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Zhi Y, Guo Y, Li S, He X, Wei H, Laster K, Wu Q, Zhao D, Xie J, Ruan S, Lemoine NR, Li H, Dong Z, Liu K. FBL promotes hepatocellular carcinoma tumorigenesis and progression by recruiting YY1 to enhance CAD gene expression. Cell Death Dis 2025; 16:348. [PMID: 40289107 PMCID: PMC12034760 DOI: 10.1038/s41419-025-07684-z] [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: 12/04/2024] [Revised: 04/13/2025] [Accepted: 04/17/2025] [Indexed: 04/30/2025]
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Accumulating evidence suggests that epigenetic dysregulation contributes to the initiation and progression of HCC. We aimed to investigate key epigenetic regulators that contribute to tumorigenesis and progression, providing a theoretical basis for targeted therapy for HCC. We performed a comprehensive epigenetic analysis of differentially expressed genes in LIHC from the TCGA database. We identified fibrillarin (FBL), an rRNA 2'-O-methyltransferase, as an essential contributor to HCC. A series of in vitro and in vivo biological experiments were performed to investigate the potential mechanisms of FBL. FBL knockdown suppressed the proliferation of HCC cells. In vivo studies using cell-derived xenograft (CDX), patient-derived xenograft (PDX), and diethylnitrosamine (DEN)-induced HCC models in Fbl liver-specific knockout mice demonstrated the critical role of FBL in HCC carcinogenesis and progression. Mechanistically, FBL regulates the expression of CAD in HCC cells by recruiting YY1 to the CAD promoter region. We also revealed that fludarabine phosphate is a novel inhibitor of FBL and can inhibit HCC growth in vitro and in vivo. The antitumor activity of lenvatinib has been shown to be synergistically enhanced by fludarabine phosphate. Our study highlights the cancer-promoting role of the FBL-YY1-CAD axis in HCC and identifies fludarabine phosphate as a novel inhibitor of FBL. A schematic diagram depicting the FBL-YY1-CAD signaling pathway and its regulatory role in HCC progression.
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Affiliation(s)
- Yafei Zhi
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
- Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou, China
- Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China
- Cancer Chemistry International Collaboration Laboratory, Zhengzhou, China
| | - Yan Guo
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Shiliang Li
- Innovation Center for AI and Drug Discovery, East China Normal University, Shanghai, China
| | - Xinyu He
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Huifang Wei
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Kyle Laster
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Qiong Wu
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Dengyun Zhao
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China
| | - Jinxin Xie
- Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China
| | - Shanshan Ruan
- Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China
| | - Nicholas R Lemoine
- Sino-British Research Centre for Molecular Oncology, National Centre for International Research in Cell and Gene Therapy; The School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
- Center for Cancer Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
| | - Honglin Li
- Innovation Center for AI and Drug Discovery, East China Normal University, Shanghai, China.
- Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.
- Lingang Laboratory, Shanghai, China.
| | - Zigang Dong
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
- Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou, China.
- Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China.
- Cancer Chemistry International Collaboration Laboratory, Zhengzhou, China.
| | - Kangdong Liu
- State Key Laboratory of Metabolic Dysregulation & Prevention and Treatment of Esophageal Cancer; The School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.
- China-US (Henan) Hormel Cancer Institute, Zhengzhou, China.
- Tianjian Laboratory of Advanced Biomedical Sciences, Zhengzhou, China.
- Innovation Center of Basic Research for Metabolic-Associated Fatty Liver Disease, Ministry of Education of China, Zhengzhou, China.
- Provincial Cooperative Innovation Center for Cancer Chemoprevention, Zhengzhou University, Zhengzhou, China.
- Cancer Chemistry International Collaboration Laboratory, Zhengzhou, China.
