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Ramadan A, Kaddah M, Shousha H, El-Kassas M. Personalized treatment approaches in hepatocellular carcinoma. Arab J Gastroenterol 2025; 26:122-128. [PMID: 39765390 DOI: 10.1016/j.ajg.2024.08.003] [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: 02/24/2024] [Revised: 07/13/2024] [Accepted: 08/24/2024] [Indexed: 03/16/2025]
Abstract
Personalized medicine is an emerging field that provides novel approaches to disease's early diagnosis, prevention, treatment, and prognosis based on the patient's criteria in gene expression, environmental factors, lifestyle, and diet. To date, hepatocellular carcinoma (HCC) is a significant global health burden, with an increasing incidence and significant death rates, despite advancements in surveillance, diagnosis, and therapeutic approaches. The majority of HCC lesions develop in patients with liver cirrhosis, carrying the risks of mortality associated with both the tumor burden and the cirrhosis. New therapeutic agents involving immune checkpoint inhibitors and targeted agents have been developed for sequential or concomitant application for advanced HCC but only a tiny percentage of patients benefit from each approach. Moreover, clinicians encounter difficulties determining the most appropriate regimen for each patient. This emphasizes the need for a personalized treatment approach. In other words, patients should no longer undergo treatment based on their tumor's histology but depending on the distinct molecular targets specific to their tumor biology. However, the utilization of precision medicine in managing HCC is still challenging. This review aims to discuss the role of personalized medicine in diagnosing, managing, and defining the prognosis of HCC. We also discuss the role of liquid biopsy and their clinical applications for immunotherapies in HCC. More clinical studies are still necessary to improve the precision of biomarkers used in the treatment decision for patients with HCC.
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Affiliation(s)
- Ahmed Ramadan
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona Kaddah
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Hend Shousha
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed El-Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo, Egypt; Liver Disease Research Center, College of Medicine, King Saud University, Riyadh 11411, Saudi Arabia.
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Ma J, Yu Q, Van Ha T. Image-Guided Liver Biopsy: Perspectives from Interventional Radiology. Semin Intervent Radiol 2024; 41:500-506. [PMID: 39664226 PMCID: PMC11631366 DOI: 10.1055/s-0044-1792174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
Liver biopsy is a crucial aspect of interventional radiology and plays a significant role in the management of hepatobiliary diseases. Radiologists commonly perform two major image-guided liver biopsy techniques: percutaneous and transjugular approaches. It is essential for radiologists to understand the role of liver biopsy in diagnosing and treating hepatobiliary conditions, the procedural details involved, and how to manage potential complications. This article reviews the indications, contraindications, techniques, and efficacy of image-guided liver biopsy, with a focus on both percutaneous and transjugular methods.
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Affiliation(s)
- Jingqin Ma
- Department of Interventional Radiology, Shanghai Medical School of Fudan University, Zhongshan Hospital, Shanghai, People's Republic of China
| | - Qian Yu
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
| | - Thuong Van Ha
- Department of Radiology, University of Chicago Medical Center, University of Chicago, Chicago, Illinois
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3
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Liao S, Wang Q, Chen S, Huang Q, Zhou L, Liu H, He S, Zhou Z. Mito-LND and (E)-Akt inhibitor-IV: novel compounds inducing endoplasmic reticulum stress and ROS accumulation against hepatocellular carcinoma. J Transl Med 2024; 22:792. [PMID: 39198815 PMCID: PMC11351498 DOI: 10.1186/s12967-024-05545-5] [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: 01/17/2024] [Accepted: 07/29/2024] [Indexed: 09/01/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality. Although multi-kinase inhibitors can prolong the overall survival of late-stage HCC patients, the emergence of drug resistance diminishes these benefits, ultimately resulting in treatment failure. Therefore, there is an urgent need for novel and effective drugs to impede the progression of liver cancer. METHODS This study employed a concentration gradient increment method to establish acquired sorafenib or regorafenib-resistant SNU-449 cells. Cell viability was assessed using the cell counting kit-8 assay. A library of 793 bioactive small molecules related to metabolism screened compounds targeting both parental and drug-resistant cells. The screened compounds will be added to both the HCC parental cells and the drug-resistant cells, followed by a comprehensive assessment. Intracellular adenosine triphosphate (ATP) levels were quantified using kits. Flow cytometry was applied to assess cell apoptosis and reactive oxygen species (ROS). Real-time quantitative PCR studied relative gene expression, and western blot analysis assessed protein expression changes in HCC parental and drug-resistant cells. A xenograft model in vivo evaluated Mito-LND and (E)-Akt inhibitor-IV effects on liver tumors, with hematoxylin and eosin staining for tissue structure and immunohistochemistry staining for endoplasmic reticulum stress protein expression. RESULTS From the compound library, we screened out two novel compounds, Mito-LND and (E)-Akt inhibitor-IV, which could potently kill both parental cells and drug-resistant cells. Mito-LND could significantly suppress proliferation and induce apoptosis in HCC parental and drug-resistant cells by upregulating glycolytic intermediates and downregulating those of the tricarboxylic acid (TCA) cycle, thereby decreasing ATP production and increasing ROS. (E)-Akt inhibitor-IV achieved comparable results by reducing glycolytic intermediates, increasing TCA cycle intermediates, and decreasing ATP synthesis and ROS levels. Both compounds trigger apoptosis in HCC cells through the interplay of the AMPK/MAPK pathway and the endoplasmic reticulum stress response. In vivo assays also showed that these two compounds could significantly inhibit the growth of HCC cells and induce endoplasmic reticulum stress. CONCLUSION Through high throughput screening, we identified that Mito-LND and (E)-Akt inhibitor-IV are two novel compounds against both parental and drug-resistant HCC cells, which could offer new strategies for HCC patients.
