Non-coding RNA Research, Institute of Translational Medicine, Yangzhou University, Jiangsu, Yangzhou, China.
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Mete D, Yemeztaşlıca E, Şanlı-Mohamed G. Sorafenib loaded ZIF-8 metal-organic frameworks as a multifunctional nano-carrier offers effective hepatocellular carcinoma therapy. J Drug Deliv Sci Technol 2023. [DOI: 10.1016/j.jddst.2023.104362] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/17/2023]
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Novel Gene Signatures Promote Epithelial-Mesenchymal Transition (EMT) in Glucose Deprivation-Based Microenvironment to Predict Recurrence-Free Survival in Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2023; 2023:6114976. [PMID: 36866237 PMCID: PMC9974289 DOI: 10.1155/2023/6114976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 01/28/2023] [Accepted: 02/02/2023] [Indexed: 02/24/2023]
Abstract
Background Current research studies have suggested that glucose deprivation (GD)-based tumor microenvironment (TME) can promote epithelial-mesenchymal transition (EMT) of tumor cells, leading to tumor invasion and metastasis. However, no one has yet studied detailedly the synthetic studies that include GD features in TME with EMT status. In our research, we comprehensively developed and validated a robust signature regarding GD and EMT status to provide prognostic value for patients with liver cancer. Methods GD and EMT status were estimated with transcriptomic profiles based on WGCNA and t-SNE algorithms. Two cohorts of training (TCGA_LIHC) and validation (GSE76427) datasets were analyzed with the Cox regression and logistic regression analyses. We identified a 2-mRNA signature to establish a GD-EMT-based gene risk model for the prediction of HCC relapse. Results Patients with significant GD-EMT status were divided into two subgroups: GDlow/EMTlow and GDhigh/EMThigh, with the latter having significantly worse recurrence-free survival (P < 0.01). We employed the least absolute shrinkage and selection operator (LASSO) technique as a method for HNF4A and SLC2A4 filtering and constructing a risk score for risk stratification. In the multivariate analysis, this risk score predicted recurrence-free survival (RFS) in both the discovery and validation cohorts and remained valid in patients stratified by TNM stage and age at diagnosis. The nomogram that combines risk score and TNM stage as well as age produces improved performance and net benefits in the analysis of calibration and decision curves in training and validation groups. Conclusions The GD-EMT-based signature predictive model may provide a prognosis classifier for HCC patients with a high risk of postoperative recurrence to decrease the relapse rate.
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Rossotti R, Merli M, Mazzarelli C, De Carlis RM, Travi G, Vecchi M, Viganò R, Lauterio A, Raimondi A, Belli LS, De Carlis LG, Puoti M. Similar survival but higher and delayed hepatocellular carcinoma recurrence in HIV-positive compared to negative cirrhotics undergoing liver transplantation. Dig Liver Dis 2023; 55:268-275. [PMID: 35644890 DOI: 10.1016/j.dld.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2021] [Revised: 05/04/2022] [Accepted: 05/05/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. AIMS To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. METHODS Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. RESULTS Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p = 0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p = 0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p = 0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p < 0.001). CONCLUSIONS Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.
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Affiliation(s)
- Roberto Rossotti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
| | - Marco Merli
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Chiara Mazzarelli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Riccardo Maria De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Giovanna Travi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Marta Vecchi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Raffaella Viganò
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Andrea Lauterio
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Alessandro Raimondi
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luca Saverio Belli
- Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy
| | - Luciano Gregorio De Carlis
- Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
| | - Massimo Puoti
- Department of Infectious Diseases, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Hepatology and Gastroenterology Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of General Surgery and Transplantation, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; School of Medicine, University of Milan-Bicocca, Milan, Italy
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31
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Oh S, Jo S, Kim HS, Mai VH, Endaya B, Neuzil J, Jung KH, Hong SS, Kim JM, Park S. Chemical Biopsy for GNMT as Noninvasive and Tumorigenesis-Relevant Diagnosis of Liver Cancer. Anal Chem 2023; 95:1184-1192. [PMID: 36602057 DOI: 10.1021/acs.analchem.2c03944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Early diagnosis of hepatocellular carcinoma (HCC) is difficult; the lack of convenient biomarker-based diagnostic modalities renders high-risk HCC patients burdened by life-long periodical examinations. Here, a new chemical biopsy approach was developed for noninvasive diagnosis of HCC using urine samples. Bioinformatic screening for tumor suppressors yielded glycine N-methyltransferase (GNMT) as a biomarker with clinical relevance to HCC tumorigenesis. A liquid chromatography-mass spectrometry (LC-MS)-based chemical biopsy detecting nonradioactive 13C-sarcosine from 13C-glycine was designed to noninvasively assess liver GNMT activity extrahepatically. 13C-Sarcosine showed a strong correlation with GNMT in normal and cancerous liver cells. In an autochthonous animal model developing visible cancer nodules at 17 weeks, the urinary 13C-sarcosine chemical biopsy exhibited notable changes as early as 8 weeks, showing significant correlations with liver GNMT and molecular pathological changes. Our chemical biopsy approach should facilitate early and noninvasive diagnosis of HCC, with direct relevance to tumorigenesis, which can be straightforwardly applied to other diseases.