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Ro E, Schooler GR, Morin CE, Khanna G, Towbin AJ. Update on the imaging evaluation of pediatric liver tumors from the ACR Pediatric LI-RADS Working Group. Abdom Radiol (NY) 2025; 50:1171-1179. [PMID: 39292279 DOI: 10.1007/s00261-024-04565-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/19/2024]
Affiliation(s)
- Esther Ro
- Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, USA.
- Northwestern University Feinberg School of Medicine, Chicago, USA.
| | - Gary R Schooler
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
| | - Cara E Morin
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
| | - Geetika Khanna
- Emory University and Children's Healthcare of Atlanta, Atlanta, USA
| | - Alexander J Towbin
- Cincinnati Children's Hospital, Cincinnati, USA
- University of Cincinnati College of Medicine, Cincinnati, USA
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Xue Y, Shi B, Zhong J, Wang G, Wang J, An W, Qian Y, Su Z, Peng Z, Li H. Case report: A rare case of intragastric metastasis after liver transplantation for liver cancer. Front Oncol 2024; 14:1495517. [PMID: 39711953 PMCID: PMC11659134 DOI: 10.3389/fonc.2024.1495517] [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: 09/12/2024] [Accepted: 11/19/2024] [Indexed: 12/24/2024] Open
Abstract
A 13-year-old boy was admitted to Xiang'an Hospital of Xiamen University due to HBV-related liver cancer. Intrahepatic metastasis was considered to occur by CT scan. A gastroscope revealed esophagogastric variceal bleeding, and later, the patient underwent a successful liver transplantation. Fourteen months posttransplant, chest CT indicated lung metastasis, and the patient underwent thoracoscopic radical resection of lung cancer. Twenty-one months posttransplant, gastroscopy revealed a gastric fundus tumor growing into the gastric cavity. Proximal gastrectomy was performed, and pathology indicated moderately to poorly differentiated carcinoma without invasion of serosa, suggesting the first study to report HCC metastasis to the stomach lumen without invasion of serosa after LT. Currently, the alpha-fetoprotein (AFP) level of the patient has dropped below normal.
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Affiliation(s)
- Youfeng Xue
- Hepatobiliary Surgery Department, Fuqing Hospital, Fuzhou, Fujian, China
| | - Baojie Shi
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jianfa Zhong
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Guimei Wang
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Jie Wang
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Wenbin An
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Yunyun Qian
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Zhaojie Su
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Zhihai Peng
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
| | - Hao Li
- Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China
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Janssen FW, Lak NSM, Janda CY, Kester LA, Meister MT, Merks JHM, van den Heuvel-Eibrink MM, van Noesel MM, Zsiros J, Tytgat GAM, Looijenga LHJ. A comprehensive overview of liquid biopsy applications in pediatric solid tumors. NPJ Precis Oncol 2024; 8:172. [PMID: 39097671 PMCID: PMC11297996 DOI: 10.1038/s41698-024-00657-z] [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: 02/20/2024] [Accepted: 07/15/2024] [Indexed: 08/05/2024] Open
Abstract
Liquid biopsies are emerging as an alternative source for pediatric cancer biomarkers with potential applications during all stages of patient care, from diagnosis to long-term follow-up. While developments within this field are reported, these mainly focus on dedicated items such as a specific liquid biopsy matrix, analyte, and/or single tumor type. To the best of our knowledge, a comprehensive overview is lacking. Here, we review the current state of liquid biopsy research for the most common non-central nervous system pediatric solid tumors. These include neuroblastoma, renal tumors, germ cell tumors, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and other soft tissue sarcomas, and liver tumors. Within this selection, we discuss the most important or recent studies involving liquid biopsy-based biomarkers, anticipated clinical applications, and the current challenges for success. Furthermore, we provide an overview of liquid biopsy-based biomarker publication output for each tumor type based on a comprehensive literature search between 1989 and 2023. Per study identified, we list the relevant liquid biopsy-based biomarkers, matrices (e.g., peripheral blood, bone marrow, or cerebrospinal fluid), analytes (e.g., circulating cell-free and tumor DNA, microRNAs, and circulating tumor cells), methods (e.g., digital droplet PCR and next-generation sequencing), the involved pediatric patient cohort, and proposed applications. As such, we identified 344 unique publications. Taken together, while the liquid biopsy field in pediatric oncology is still behind adult oncology, potentially relevant publications have increased over the last decade. Importantly, steps towards clinical implementation are rapidly gaining ground, notably through validation of liquid biopsy-based biomarkers in pediatric clinical trials.