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Affiliation(s)
- Siqi Liao
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qingliang Wang
- The Department of Pathology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Siyuan Chen
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qixuan Huang
- The Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Li Zhou
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hongtao Liu
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Song He
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
| | - Zhihang Zhou
- The Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Fang H, Xu H, Yu J, Cao H, Li L. Human Hepatobiliary Organoids: Recent Advances in Drug Toxicity Verification and Drug Screening. Biomolecules 2024; 14:794. [PMID: 39062508 PMCID: PMC11274902 DOI: 10.3390/biom14070794] [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: 05/02/2024] [Revised: 06/08/2024] [Accepted: 07/01/2024] [Indexed: 07/28/2024] Open
Abstract
Many drug and therapeutic modalities have emerged over the past few years. However, successful commercialization is dependent on their safety and efficacy evaluations. Several preclinical models are available for drug-screening and safety evaluations, including cellular- and molecular-level models, tissue and organoid models, and animal models. Organoids are three-dimensional cell cultures derived from primary tissues or stem cells that are structurally and functionally similar to the original organs and can self-renew, and they are used to establish various disease models. Human hepatobiliary organoids have been used to study the pathogenesis of diseases, such as hepatitis, liver fibrosis, hepatocellular carcinoma, primary sclerosing cholangitis and biliary tract cancer, as they retain the physiological and histological characteristics of the liver and bile ducts. Here, we review recent research progress in validating drug toxicity, drug screening and personalized therapy for hepatobiliary-related diseases using human hepatobiliary organoid models, discuss the challenges encountered in current research and evaluate the possible solutions.
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Affiliation(s)
- Haoyu Fang
- Department of Pathology and Pathophysiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, China;
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; (J.Y.); (L.L.)
| | - Haoying Xu
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China;
| | - Jiong Yu
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; (J.Y.); (L.L.)
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China;
- Zhejiang Key Laboratory for Diagnosis and Treatment of Physic-Chemical and Aging-Related Injuries, 79 Qingchun Rd., Hangzhou 310003, China
| | - Hongcui Cao
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; (J.Y.); (L.L.)
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China;
- Zhejiang Key Laboratory for Diagnosis and Treatment of Physic-Chemical and Aging-Related Injuries, 79 Qingchun Rd., Hangzhou 310003, China
| | - Lanjuan Li
- Jinan Microecological Biomedicine Shandong Laboratory, Jinan 250117, China; (J.Y.); (L.L.)