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Affiliation(s)
- Sehyun Oh
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
| | - Sihyang Jo
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
| | - Han Sun Kim
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
| | - Van-Hieu Mai
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
| | - Berwini Endaya
- School of Pharmacy and Medical Science, Griffith University, Southport 4222, Qld, Australia
| | - Jiri Neuzil
- School of Pharmacy and Medical Science, Griffith University, Southport 4222, Qld, Australia.,Institute of Biotechnology, Czech Academy of Sciences, Prague-West 252 50, Czech Republic.,Faculty of Science, Charles University, Prague 128 00, Czech Republic
| | - Kyung Hee Jung
- Department of Biomedical Sciences, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 22332, Korea
| | - Soon-Sun Hong
- Department of Biomedical Sciences, College of Medicine, Inha University, 3-ga, Sinheung-dong, Jung-gu, Incheon 22332, Korea
| | - Jin-Mo Kim
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
| | - Sunghyouk Park
- College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul 08826, Korea
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Sharma A, Sharma L, Nandy SK, Payal N, Yadav S, Vargas-De-La-Cruz C, Anwer MK, Khan H, Behl T, Bungau SG. Molecular Aspects and Therapeutic Implications of Herbal Compounds Targeting Different Types of Cancer. Molecules 2023; 28:750. [PMID: 36677808 PMCID: PMC9867434 DOI: 10.3390/molecules28020750] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/05/2023] [Accepted: 01/08/2023] [Indexed: 01/15/2023] Open
Abstract
Due to genetic changes in DNA (deoxyribonucleic acid) sequences, cancer continues to be the second most prevalent cause of death. The traditional target-directed approach, which is confronted with the importance of target function in healthy cells, is one of the most significant challenges in anticancer research. Another problem with cancer cells is that they experience various mutations, changes in gene duplication, and chromosomal abnormalities, all of which have a direct influence on the potency of anticancer drugs at different developmental stages. All of these factors combine to make cancer medication development difficult, with low clinical licensure success rates when compared to other therapy categories. The current review focuses on the pathophysiology and molecular aspects of common cancer types. Currently, the available chemotherapeutic drugs, also known as combination chemotherapy, are associated with numerous adverse effects, resulting in the search for herbal-based alternatives that attenuate resistance due to cancer therapy and exert chemo-protective actions. To provide new insights, this review updated the list of key compounds that may enhance the efficacy of cancer treatment.
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Affiliation(s)
- Aditi Sharma
- Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, Himachal Pradesh, India
| | - Lalit Sharma
- Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, Himachal Pradesh, India
| | - Shouvik Kumar Nandy
- Department of Pharmacology, School of Pharmaceutical Sciences, Shoolini University, Solan 173229, Himachal Pradesh, India
| | - Nazrana Payal
- School of Biotechnology, Shoolini University of Biotechnology and Management Sciences, Solan 173229, Himachal Pradesh, India
| | - Shivam Yadav
- Department of Pharmaceutical Sciences, School of Pharmaceutical Sciences, Chhatrapati Shahu ji Maharaj University, Kanpur 208024, Uttar Pradesh, India
| | - Celia Vargas-De-La-Cruz
- Department of Pharmacology, Faculty of Pharmacy and Biochemistry, Bromatology and Toxicology, Universidad Nacional Mayor de San Marcos, Lima 150001, Peru
- E-Health Research Center, Universidad de Ciencias y Humanidades, Lima 15001, Peru
| | - Md. Khalid Anwer
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Haroon Khan
- Department of Pharmacy, Abdul Wali Khan University, Mardan 23200, Pakistan
| | - Tapan Behl
- School of Health Science and Technology, University of Petroleum and Energy Studies, Dehradun 248007, Uttarakhand, India
| | - Simona Gabriela Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
- Doctoral School of Biomedical Sciences, University of Oradea, 410028 Oradea, Romania
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Hu J, Gong N, Li D, Deng Y, Chen J, Luo D, Zhou W, Xu K. Identifying hepatocellular carcinoma patients with survival benefits from surgery combined with chemotherapy: based on machine learning model. World J Surg Oncol 2022; 20:377. [PMID: 36451200 PMCID: PMC9714169 DOI: 10.1186/s12957-022-02837-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/03/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is still fatal even after surgical resection. The purpose of this study was to analyze the prognostic factors of 5-year survival rate and to establish a model to identify HCC patients with gain of surgery combined with chemotherapy. METHODS All patients with HCC after surgery from January 2010 to December 2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic analysis were used to analyze the prognostic factors of patients, and the risk prediction model of 5-year survival rate of HCC patients was established by classical decision tree method. Propensity score matching was used to eliminate the confounding factors of whether to receive chemotherapy in high-risk group or low-risk group. RESULTS One-thousand six-hundred twenty-five eligible HCC patients were included in the study. Marital status, α-fetoprotein (AFP), vascular infiltration, tumor size, number of lesions, and grade were independent prognostic factors affecting the 5-year survival rate of HCC patients. The area under the curve of the 5-year survival risk prediction model constructed from the above variables was 0.76, and the classification accuracy, precision, recall, and F1 scores were 0.752, 0.83, 0.842, and 0.836, respectively. High-risk patients classified according to the prediction model had better 5-year survival rate after chemotherapy, while there was no difference in 5-year survival rate between patients receiving chemotherapy and patients not receiving chemotherapy in the low-risk group. CONCLUSIONS The 5-year survival risk prediction model constructed in this study provides accurate survival prediction information. The high-risk patients determined according to the prediction model may benefit from the 5-year survival rate after combined chemotherapy.
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Affiliation(s)
- Jie Hu
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Ni Gong
- Department of Nursing, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Dan Li
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China
| | - Youyuan Deng
- Department of General Surgery, The Central Hospital of Xiangtan City, Xiangtan, Hunan, China
| | - Jiawei Chen
- Department of Rehabilitation, The Central Hospital of Xiangtan City, Xiangtan, Hunan, China
| | - Dingan Luo
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
| | - Wei Zhou
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China.
- Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
| | - Ke Xu
- Clinical Medical College, Chengdu Medical College, Chengdu, Sichuan, China.
- Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan, China.
- Key Clinical Specialty of Sichuan Province, Chengdu, Sichuan, China.