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Affiliation(s)
| | | | | | | | - Michael T Meister
- Princess Máxima Center, Utrecht, the Netherlands
- Oncode Institute, Utrecht, the Netherlands
| | - Johannes H M Merks
- Princess Máxima Center, Utrecht, the Netherlands
- Division of Imaging and Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands
| | - Marry M van den Heuvel-Eibrink
- Princess Máxima Center, Utrecht, the Netherlands
- Wilhelmina Children's Hospital-Division of CHILDHEALTH, University Medical Center Utrech, University of Utrecht, Utrecht, the Netherlands
| | - Max M van Noesel
- Princess Máxima Center, Utrecht, the Netherlands
- Division of Imaging and Oncology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands
| | | | - Godelieve A M Tytgat
- Princess Máxima Center, Utrecht, the Netherlands
- Department of Genetics, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands
| | - Leendert H J Looijenga
- Princess Máxima Center, Utrecht, the Netherlands.
- Department of Pathology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands.
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Gambella A, Kalantari S, Cadamuro M, Quaglia M, Delvecchio M, Fabris L, Pinon M. The Landscape of HNF1B Deficiency: A Syndrome Not Yet Fully Explored. Cells 2023; 12:cells12020307. [PMID: 36672242 PMCID: PMC9856658 DOI: 10.3390/cells12020307] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/05/2023] [Accepted: 01/10/2023] [Indexed: 01/15/2023] Open
Abstract
The hepatocyte nuclear factor 1β (HNF1B) gene is involved in the development of specialized epithelia of several organs during the early and late phases of embryogenesis, performing its function mainly by regulating the cell cycle and apoptosis pathways. The first pathogenic variant of HNF1B (namely, R177X) was reported in 1997 and is associated with the maturity-onset diabetes of the young. Since then, more than 230 different HNF1B variants have been reported, revealing a multifaceted syndrome with complex and heterogenous genetic, pathologic, and clinical profiles, mainly affecting the pediatric population. The pancreas and kidneys are the most frequently affected organs, resulting in diabetes, renal cysts, and a decrease in renal function, leading, in 2001, to the definition of HNF1B deficiency syndrome, including renal cysts and diabetes. However, several other organs and systems have since emerged as being affected by HNF1B defect, while diabetes and renal cysts are not always present. Especially, liver involvement has generally been overlooked but recently emerged as particularly relevant (mostly showing chronically elevated liver enzymes) and with a putative relation with tumor development, thus requiring a more granular analysis. Nowadays, HNF1B-associated disease has been recognized as a clinical entity with a broader and more variable multisystem phenotype, but the reasons for the phenotypic heterogeneity are still poorly understood. In this review, we aimed to describe the multifaceted nature of HNF1B deficiency in the pediatric and adult populations: we analyzed the genetic, phenotypic, and clinical features of this complex and misdiagnosed syndrome, covering the most frequent, unusual, and recently identified traits.