- State Key Laboratory for the Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Rd., Hangzhou 310003, China;
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Hou C, Xiong B, Zhou L, Fei Y, Shi C, Zhu X, Xie T, Wu Y. Transarterial chemoembolization with molecular targeted therapies plus camrelizumab for recurrent hepatocellular carcinoma. BMC Cancer 2024; 24:387. [PMID: 38539150 PMCID: PMC10967172 DOI: 10.1186/s12885-024-12144-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Accepted: 03/19/2024] [Indexed: 11/11/2024] Open
Abstract
BACKGROUND The safety and efficacy of transarterial chemoembolization plus molecular targeted therapy (MTT) combined with immune checkpoint inhibitors (ICIs) in primary liver cancer have been demonstrated. However, the evidence for TACE plus MTT combined with ICIs in the treatment of recurrent hepatocellular carcinoma (RHCC) is limited. Given the excellent performance of this combination regimen in primary liver cancer, it is necessary to evaluate the efficacy of TACE plus MTT combined with ICIs in RHCC. METHODS A total of 88 patients with RHCC treated with TACE plus MTT combined with camrelizumab (TACE-TC group, n = 46) or TACE plus MTT (TACE-T group, n = 42) were retrospectively collected and analyzed. In this study, we evaluated the effectiveness and safety of combination therapy for patients with RHCC by analyzing tumor response, progression-free survival (PFS), overall survival (OS), laboratory biochemical indices, and adverse events (AEs). RESULTS TACE-TC was superior to TACE-T in PFS (14.0 vs. 8.9 months, p = 0.034) and OS (31.1 vs. 20.2 months, p = 0.009). Moreover, TACE-TC achieved more preferable benefits with respect to disease control rate (89.1% vs. 71.4%, p = 0.036) and objective response rate (47.8% vs. 26.2%, p = 0.036) compared with TACE-T in patients with RHCC. Compared with the TACE-T group, the AFP level in the TACE-TC group decreased more significantly after 3 months of treatment. Multivariate analysis showed that treatment option was a significant predictor of OS and PFS, while the portal vein tumor thrombus and interval of recurrence from initial treatment were another prognostic factor of PFS. There was no significant difference between the TACE-TC and TACE-T groups for Grade 3-4 adverse events. CONCLUSIONS A combination therapy of TACE, MTT, and camrelizumab significantly improved tumor response and prolonged survival duration, showing a better survival prognosis for RHCC patients.
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Affiliation(s)
- Changlong Hou
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China.
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China.
| | - Baizhu Xiong
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China
| | - Lei Zhou
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Yipeng Fei
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Changgao Shi
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Xianhai Zhu
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Tao Xie
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
| | - Yulin Wu
- Department of Intervention, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, 107# Huanhu East Road, Shushan District, 230031, Hefei, Anhui, People's Republic of China
- Graduate School of Bengbu Medical College, Bengbu, Anhui, China
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Ma H, Yan QZ, Ma JR, Li DF, Yang JL. Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies. World J Gastroenterol 2024; 30:1295-1312. [PMID: 38596493 PMCID: PMC11000084 DOI: 10.3748/wjg.v30.i10.1295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2023] [Revised: 12/25/2023] [Accepted: 01/24/2024] [Indexed: 03/14/2024] Open
Abstract
Hepatitis B virus (HBV) reactivation is a clinically significant challenge in disease management. This review explores the immunological mechanisms underlying HBV reactivation, emphasizing disease progression and management. It delves into host immune responses and reactivation's delicate balance, spanning innate and adaptive immunity. Viral factors' disruption of this balance, as are interactions between viral antigens, immune cells, cytokine networks, and immune checkpoint pathways, are examined. Notably, the roles of T cells, natural killer cells, and antigen-presenting cells are discussed, highlighting their influence on disease progression. HBV reactivation's impact on disease severity, hepatic flares, liver fibrosis progression, and hepatocellular carcinoma is detailed. Management strategies, including anti-viral and immunomodulatory approaches, are critically analyzed. The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation. In conclusion, this comprehensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation. With a dedicated focus on understanding its implications for disease progression and the prospects of efficient management strategies, this article contributes significantly to the knowledge base. The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches, ultimately enhancing disease management and elevating patient outcomes. The dynamic landscape of management strategies is critically scrutinized, spanning anti-viral and immunomodulatory approaches. The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
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Affiliation(s)
- Hui Ma
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Qing-Zhu Yan