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Yang WL, Zhu F, Chen WX. Texture analysis of contrast-enhanced magnetic resonance imaging predicts microvascular invasion in hepatocellular carcinoma. Eur J Radiol 2022; 156:110528. [PMID: 36162156 DOI: 10.1016/j.ejrad.2022.110528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 04/03/2022] [Accepted: 09/15/2022] [Indexed: 11/03/2022]
Abstract
BACKGROUND Microvascular invasion is one of the important risk factors of postoperative recurrence of hepatocellular carcinoma. Texture analysis uses mathematical methods to analyze the gray's quantitative value and distribution of images, for quantifying the heterogeneity of tissues. PURPOSE To investigate the feasibility of predicting MVI in HCC by analyzing the texture features of hepatic MR-enhanced images. METHODS 110 patients with HCC who underwent MR-enhanced examinations were included in this study, were divided into MVI-positive group (n = 52) and MVI-negative group (n = 58) according to postoperative pathology. Clinical, pathological data and MR imaging features were collected. 11 texture parameters were selected from the gray histogram and gray level co-occurrence matrix (GLCM). Texture parameters of MR-enhanced images were calculated for statistical analysis. RESULTS There were statistically significant differences in tumor size, location, degree of differentiation, AFP level, signal, pseudocapsule, margin, peritumoral enhancement and intratumoral artery between MVI-positive group and MVI-negative group (P < 0.05). The AUC value of combining MR image features in prediction of MVI was 0.693(sensitivity and specificity: 53.8 %, 82.8 %, respectively). There were statistically significant differences in the texture parameters of GLCM between two groups (P < 0.05). The AUC value of combining texture parameters in prediction of MVI was 0.797 (sensitivity and specificity: 88.2 %, 62.7 %, respectively). CONCLUSION MR image features and texture analysis have certain predictive effect on MVI, which are mutually verified and complementary. The texture parameters of GLCM could reflect tumor heterogeneity, which have great potential to help with preoperative decision. The combination of MR image features and texture analysis may improve the efficiency in prediction of MVI.
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Affiliation(s)
- Wei-Lin Yang
- Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China
| | - Fei Zhu
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041, PR China
| | - Wei-Xia Chen
- Department of Radiology, West China Hospital, Sichuan University, 37# Guo Xue Xiang, Chengdu, Sichuan 610041, PR China.
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Huang L, Li L, Cheng B, Xing T. SLC38A6, regulated by EP300-mediated modifications of H3K27ac, promotes cell proliferation, glutamine metabolism and mitochondrial respiration in hepatocellular carcinoma. Carcinogenesis 2022; 43:885-894. [PMID: 35901507 DOI: 10.1093/carcin/bgac061] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2022] [Revised: 07/08/2022] [Accepted: 07/25/2022] [Indexed: 02/05/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common form of liver cancer. The incidence of HCC is increasing and effective prevention methods are needed. The solute carrier family 38 member 6 (SLC38A6) plays an important role in the metabolism of glutamine, which is a central nutrient for many cancers. However, the regulation and function of SLC38A6 in HCC are unclear. SLC38A6 levels in human HCC tissue arrays and cells were determined. SLC38A6 was silenced or overexpressed to determine its role in regulating cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration. A luminescence assay was used to study the interaction between SLC38A6 and EP300. The interactions between SLC38A6, H3K27ac and EP300 were determined using chromatin immunoprecipitation assays. Quantitative RT-PCR and immunoblots were performed to measure mRNAs and proteins, respectively. SLC38A6 expression was higher in HCC compared with expression in normal tissue. Silencing SLC38A6 inhibited cell viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration, while SLC38A6 overexpression had the opposite effects. Silencing SLC38A6 also inhibited tumor growth in vivo. Silencing EP300 significantly suppressed the interaction between H3K27ac and the SLC38A6 promoter, leading to decreased SLC38A6. SLC38A6 is regulated by EP300-mediated modifications of H3K27ac and promotes viability, colony formation, cell cycle progression, glutamine metabolism and mitochondrial respiration in HCC cells.
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Affiliation(s)
- Li Huang
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Lixing Li
- Department of General Surgery, Shanghai Xuhui District Central Hospital, Shanghai, China
| | - Bin Cheng
- Department of Nuclear Medicine, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Tonghai Xing
- Department of General Surgery, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Zhang KJ, Ye TW, Lu WF, Xu FQ, Xie YM, Wang DD, Xiao ZQ, Liu SY, Yao WF, Cheng J, Shen GL, Liu JW, Zhang CW, Huang DS, Liang L. Impact of metabolic syndrome on the long-term prognosis of patients with hepatitis B virus-related hepatocellular carcinoma after hepatectomy. Front Oncol 2022; 12:1042869. [PMID: 36338761 PMCID: PMC9632286 DOI: 10.3389/fonc.2022.1042869] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Accepted: 10/07/2022] [Indexed: 11/16/2022] Open
Abstract
Background & aims The long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy. Methods Patients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Result 389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002). Conclusion MS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.
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Affiliation(s)
- Kang-Jun Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Tai-Wei Ye
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Wen-Feng Lu
- Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, China
| | - Fei-Qi Xu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- The Second School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, China
| | - Ya-Ming Xie
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong-Dong Wang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Zun-Qiang Xiao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Si-Yu Liu
- Department of Medical, Lishui Municipal Central Hospital, Lishui, Zhejiang, China
| | - Wei-Feng Yao
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jian Cheng
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Guo-Liang Shen
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Jun-Wei Liu
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Cheng-Wu Zhang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Dong-Sheng Huang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China
- Department of Clinical Medicine, Hangzhou Medical College, Hangzhou, Zhejiang, China
- *Correspondence: Lei Liang, ; Dong-Sheng Huang,
| | - Lei Liang
- General Surgery, Department of Hepatobiliary and Pancreatic Surgery and Minimal Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, China
- *Correspondence: Lei Liang, ; Dong-Sheng Huang,
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Wang SY, Huang YH, Liang YJ, Wu JC. Gene coexpression network analysis identifies hubs in hepatitis B virus-associated hepatocellular carcinoma. J Chin Med Assoc 2022; 85:972-980. [PMID: 35801949 DOI: 10.1097/jcma.0000000000000772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. The molecular pathogenesis of HCC involves multiple signaling pathways. This study utilizes systems and bioinformatic approaches to investigate the pathogenesis of HCC. METHODS Gene expression microarray data were obtained from 50 patients with chronic hepatitis B and HCC. There were 1649 differentially expressed genes inferred from tumorous and nontumorous datasets. Weighted gene coexpression network analysis (WGCNA) was performed to construct clustered coexpressed gene modules. Statistical analysis was used to study the correlation between gene coexpression networks and demographic features of patients. Functional annotation and pathway inference were explored for each coexpression network. Network analysis identified hub genes of the prognostic gene coexpression network. The hub genes were further validated with a public database. RESULT Five distinct gene coexpression networks were identified by WGCNA. A distinct coexpressed gene network was significantly correlated with HCC prognosis. Pathway analysis of this network revealed extensive integration with cell cycle regulation. Ten hub genes of this gene network were inferred from protein-protein interaction network analysis and further validated in an external validation dataset. Survival analysis showed that lower expression of the 10-gene signature had better overall survival and recurrence-free survival. CONCLUSION This study identified a crucial gene coexpression network associated with the prognosis of hepatitis B virus-related HCC. The identified hub genes may provide insights for HCC pathogenesis and may be potential prognostic markers or therapeutic targets.