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Affiliation(s)
- Alessandro Gambella
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
- Division of Liver and Transplant Pathology, University of Pittsburgh, Pittsburgh, PA 15232, USA
| | - Silvia Kalantari
- Department of Medical Sciences, University of Turin, 10126 Turin, Italy
| | | | - Marco Quaglia
- Department of Translational Medicine, University of Piemonte Orientale, 28100 Novara, Italy
| | - Maurizio Delvecchio
- Metabolic Disease and Genetics Unit, Giovanni XXIII Children’s Hospital, AOU Policlinico di Bari, 70124 Bari, Italy
- Correspondence:
| | - Luca Fabris
- Department of Molecular Medicine, University of Padova, 35121 Padua, Italy
- Liver Center, Digestive Disease Section, Department of Internal Medicine, Yale University, New Haven, CT 06510, USA
| | - Michele Pinon
- Pediatric Gastroenterology Unit, Regina Margherita Children’s Hospital, AOU Città della Salute e della Scienza di Torino, 10126 Turin, Italy
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The Expressions and Functions of lncRNA Related to m6A in Hepatocellular Carcinoma from a Bioinformatics Analysis. COMPUTATIONAL AND MATHEMATICAL METHODS IN MEDICINE 2022; 2022:1395557. [PMID: 36276996 PMCID: PMC9581679 DOI: 10.1155/2022/1395557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Accepted: 09/20/2022] [Indexed: 11/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancer in these days. Besides, N6-methyladenosine (m6A) plays an important role in the occurrence and development of hepatocellular carcinoma. Meanwhile, it is known to us that long noncoding RNAs (lncRNA) have the capability to control the expression of genes which means some lncRNA can adjust the expression of some m6A.Thus, it is indispensable to dig the m6A-related lncRNA in hepatocellular carcinoma about its potential regulatory mechanism and immune analysis as well as its potential drugs. In this experiment, expression profile and clinical information of lncRNA are obtained by downloading the liver cancer data set from The Cancer Genome Atlas (TCGA) database. GO enrichment analysis is used to predict potential regulatory mechanism of lncRNA. Correlation analysis of clinical parameters are calculated via chisq.test. The Cox regression model is used in univariate and multivariate analysis, and the difference is statistically significant when P < 0.05. The results show that many kinds of lncRNA have influence on the prognosis of patients with HCC, and enrichment analysis discloses some pathways that can be used to evaluate mechanism underlying in HCC. The screening of targeted drugs can provide new clues for further experiments and clinical treatment.
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Falqueto LE, Vilar PR, Campos HG, Schulz C, Mattos E Silva EDE. Primary Malignant Liver Tumors: eight-year experience in a Pediatric Hospital in Brazil. A cross-sectional study. Rev Col Bras Cir 2022; 49:e20223273. [PMID: 35703678 PMCID: PMC10578837 DOI: 10.1590/0100-6991e-20223273-en] [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: 01/13/2022] [Accepted: 03/22/2022] [Indexed: 11/21/2022] Open
Abstract
INTRODUCTION liver tumors are rare neoplasms in childhood (1-2%), and about 2/3 are malignant. Hepatoblastoma (HB) is the most frequent, followed by hepatocellular carcinoma (HCC). In both, the main treatment is surgical resection. Currently, chemotherapy and liver transplantation have improved outcomes. OBJECTIVE study of the epidemiological profile and evolution of liver cancer cases in a referral pediatric hospital. METHODOLOGY a retrospective survey of medical records of patients aged up to 18 years with a diagnosis of primary malignant hepatic neoplasm between 2012 and 2020, carried out in the largest exclusively pediatric hospital in Brazil. RESULTS a total of 13 patients with malignant liver tumors (HB 12, HCC 1) were treated. Of the HB cases, 66,7% were male, with a mean age of 2 years and the main alteration in the palpable abdominal mass. Tumors involved an average of 3 liver segments, more in the right lobe (54%). Only one patient was treated with surgery without neoadjuvant therapy, another one underwent transplantation like the first treatment, and another 2 required liver transplantation as a rescue. The middle follow-up time of patients with HB was 39 months and only 1 case died due to febrile neutropenia. The 5-year overall and disease-free survival was 91.7% and 81.5%, respectively. CONCLUSION Advanced staging at the time of diagnosis has always been a poor prognostic factor in patients with primary malignant liver tumors. However, the results and survival have improved with the advancement of chemotherapy, surgical technique, and liver transplantation.