- Department of Ultrasound Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Jing-Ru Ma
- Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Dong-Fu Li
- Digestive Diseases Center, Department of Hepatopancreatobiliary Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
| | - Jun-Ling Yang
- Department of Respiratory and Critical Care Medicine, The Second Hospital of Jilin University, Changchun 130000, Jilin Province, China
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Wang H, Liu L, Gong H, Li H. Upregulation of FAM134B inhibits endoplasmic reticulum stress-related degradation protein expression and promotes hepatocellular carcinogenesis. J Cell Mol Med 2024; 28:e17964. [PMID: 37728036 PMCID: PMC10902567 DOI: 10.1111/jcmm.17964] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Revised: 09/06/2023] [Accepted: 09/08/2023] [Indexed: 09/21/2023] Open
Abstract
Endoplasmic reticulum (ER) stress can stimulate the proliferation and metastasis of hepatocellular carcinoma (HCC) cells while hindering apoptosis and immune system function, but the molecular mechanism of ER stress in HCC has yet to be fully studied. We aim to investigate the molecular mechanism by which FAM134B inhibits autophagy of HCC cells by reducing the expression of ER stress-related degradation proteins. Clinical samples were collected for this study. Normal liver cell lines HL7702 and Hep3B and Huh7 HCC cell lines were cultured. Construction of FAM134B knockdown cell line. Cell proliferation was measured using the CCK-8 assay, while cell migration and invasion capabilities were detected using the plate colony formation assay. Flow cytometry was used to detect the apoptosis rate. Transmission electron microscopy was used to observe the formation of autophagosomes. qRT-PCR and WB detective expression changes related to autophagy proteins. Finally, the expression of the relevant proteins was observed by immunohistochemistry. The expression of FAM134B was significantly increased in human liver cancer tissue and HCC cell lines Hep3B and Huh7. After the lentiviral vector was transfected into Hep3B cells with sh-FAM134B, results showed that sh-FAM134B could effectively inhibit Hep3B cell proliferation and promote HCC cell apoptosis. Meanwhile, sh-FAM134B could effectively induce the autophagy of Hep3B liver cancer cells. Immunohistochemistry results showed that sh-FAM134B could effectively induce ER stress. FAM134B inhibits HCC cell autophagy and promotes the progression of liver cancer by inhibiting the expression of ER stress-related degradation factors such as DERL2, EDEM1, SEL1L and HRD1.
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Affiliation(s)
- Houhong Wang
- Department of General SurgeryThe Affiliated Bozhou Hospital of Anhui Medical UniversityBozhouChina
| | - Lu Liu
- Department of Endocrine DepartmentThe Affiliated Nantong Hospital of Shanghai Jiao Tong UniversityNantongChina
| | - Huihui Gong
- Faculty of Health and Life SciencesOxford Brookes UniversityOxfordEnglandUK
| | - Heng Li
- Department of Comprehensive Surgery, Anhui Provincial Cancer HospitalWest District of The First Affiliated Hospital of USTCHefeiChina
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Qin S, Pan H, Blanc JF, Grando V, Lim HY, Chang XY, O'Brate A, Stroh C, Friese-Hamim M, Albers J, Johne A, Faivre S. Activity of Tepotinib in Hepatocellular Carcinoma With High-Level MET Amplification: Preclinical and Clinical Evidence. JCO Precis Oncol 2024; 8:e2300328. [PMID: 38354329 DOI: 10.1200/po.23.00328] [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: 06/28/2023] [Revised: 09/29/2023] [Accepted: 12/11/2023] [Indexed: 02/16/2024] Open
Abstract
PURPOSE MET amplification (METamp) has been reported in 1%-5% of patients with hepatocellular carcinoma (HCC) and may be sensitive to MET inhibition. Tepotinib, a selective MET inhibitor, has shown promising activity in HCC with MET overexpression. We investigated the preclinical and clinical activity of tepotinib in HCC with METamp (MET gene copy number [GCN] ≥5), including high-level METamp (MET GCN ≥10). METHODS Preclinical antitumor activity of tepotinib 100 mg/kg (orally, days 1-5, every 7 days, 3-5 weeks; 3-12 replicates) was evaluated according to METamp status, as determined using the nCounter platform (NanoString), in 37 HCC patient-derived xenografts (PDXs) in immunodeficient mice. Clinical outcomes were evaluated in patients with METamp by fluorescence in situ hybridization who received tepotinib 500 mg (450 mg active moiety) in two phase Ib/II trials in HCC with MET overexpression. RESULTS Across the PDX models, tepotinib induced complete or near-complete tumor regression in the only two models with high-level METamp. Median tumor volume reductions were 100% and 99.8% in models with MET GCN 47.1 and 44.0, respectively. Across the two clinical trials, 15/121 patients had METamp. Disease control was achieved by 11/15 patients with METamp (complete response [CR], n = 1; partial response [PR], n = 4; stable disease [SD], n = 6) and 4/4 with high-level METamp (CR, n = 1; PR, n = 2; SD, n = 1). All three patients with high-level METamp and objective response received treatment for >1 year, including one patient who received first-line tepotinib for >6 years. CONCLUSION High-level METamp may be an oncogenic driver in HCC that is sensitive to MET inhibitors such as tepotinib.