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Affiliation(s)
- Shen-Yung Wang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Department of Medicine, MacKay Memorial Hospital, Taipei, Taiwan, ROC
| | - Yen-Hua Huang
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Center for Systems and Synthetic Biology, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
| | - Yuh-Jin Liang
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC
- Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
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Li W, Shen H, Han L, Liu J, Xiao B, Li X, Ye Z. A Multiparametric Fusion Radiomics Signature Based on Contrast-Enhanced MRI for Predicting Early Recurrence of Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:3704987. [PMID: 36213823 PMCID: PMC9534653 DOI: 10.1155/2022/3704987] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Accepted: 07/28/2022] [Indexed: 11/18/2022]
Abstract
Objectives The postoperative early recurrence (ER) rate of hepatocellular carcinoma (HCC) is 50%, and no highly reliable predictive tool has been developed yet. The aim of this study was to develop and validate a predictive model with radiomics analysis based on multiparametric magnetic resonance (MR) images to predict early recurrence of HCC. Methods In total, 302 patients (training dataset: n = 211; validation dataset: n = 91) with pathologically confirmed HCC who underwent preoperative MR imaging were enrolled in this study. Three-dimensional regions of interest of the entire lesion were accessed by manually drawing along the tumor margins on the multiple sequences of MR images. Least absolute shrinkage and selection operator Cox regression were then applied to select ER-related radiomics features and construct radiomics signatures. Univariate analysis and multivariate Cox regression analysis were used to identify the significant clinico-radiological factors and establish a clinico-radiological model. A predictive model of ER incorporating the fusion radiomics signature and clinico-radiological risk factors was constructed. The diagnostic performance and clinical utility of this model were measured by receiver-operating characteristic (ROC), calibration curve, and decision curve analyses. Results The fusion radiomics signature consisting of 6 radiomics features achieved good prediction performance (training dataset: AUC = 0.85, validation dataset: AUC = 0.79). The predictive model of ER integrating clinico-radiological risk factors and the fusion radiomics signature improved the prediction efficacy with AUCs of 0.91 and 0.87 in the training and validation datasets, respectively. Furthermore, the nomogram and ER risk stratification system based on the predictive model demonstrated encouraging predictions of the individualized risk of ER and gave three risk groups with low, intermediate, or high risk of ER. Conclusions The proposed predictive model incorporating clinico-radiological factors and the fusion radiomics signature derived from multiparametric MR images may be an effective tool for the individualized prediction of postoperative ER in patients with HCC.
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Affiliation(s)
- Wencui Li
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Hongru Shen
- Tianjin Cancer Institute, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, Tianjin, China
| | - Lizhu Han
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Jiaxin Liu
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Bohan Xiao
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Xubin Li
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Zhaoxiang Ye
- Department of Radiology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
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Sun Y, Zhang H, Long J, Zhang Y, Zheng J, Yuan C. Percutaneous thermal ablation combined with transcatheter arterial chemoembolization for hepatitis C virus-related hepatocellular carcinoma: Efficacy and survival. Front Oncol 2022; 12:978614. [PMID: 36212462 PMCID: PMC9539218 DOI: 10.3389/fonc.2022.978614] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 09/05/2022] [Indexed: 12/24/2022] Open
Abstract
Objective The aim of this study was to investigate the efficacy and survival of Hepatitis C virus (HCV) -related hepatocellular carcinoma (HCC) undergoing percutaneous thermal ablation combined with transcatheter arterial chemoembolization (TACE). Methods A total of 83 HCV-related HCC patients who were treated with percutaneous thermal ablation combined with TACE were retrospectively analyzed. The demographic and clinical data were collected. The overall survival (OS) and recurrence free survival (RFS) rates were assessed by the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was used to assess independent risk factors of OS and RFS. Results 92.8% patients (77/83) and 96.6% (170/176) tumor lesions achieved complete response (CR) 1 month after all treatment, and 10.8% (9/83) patients had minor complications. The median OS was 60 months (95% confidence interval (CI)= 48.0-72.0), and the 1-, 2-, 3-, 5- and 10-year cumulative OS rates were 94%, 78.3%, 72.3%, 43.4% and 27.5%, respectively. The cumulative RFS rates at 1-, 2-, 3- and 5-year were 74.7%, 49.3%, 30.7% and 25.3%, respectively. Sex (HR =0.529, P=0.048), ablation result (HR=5.824, P=0.000) and Albumin-bilirubin (ALBI) score (HR=2.725, P=0.011) were independent prognostic factors for OS. Alpha-fetoprotein (AFP) (HR =2.360, P = 0.005) and tumor number(HR=2.786, P=0.000) were independent prognostic factors for RFS. Conclusions Percutaneous thermal ablation combined with TACE is a safe and effective treatment for HCV-related HCC. Sex, ablation result and ALBI are significant prognostic factors for OS. AFP and tumor number are significant prognostic factors for RFS.
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Osman AMA, Abdelaziz AO, Deweir M, Salah A, Harb STE, Nabeel MM, Abdelmaksoud AH, Shousha HI, Elbaz TM, Hashem MB. Hepatic resection versus microwave ablation for the treatment of early hepatocellular carcinoma: a comparative analysis of treatment outcomes and survival predictors. EGYPTIAN LIVER JOURNAL 2022; 12:48. [DOI: 10.1186/s43066-022-00210-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/16/2022] [Indexed: 11/10/2022] Open
Abstract
Abstract
Introduction
Liver resection and local ablation are the two primary curative treatments for early-stage hepatocellular carcinoma (HCC). Microwave ablation (MWA) shows promising performance in terms of early tumor response, recurrence, and survival. This study aims to determine whether MWA would be comparable to liver resection in treating early-stage HCC.