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Affiliation(s)
| | - Paula Rubio Vilar
- - Hospital Pequeno Príncipe, Cirurgia Pediátrica - Curitiba - PR - Brasil
| | | | - Claudio Schulz
- - Hospital Pequeno Príncipe, Cirurgia Pediátrica - Curitiba - PR - Brasil
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Jiang ZP, Zeng KY, Huang JY, Yang J, Yang R, Li JW, Qiu TT, Luo Y, Lu Q. Differentiating malignant and benign focal liver lesions in children using CEUS LI-RADS combined with serum alpha-fetoprotein. World J Gastroenterol 2022; 28:2350-2360. [PMID: 35800178 PMCID: PMC9185218 DOI: 10.3748/wjg.v28.i21.2350] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Revised: 02/08/2022] [Accepted: 04/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Contrast-enhanced ultrasound (CEUS) can be used to diagnose focal liver lesions (FLLs) in children. The America College of Radiology developed the CEUS liver imaging reporting and data system (LI-RADS) for standardizing CEUS diagnosis of FLLs in adult patients. Until now, no similar consensus or guidelines have existed for pediatric patients to improve imaging interpretation as adults. AIM To evaluate the performance of CEUS LI-RADS combined with alpha-fetoprotein (AFP) in differentiating benign and malignant FLLs in pediatric patients. METHODS Between January 2011 and January 2021, patients ≤ 18 years old who underwent CEUS for FLLs were retrospectively evaluated. The following criteria for diagnosing malignancy were proposed: Criterion I considered LR-4, LR-5, or LR-M lesions as malignancies; criterion II regarded LR-4, LR-5 or LR-M lesions with simultaneously elevated AFP (≥ 20 ng/mL) as malignancies; criterion III took LR-4 Lesions with elevated AFP or LR-5 or LR-M lesions as malignancies. The sensitivity, specificity, accuracy and area under the receiver operating characteristic curve (AUC) were calculated to determine the diagnostic value of the aforementioned criteria. RESULTS The study included 63 nodules in 60 patients (mean age, 11.0 ± 5.2 years; 26 male). There were no statistically significant differences between the specificity, accuracy, or AUC of criterion II and criterion III (95.1% vs 80.5%, 84.1% vs 87.3%, and 0.794 vs 0.902; all P > 0.017). Notably, criterion III showed a higher diagnostic sensitivity than criterion II (100% vs 63.6%; P < 0.017). However, both the specificity and accuracy of criterion I was inferior to those of criterion II and criterion III (all P < 0.017). For pediatric patients more than 5 years old, the performance of the three criteria was overall similar when patients were subcategorized by age when compared to all patients in aggregate. CONCLUSION CEUS LI-RADS combined with AFP may be a powerful diagnostic tool in pediatric patients. LR-4 with elevated AFP, LR-5 or LR-M lesions is highly suggestive of malignant tumors.
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Affiliation(s)
- Zhen-Peng Jiang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ke-Yu Zeng
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Yan Huang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jie Yang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Rui Yang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jia-Wu Li
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ting-Ting Qiu
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Yan Luo
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qiang Lu
- Department of Medical Ultrasound, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
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Sun K, Zhang L, Chen P, Qi D, Liu H, Bao H, Wang X, Li T. Circular RNA circ SET domain containing 2 (circSETD2) inhibits hepatocellular carcinoma cell proliferation and invasion in vivo and in vitro. Bioengineered 2022; 13:7293-7302. [PMID: 35260047 PMCID: PMC8974196 DOI: 10.1080/21655979.2022.2048577] [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] [Indexed: 11/16/2022] Open
Abstract
Liver cancer is a common malignant tumor with high incidence and mortality rates. However, a reliable prognostic signature has not yet been confirmed. Circular RNAs (circRNAs) play a role in the development and prognosis of numerous malignancies as well as liver cancer. Therefore, identifying abnormally expressed circRNAs in liver cancer tissue is essential for early diagnosis and treatment. This study found that circular RNA circ SET domain containing 2 (circSETD2) is abnormally expressed in liver cancer tissues, but the role and molecular mechanismsin the occurrence and development of liver cancer are still unclear. The expression level of circSETD2 was evaluated through Quantitative Real-time Polymerase chain reaction (qRT-PCR) in cancerous liver tissues (30 cases), liver cancer cell lines and para-cancerous tissues. Knockdown and overexpression circSETD2 lentiviral vector was constructed and applied to transfect hepatoma cells. Cell Counting Kit-8 (CCK-8), colony formation assay, flow cytometry and Transwell assay were used to examine the effects of circSETD2 overexpression or knockdown on liver cancer migration, invasion, cell cycle and cell proliferation. The tumourigenicity in vivo was utilized to assess the effect of circSETD2 on the proliferation of liver cancer cells. circSETD2 expression is lower in cell lines and liver cancer tissues. circSETD2 knockdown can considerably increase liver cancer cells’ invasion, proliferation and colony formation. While In vitro and in vivo, circSETD2 overexpression shows opposite effect. Western blot showed that circSETD2 knockdown can considerably promote E-cadherin expression and inhibit Vimentin, N-cadherin, matrix metallopeptidase-9 (MMP-9) and MMP-2 expression. These findings improve our understanding of the mechanisms of liver cancer progression and will guide future development of therapeutic strategies against the disease by targeting circ-SETD2.
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Affiliation(s)
- Keyan Sun
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Lei Zhang
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Peng Chen
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Debin Qi
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Hao Liu
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Haili Bao
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
| | - Xiongwei Wang
- Department of Neurosurgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Tao Li
- Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai China
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FALQUETO LORAINEENTRINGER, VILAR PAULARUBIO, CAMPOS HELDERGROENWOLD, SCHULZ CLAUDIO, MATTOS E SILVA ELISANGELADE. Neoplasias Malignas Primárias do Fígado: experiência de oito anos de um Hospital Pediátrico no Brasil. Estudo transversal. Rev Col Bras Cir 2022. [DOI: 10.1590/0100-6991e-20223273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
RESUMO Introdução: tumores hepáticos são neoplasias raras na infância (1-2%), sendo que cerca de 2/3 são malignos. O hepatoblastoma (HB) é o mais frequente, seguido do carcinoma hepatocelular (CHC). Em ambos, o principal tratamento é a ressecção cirúrgica completa. Atualmente, a quimioterapia e o transplante hepático têm melhorado os resultados. Objetivo: estudo do perfil epidemiológico e evolução dos casos de cânceres hepáticos em um hospital pediátrico de referência. Método: Levantamento retrospectivo de prontuários de pacientes até 18 anos com diagnóstico de neoplasia maligna primária hepática entre 2012 e 2020 realizado no maior hospital exclusivamente pediátrico do Brasil. Resultados: foram atendidos 13 pacientes com tumores malignos hepáticos (HB 12, CHC 1). Dos casos de HB, 66,7% eram do sexo masculino, com idade média de 2 anos e a principal alteração foi massa abdominal palpável. Os tumores envolviam em média 3 segmentos hepáticos, mais em lobo direito (54%). Um paciente foi tratado com cirurgia sem neoadjuvância, um foi submetido a transplante inicialmente e outros 2 necessitaram de transplante hepático como resgate. O tempo de seguimento dos pacientes com HB foi de 39 meses e apenas 1 caso foi a óbito por neutropenia febril. A sobrevida geral e livre de doença em 5 anos foi de 91,7% e 81,5% respectivamente. Conclusão: o estadiamento avançado no momento do diagnóstico sempre foi um fator de mau prognóstico em pacientes com tumores hepáticos malignos primários. Entretanto, os resultados e a sobrevida têm melhorado significativamente com o avanço da quimioterapia, da técnica cirúrgica e do transplante hepático.