Methods
This study included patients with hepatitis C-related HCC attending the multidisciplinary HCC clinic, Kasr Al-Ainy Hospital (March 2018 to September 2020). We included adults with early-stage HCC (BCLC stages 0-A). We studied patients and tumor characteristics, HCC treatment response, recurrence, and overall survival.
Results
Thirty-one patients were treated with liver resection and 41 patients were treated with MWA, including 4 patients who received intraoperative MWA. By the end of the study, 21 patients (28.77%) died. Patients who underwent MWA were younger compared to the hepatectomy group with lower baseline AFP (21 (6.7–54) versus 77 (31.3–136.0), respectively, (P value 0.024) and tumor size (2.78 (0.87) cm versus 3.77 (0.97) cm, respectively, (P value < 0.001). We found no differences between the studied groups in terms of treatment response, post-treatment decompensation, recurrence, or overall survival. One-year survival probability in the MWA and resection groups was 75.5% and 76.3% respectively. Post-procedure hepatic decompensation was the only independent predictor of lower survival by multivariate logistic regression analysis (OR 37.74, 95%CI 6.251–227.87, P value < 0.001) after adjusting for age, AFP, and tumor size.
Conclusion
Liver resection and MWA showed similar satisfactory results in the treatment of early-stage HCC, in terms of treatment response, recurrence, and overall survival.
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Tian S, Su R, Wu K, Zhou X, Vadgama JV, Wu Y. Diaporine Potentiates the Anticancer Effects of Oxaliplatin and Doxorubicin on Liver Cancer Cells. J Pers Med 2022; 12:1318. [PMID: 36013267 PMCID: PMC9410505 DOI: 10.3390/jpm12081318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/13/2022] [Accepted: 08/13/2022] [Indexed: 11/26/2022] Open
Abstract
Recent studies have shown that diaporine, a novel fungal metabolic product, has a strong in vitro and in vivo anticancer effect on human non-small-cell lung and breast cancers. In this study, three human hepatocarcinoma cell lines (HepG2, Hep3B, and Huh7) were used to evaluate the efficacy of diaporine alone and in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin for the treatment of liver cancer. We demonstrated that diaporine, oxaliplatin, and doxorubicin triggered a concentration- and time-dependent decrease in the number of HepG2 cells. Diaporine at a concentration of 2.5 μM showed almost 100% inhibition of cell counts at 72 h. Similar effects were observed only with much higher concentrations (100 μM) of oxaliplatin or doxorubicin. Decreases in cell numbers after 48 h treatment with diaporine, oxaliplatin, and doxorubicin were also demonstrated in two additional hepatoma cell lines, Hep3B and Huh7. The combination of these drugs at low concentration for 48 h in vitro noticeably showed that diaporine improved the inhibitory effect on the number of cancer cells induced by oxaliplatin or doxorubicin. Additionally, this combination effectively inhibited colony growth in vitro. We found that inhibition of phosphorylation of ERK1/2 significantly increased when diaporine was used in combination with other agents. In addition, we also found that when diaporine was used in combination with doxorubicin or oxaliplatin, their proapoptotic effect greatly increased. We further revealed that the induction of apoptosis in hepatoma cells after treatment is due, at least in part, to the inhibition of phosphorylation of AKT, leading to the activation of caspase-3, inactivation of poly (ADP-ribose) polymerase (PARP), and subsequently to DNA damage, as indicated by the increased level of H2AX. Based on these findings, we suggest that diaporine in combination with the standard cytotoxic drugs oxaliplatin and doxorubicin may play a role in the treatment of liver cancer.
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Affiliation(s)
- Shiliu Tian
- Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China
- Fujian Sports Vocational Education and Technical College, Fuzhou 350001, China
| | - Rui Su
- College of Engineering, University of California, Berkeley, CA 94720, USA
| | - Ke Wu
- David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer Center, Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90095, USA
| | - Xuhan Zhou
- Fulgent Life Inc., Irvine, CA 92620, USA
| | - Jaydutt V. Vadgama
- David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer Center, Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90095, USA
| | - Yong Wu
- David Geffen UCLA School of Medicine and UCLA Jonsson Comprehensive Cancer Center, Division of Cancer Research and Training, Department of Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90095, USA
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Renzulli M, Pecorelli A, Brandi N, Marasco G, Adduci F, Tovoli F, Stefanini B, Granito A, Golfieri R. Radiological Features of Microvascular Invasion of Hepatocellular Carcinoma in Patients with Non-Alcoholic Fatty Liver Disease. GASTROENTEROLOGY INSIGHTS 2022; 13:275-285. [DOI: 10.3390/gastroent13030028] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2024] Open
Abstract
Background: The aim of the present study was to evaluate the presence and the prognostic value of the radiological signs of microvascular invasion (MVI) of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). Methods: Between January 2015 and December 2017, all patients (91 patients) with de novo HCC or HCC recurrence occurring at least 2 years after the last treatment in NAFLD (36 patients) or with hepatitis C virus (HCV) liver disease (55 patients) were included. Each HCC was treated with liver resection and transplantation to obtain the anatomopathological confirmation of MVI. All patients had at least one available computed tomography (CT) scan or magnetic resonance imaging (MRI) performed no more than one month prior to the treatment. The clinical data of each patient, tumor burden (diameter, margins, two-trait predictor of venous invasion (TTPVI), and peritumoral enhancement), the recurrence rate (RR) after a 1-year follow-up, and the time to recurrence (TTR) were collected. Results: The NAFLD–HCC nodules were larger as compared to HCV–HCC (51 mm vs. 36 mm, p = 0.004) and showed a higher prevalence of TTPVI (38.9 vs. 20.0%, p = 0.058). At multivariate analysis, nodule diameter >50 mm was found to be the only independent prognostic factor of TTPVI (hazard ratio: 21.3, 95% confidence interval: 4.2–107.7, p < 0.001), and the presence of TTPVI was confirmed to be the only independent prognostic factors of recurrence (hazard ratio: 2.349, 95% confidence interval: 1.369–4.032, p = 0.002). No correlations were found between TTR and irregular tumor margins or peritumoral enhancement. Conclusion: The NAFLD–HCC patients had larger tumors at diagnosis and showed a more frequent presence of radiological signs of MVI as compared to the HCV–HCC patients. The MVI was related to a more rapid recurrence after curative treatments, demonstrating the prognostic value of this radiological diagnosis.
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Affiliation(s)
- Matteo Renzulli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Anna Pecorelli
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Nicolò Brandi
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Giovanni Marasco
- Internal Medicine and Digestive Physiopathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Francesco Adduci
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
| | - Francesco Tovoli
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Bernardo Stefanini
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Alessandro Granito
- Division of Internal Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Rita Golfieri
- Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni 15, 40138 Bologna, Italy
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Wu CH, Lee YH, Liang PC, Hu RH, Shih TTF, Ho MC. Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma. J Formos Med Assoc 2022; 121:1550-1559. [PMID: 35033411 DOI: 10.1016/j.jfma.2021.12.026] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 08/27/2021] [Accepted: 12/28/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND/PURPOSE Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. METHODS A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. RESULTS A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. CONCLUSION Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.
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Affiliation(s)
- Chih-Horng Wu
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Yu-Hsin Lee
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Po-Chin Liang
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Rey-Heng Hu
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tiffany Ting-Fang Shih
- Department of Medical Imaging, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Department of Radiology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Chih Ho
- Department of Surgery, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan; Center for Functional Image and Interventional Image, National Taiwan University, Taipei, Taiwan; Department of Surgery, National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
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Zanotti S, Boot GF, Coto-Llerena M, Gallon J, Hess GF, Soysal SD, Kollmar O, Ng CKY, Piscuoglio S. The Role of Chronic Liver Diseases in the Emergence and Recurrence of Hepatocellular Carcinoma: An Omics Perspective. Front Med (Lausanne) 2022; 9:888850. [PMID: 35814741 PMCID: PMC9263082 DOI: 10.3389/fmed.2022.888850] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 05/23/2022] [Indexed: 12/02/2022] Open
Abstract
Hepatocellular carcinoma (HCC) typically develops from a background of cirrhosis resulting from chronic inflammation. This inflammation is frequently associated with chronic liver diseases (CLD). The advent of next generation sequencing has enabled extensive analyses of molecular aberrations in HCC. However, less attention has been directed to the chronically inflamed background of the liver, prior to HCC emergence and during recurrence following surgery. Hepatocytes within chronically inflamed liver tissues present highly activated inflammatory signaling pathways and accumulation of a complex mutational landscape. In this altered environment, cells may transform in a stepwise manner toward tumorigenesis. Similarly, the chronically inflamed environment which persists after resection may impact the timing of HCC recurrence. Advances in research are allowing an extensive epigenomic, transcriptomic and proteomic characterization of CLD which define the emergence of HCC or its recurrence. The amount of data generated will enable the understanding of oncogenic mechanisms in HCC from the CLD perspective and provide the possibility to identify robust biomarkers or novel therapeutic targets for the treatment of primary and recurrent HCC. Importantly, biomarkers defined by the analysis of CLD tissue may permit the early detection or prevention of HCC emergence and recurrence. In this review, we compile the current omics based evidence of the contribution of CLD tissues to the emergence and recurrence of HCC.
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Affiliation(s)
- Sofia Zanotti
- Anatomic Pathology Unit, IRCCS Humanitas University Research Hospital, Milan, Italy
| | - Gina F. Boot
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Mairene Coto-Llerena
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
- Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
| | - John Gallon
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
| | - Gabriel F. Hess
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Savas D. Soysal
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Otto Kollmar
- Clarunis, University Center for Gastrointestinal and Liver Diseases, St. Clara Hospital and University Hospital Basel, Basel, Switzerland
| | - Charlotte K. Y. Ng
- Department for BioMedical Research, University of Bern, Bern, Switzerland
- Swiss Institute of Bioinformatics, Lausanne, Switzerland
- Bern Center for Precision Medicine, Bern, Switzerland
| | - Salvatore Piscuoglio
- Visceral Surgery and Precision Medicine Research Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland
- Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland
- *Correspondence: Salvatore Piscuoglio
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Wang Y, Luo S, Jin G, Fu R, Yu Z, Zhang J. Preoperative clinical-radiomics nomogram for microvascular invasion prediction in hepatocellular carcinoma using
18
F-FDG PET/CT. BMC Med Imaging 2022; 22:70. [PMID: 35428272 PMCID: PMC9013080 DOI: 10.1186/s12880-022-00796-4] [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] [Received: 02/14/2022] [Accepted: 04/05/2022] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To develop a clinical-radiomics nomogram by incorporating radiomics score and clinical predictors for preoperative prediction of microvascular invasion in hepatocellular carcinoma. METHODS A total of 97 HCC patients were retrospectively enrolled from Shanghai Universal Medical Imaging Diagnostic Center and Changhai Hospital Affiliated to the Second Military Medical University. 909 CT and 909 PET slicers from 97 HCC patients were divided into a training cohort (N = 637) and a validation cohort (N = 272). Radiomics features were extracted from each CT or PET slicer, and features selection was performed with least absolute shrinkage and selection operator regression and radiomics score was also generated. The clinical-radiomics nomogram was established by integrating radiomics score and clinical predictors, and the performance of the models were evaluated from its discrimination ability, calibration ability, and clinical usefulness. RESULTS The radiomics score consisted of 45 selected features, and age, the ratio of maximum to minimum tumor diameter, and18 F-FDG uptake status were independent predictors of microvascular invasion. The clinical-radiomics nomogram showed better performance for MVI detection (0.890 [0.854, 0.927]) than the clinical nomogram (0.849 [0.804, 0.893]) (p < 0.05 ). Both nomograms showed good calibration and the clinical-radiomics nomogram's clinical practicability outperformed the clinical nomogram. CONCLUSIONS With the combination of radiomics score and clinical predictors, the clinical-radiomics nomogram can significantly improve the predictive efficacy of microvascular invasion in hepatocellular carcinoma (p < 0.05 ) compared with clinical nomogram.