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Wang X, Ma Q, Wen C, Gong T, Li J, Liang W, Li M, Wang Y, Guo R. Folic acid and deoxycholic acid derivative modified Fe 3O 4 nanoparticles for efficient pH-dependent drug release and multi-targeting against liver cancer cells. RSC Adv 2021; 11:39804-39812. [PMID: 35494148 PMCID: PMC9044570 DOI: 10.1039/d1ra05874f] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 11/17/2021] [Indexed: 12/23/2022] Open
Abstract
The novel nano-drug carrier (FDCA-FA-MNPs) was constructed by grafting formyl deoxycholic acid (FDCA) and folic acid (FA) on the surface of Fe3O4 magnetic nanoparticles (MNPs), possessing the advantages of superparamagnetism, good stability, low cytotoxicity and good blood compatibility. The hydrophobic anti-cancer drug doxorubicin hydrochloride (DOX) was successfully loaded onto FDCA-FA-MNPs through supramolecular interactions (hydrogen bond between FDCA and drug and hydrophobic interaction and π-π stacking between drug and drug). The drug loading amount and drug loading capacity were 509.1 mg g-1 and 33.73 wt%, respectively. In addition, drug release had a pH responsive and controllable release performance, the release rate at pH 5.3 (45.6%) was four times that at pH 7.4 (11.5%), and the tumor microenvironment was favorable for drug release. More importantly, the novel nano-drug carrier combined the hepatocellular targeting of FDCA, the cancer cell targeting of FA, and the magnetic targeting of Fe3O4, showing excellent cancer-killing efficiency (78%) in vitro. Therefore, the nano-drug carrier synthesized in this paper has potential practical application value in the targeted therapy of liver cancer.
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Affiliation(s)
- Xiaoyu Wang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
| | - Qing Ma
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
| | - Chaochao Wen
- Institute of Environmental Science, Department of Chemistry, Shanxi University Taiyuan 030006 China
| | - Tao Gong
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
| | - Jing Li
- Institute of Environmental Science, Department of Chemistry, Shanxi University Taiyuan 030006 China
| | - Wenting Liang
- Institute of Environmental Science, Department of Chemistry, Shanxi University Taiyuan 030006 China
| | - Meining Li
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
| | - Yuyao Wang
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
| | - Rui Guo
- Department of Biochemistry and Molecular Biology, Shanxi Medical University Taiyuan 030001 China
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Sintusek P, Phewplung T, Sanpavat A, Poovorawan Y. Liver tumors in children with chronic liver diseases. World J Gastrointest Oncol 2021; 13:1680-1695. [PMID: 34853643 PMCID: PMC8603454 DOI: 10.4251/wjgo.v13.i11.1680] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/27/2021] [Accepted: 08/23/2021] [Indexed: 02/06/2023] Open
Abstract
Liver tumors are rare in children, but the incidence may increase in some circumstances and particularly in chronic liver diseases. Most liver tumors consequent to chronic liver diseases are malignant hepatocellular carcinoma. Other liver tumors include hepatoblastoma, focal nodular hyperplasia, adenoma, pseudotumor, and nodular regenerative hyperplasia. Screening of suspected cases is beneficial. Imaging and surrogate markers of alpha-fetoprotein are used initially as noninvasive tools for surveillance. However, liver biopsy for histopathology evaluation might be necessary for patients with inconclusive findings. Once the malignant liver tumor is detected in children with cirrhosis, liver transplantation is currently considered the preferred option and achieves favorable outcomes. Based on the current evidence, this review focuses on liver tumors with underlying chronic liver disease, their epidemiology, pathogenesis, early recognition, and effective management.
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Affiliation(s)
- Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit, Department of Pediatrics, Division of Gastroenterology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok 10330, Thailand
| | - Teerasak Phewplung
- Department of Radiology, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Anapat Sanpavat
- Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
| | - Yong Poovorawan
- Center of Excellence in Clinical Virology, Chulalongkorn University, Bangkok 10330, Thailand
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