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Affiliation(s)
- Yutao Wang
- The Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang Province 315020 China
- Shanghai Universal Medical Imaging Diagnostic Center, Shanghai University, Building 8, 406 Guilin Road, Xuhui District, Shanghai, 201103 China
| | - Shuying Luo
- Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang Province 315211 China
| | - Gehui Jin
- Medical School, Ningbo University, Ningbo, Zhejiang Province 315211 China
| | - Randi Fu
- Faculty of Electrical Engineering and Computer Science, Ningbo University, Ningbo, Zhejiang Province 315211 China
| | - Zhongfei Yu
- Shanghai Universal Medical Imaging Diagnostic Center, Shanghai University, Building 8, 406 Guilin Road, Xuhui District, Shanghai, 201103 China
| | - Jian Zhang
- Shanghai Universal Medical Imaging Diagnostic Center, Shanghai University, Building 8, 406 Guilin Road, Xuhui District, Shanghai, 201103 China
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Li X, Liu Z, Wei X, Lin J, Yang Q, Xie Y. Comprehensive Analysis of the Expression and Clinical Significance of THO Complex Members in Hepatocellular Carcinoma. Int J Gen Med 2022; 15:2695-2713. [PMID: 35300138 PMCID: PMC8922240 DOI: 10.2147/ijgm.s349925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2021] [Accepted: 02/21/2022] [Indexed: 11/23/2022] Open
Abstract
Background Methods Results Conclusion
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Affiliation(s)
- Xixi Li
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Zefeng Liu
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Xin Wei
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Jie Lin
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Qiwei Yang
- Medical Research Center, The Second Hospital of Jilin University, Changchun, People’s Republic of China
| | - Yingjun Xie
- Department of Hepatobiliary and Pancreatic Surgery, The Second Hospital of Jilin University, Changchun, People’s Republic of China
- Correspondence: Yingjun Xie, Tel +86 17390069233, Email
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Sun X, Hou Z, Li N, Zhang S. MiR-597-5p suppresses the progression of hepatocellular carcinoma via targeting transcriptional enhancer associate domain transcription factor 1 (TEAD1). In Vitro Cell Dev Biol Anim 2022; 58:96-108. [PMID: 35169903 DOI: 10.1007/s11626-021-00614-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Accepted: 08/01/2021] [Indexed: 11/05/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high incidence and mortality. MiR-597-5p is downregulated in tumor tissues of HCC compared with non-tumor tissues. However, its role in HCC is still unknown. This study aims to assess the function of miR-597-5p in HCC development and investigate the underlying mechanism. To perform gain- and loss-of-function studies, SK-HEP-1 cells and Huh-7 cells were transfected with miR-597-5p mimics and inhibitor, respectively. MiR-597-5p markedly reduced the cell viability and the expression of Ki-67 in HCC cells. MiR-597-5p also repressed the cell cycle progression of HCC cells and the protein levels of cyclin D1 and CDK2. Moreover, miR597-5p inhibited the migration and invasion of HCC cells and decreased MMP2 and MMP9 levels. Transcriptional enhancer associate domain transcription factor 1 (TEAD1) was identified as a target of miR-597-5p by luciferase reporter assay. TEAD1 and its downstream target genes, CTGF and CYR61, were downregulated by miR-597-5p in HCC cells. Furthermore, miR-597-5p was demonstrated to function in HCC progression by targeting TEAD1 via TEAD1 expression gain and loss. Our study demonstrates that miR-597-5p represses the proliferation, migration, and invasion of HCC cells through targeting TEAD1, which provides a therapeutic target for HCC treatment.
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Affiliation(s)
- Xiaogang Sun
- The Second Department of General Surgery, Jincheng People's Hospital, 456 Wenchang East Street, Jincheng, 048026, Shanxi, China
| | - Zhiyun Hou
- The Second Department of General Surgery, Jincheng People's Hospital, 456 Wenchang East Street, Jincheng, 048026, Shanxi, China.
| | - Ning Li
- The Second Department of General Surgery, Jincheng People's Hospital, 456 Wenchang East Street, Jincheng, 048026, Shanxi, China
| | - Shuangwei Zhang
- The Second Department of General Surgery, Jincheng People's Hospital, 456 Wenchang East Street, Jincheng, 048026, Shanxi, China
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Mohr I, Vogeler M, Pfeiffenberger J, Sprengel SD, Klauss M, Radeleff B, Teufel A, Chang DH, Springfeld C, Longerich T, Merle U, Mehrabi A, Weiss KH, Mieth M. Clinical effects and safety of different transarterial chemoembolization methods for bridging and palliative treatments in hepatocellular carcinoma. J Cancer Res Clin Oncol 2022; 148:3163-3174. [PMID: 35076764 PMCID: PMC9508038 DOI: 10.1007/s00432-021-03900-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Accepted: 12/24/2021] [Indexed: 01/09/2023]
Abstract
Purpose We assessed and compared clinical effects and safety endpoints of three methods of transarterial chemoembolization (TACE), conventional (cTACE), with drug-eluting beads (DEB-TACE), and with degradable starch microspheres (DSM-TACE), used in patients with hepatocellular carcinoma (HCC) in the bridging to liver transplant (LT) and the palliative setting. Methods In our center, 148 patients with HCC underwent 492 completed TACE procedures between 2008 and 2017 (158 for bridging to LT; 334 for palliative treatment) which we analyzed retrospectively. Of these procedures, 348 were DEB-TACE, 60 cTACE, and 84 DSM-TACE. Results The cTACE procedure revealed a significantly longer period of hospitalization (p = 0.02), increased occurrence of nausea (p = 0.025), and rise in alanine transaminase (ALT) levels (p = 0.001), especially in the palliative setting. In the bridging to LT cohort, these clinical endpoints did not reach statistical significance. Conclusions The clinical safety of different TACE methods for HCC in both the palliative and the bridging to LT setting was equivalent. In the palliative setting, the cTACE procedure revealed an increased risk for adverse clinical effects such as nausea, elevation of ALT, and a prolonged period of hospitalization what might either be related to the systemic effects of the chemotherapeutic agent or to the differences in both collectives. Thus, further studies must be conducted on a larger number of TACE procedures to effectively explore the clinical side effects of the various TACE variants.
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Affiliation(s)
- Isabelle Mohr
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Marie Vogeler
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Jan Pfeiffenberger
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | | | - Miriam Klauss
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
| | - Boris Radeleff
- Department of Diagnostic and Interventional Radiology, Sana Klinikum Hof, Hof, Germany
| | - Andreas Teufel
- Department of Gastroenterology and Hepatology, Mannheim University Hospital, Mannheim, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - De-Hua Chang
- Department of Radiology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Christoph Springfeld
- Department of Medical Oncology, Heidelberg University Hospital, National Center for Tumor Diseases (NCT), Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Thomas Longerich
- Department of Pathology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Uta Merle
- Internal Medicine IV, Department of Gastroenterology, Heidelberg University Hospital, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Karl Heinz Weiss
- Internal Medicine, Salem Hospital Heidelberg, Heidelberg, Germany
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, INF 110, 69120, Heidelberg, Germany.
- Liver Cancer Center Heidelberg (LCCH), Heidelberg, Germany.
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Huang X, Zhu S, Zhang K, Tan W, Chen Y, Shang C. High Expression of Long Non-Coding RNA TMCO1-AS1 is Associated With Poor Prognosis of Hepatocellular Carcinoma. Front Mol Biosci 2022; 9:814058. [PMID: 35141283 PMCID: PMC8819098 DOI: 10.3389/fmolb.2022.814058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/07/2022] [Indexed: 12/24/2022] Open
Abstract
Background: The molecular pathways along with the clinical significance of long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC) remain uncertain. Our study sought to identify and characterize lncRNAs associated with HCC. Methods: LncRNA TMCO1-AS1 was identified by differential expression analysis, receiver operating characteristic (ROC) analysis, and univariate analysis using RNA sequencing and clinical information of HCC from the public database. Then clinical correlations and survival analysis were conducted to further appraise the prognostic significance of lncRNA TMCO1-AS1 in HCC. Hepatoma and adjoining normal tissues from 66 patients who received surgical operation at our center were used to verify the results of the bioinformatics analysis. A survival prognostic model was established combining TMCO1-AS1 expression and other clinical characteristics. Results: Bioinformatics analysis showed the aberrant high expression of TMCO1-AS1 in HCC tissue. TMCO1-AS1 expression was positively correlated with alpha-fetoprotein (AFP) level, vascular invasion, tumor stage, as well as tumor differentiation. Moreover, survival analysis found a significant inverse association between the expression of TMCO1-AS1 and the survival of patients with HCC. Cox analysis indicated that TMCO1-AS1 was an independent factor for HCC prognosis. Analysis of the HCC tissues from patients at our center provided results similar to those of the bioinformatics analysis. Risk models for overall survival (OS) and recurrence-free survival (RFS) incorporating TMCO1-AS1 exhibited better sensitivity and specificity than using clinical characteristics alone. Conclusion: High TMCO1-AS1 expression is significantly correlated with the unfavorable poor prognosis of HCC, indicating its potential of being a novel prognostic marker for HCC.
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Affiliation(s)
- Xuelian Huang
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Sicong Zhu
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Surgical Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Kelin Zhang
- Department of Surgical Intensive Care Unit, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Wenliang Tan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Yajin Chen
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Yajin Chen, ; Changzhen Shang,
| | - Changzhen Shang
- Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Yajin Chen, ; Changzhen Shang,
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Jiang C, Ma G, Liu Q, Song S. The value of preoperative 18F-FDG PET metabolic and volumetric parameters in predicting microvascular invasion and postoperative recurrence of hepatocellular carcinoma. Nucl Med Commun 2022; 43:100-107. [PMID: 34456318 DOI: 10.1097/mnm.0000000000001478] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Microvascular invasion (MVI) is very important in the evaluation of hepatocellular carcinoma (HCC), but diagnosis is determined by postoperative pathology; thus, preoperative noninvasive methods will play an active role. The purpose of the study was to assess the performance of metabolic parameters of preoperative 18F-fluorodeoxyglucose PET/computerized tomography (18F-FDG PET/CT) in the prediction of MVI and postoperative recurrence in primary hepatocellular carcinoma. METHODS We retrospectively collected 72 patients with HCC who have performed 18F-FDG PET/CT scan before partial hepatectomy between 2016 and 2019. We used both normal liver tissue and inferior vena cava as the reference background and combined with clinicopathological features, 18F-FDG PET/CT metabolic and volumetric indices to predict MVI and postoperative recurrence of primary HCC before surgery. RESULTS Twenty-one of the 72 patients recurred, in recurrent cases showed higher maximum standard uptake value (SUVmax), TNR (ratio of tumor SUVmax to mean SUV [SUVmean] of the background tissue), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) than nonrecurrence cases (P < 0.001). All 18F-FDG PET metabolic and volumetric indices for predicting postoperative HCC recurrence were significant on receiver-operating-characteristic (ROC) curve analyses (P < 0.05). TNRIVC, TNRNL, MTVIVC, MTVNL TLGIVC and TLGNL were significant factors for predicting MVI in HCC (P < 0.05). On multivariate analyses, MVI, SUVmax, TNRIVC, TNRNL, MTVIVC, MTVNL, TLGIVC and TLGNL (P < 0.05) are independent risk factors for predicting postoperative HCC recurrence. TNRIVC is the most relevant PET/CT parameter for predicting MVI in HCC, and MTVIVC is the most valuable for predicting postoperative HCC recurrence. Moreover, the PET/CT parameters are more accurate for prognosis with inferior vena cava as a reference background than with normal liver tissue. CONCLUSION 18F-FDG PET/CT metabolic and volumetric indices are effective predictors, and could noninvasively provide more comprehensive predictive information on MVI and postoperative recurrence of primary HCC before surgery.
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Affiliation(s)
- Chunjuan Jiang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Guang Ma
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Qiufang Liu
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
| | - Shaoli Song
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center
- Center for Biomedical Imaging
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai, China
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