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Affiliation(s)
- Shukui Qin
- PLA Cancer Center, Nanjing Bayi Hospital, Nanjing, China
- Cancer Center of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Hongming Pan
- Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | | | | | - Ho Yeong Lim
- Samsung Medical Center, Sungkyunkwan University, Seoul, Republic of Korea
| | - Xin Ying Chang
- Global Clinical Development China, Merck Serono Co., Ltd, Beijing, China, an affiliate of Merck KGaA, Darmstadt, Germany
| | - Aurora O'Brate
- The healthcare business of Merck KGaA, Darmstadt, Germany
| | | | | | - Joachim Albers
- The healthcare business of Merck KGaA, Darmstadt, Germany
| | - Andreas Johne
- The healthcare business of Merck KGaA, Darmstadt, Germany
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El-Nakeep S, Kasi A. Editorial: Hepatocellular carcinoma: from personalized medicine to practical guidelines. Front Pharmacol 2023; 14:1301202. [PMID: 38026990 PMCID: PMC10653316 DOI: 10.3389/fphar.2023.1301202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Accepted: 10/25/2023] [Indexed: 12/01/2023] Open
Affiliation(s)
- Sarah El-Nakeep
- Hepatogastroenterology Unit, Internal Medicine Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Anup Kasi
- Cancer Center, University of Kansas, Kansas City, MO, United States
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Zhang Y, Shen H, Zheng R, Sun Y, Xie X, Lu MD, Liu B, Huang G. Development and Assessment of Nomogram Based on AFP Response for Patients with Unresectable Hepatocellular Carcinoma Treated with Immune Checkpoint Inhibitors. Cancers (Basel) 2023; 15:5131. [PMID: 37958306 PMCID: PMC10647527 DOI: 10.3390/cancers15215131] [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: 08/09/2023] [Revised: 10/15/2023] [Accepted: 10/20/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Immune checkpoint inhibitors (ICIs) have been increasingly used to treat hepatocellular carcinoma (HCC). Prognostic biomarkers are an unmet need. We aimed to develop a prognostic nomogram for patients with unresectable HCC receiving ICIs therapy. METHODS A total of 120 patients with unresectable HCC receiving ICIs treatment were enrolled in this study. Patients were randomly divided into a training set (n = 84) and a validation set (n = 36) in a 7:3 ratio. Clinical characteristics were retrospectively analyzed. Serum α-fetoprotein protein (AFP) response was defined as a decline of ≥20% in AFP levels within the initial eight weeks of treatment. Univariable and multivariable Cox analyses were used to select relevant variables and construct the nomogram. The areas under the receiver operating characteristic curves (AUCs) were used to determine the performance of the model. Kaplan-Meier analysis with the log-rank test was used to compare different risk groups. RESULTS The median progression-free survival (PFS) was 7.7 months. In the multivariate Cox analysis, the presence of extrahepatic metastasis (hazard ratio [HR] = 2.08, 95% confidence interval [CI]: 1.02-4.27, p < 0.05), white blood cell count (HR = 3.48, 95% CI: 1.02-11.88, p < 0.05) and AFP response (HR = 0.41, 95% CI: 0.18-0.95, p < 0.05) independently predicted PFS. A nomogram for PFS was established with AUCs of 0.79 and 0.70 in the training and validation sets, respectively. The median PFS of the high- and low-risk subgroups was 3.5 and 11.7 months, respectively (p < 0.05). CONCLUSION The nomogram could predict PFS in patients with unresectable HCC receiving ICIs treatment and further help decision making in daily clinical practice.
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Affiliation(s)
- Yi Zhang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Hui Shen
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Ruiying Zheng
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Yueting Sun
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Xiaoyan Xie
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Ming-De Lu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China
| | - Baoxian Liu
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
| | - Guangliang Huang
- Division of Interventional Ultrasound, Department of Medical Ultrasonics, Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhong Shan Road 2, Guangzhou 510080, China; (Y.Z.); (H.S.); (M.-D.L.)
- Department of Medical Ultrasonics, Guangxi Hospital Division, The First Affiliated Hospital of Sun Yat-sen University, Nanning 530022, China
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11
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Feng Q, Huang Z, Song L, Wang L, Lu H, Wu L. Combining bulk and single-cell RNA-sequencing data to develop an NK cell-related prognostic signature for hepatocellular carcinoma based on an integrated machine learning framework. Eur J Med Res 2023; 28:306. [PMID: 37649103 PMCID: PMC10466881 DOI: 10.1186/s40001-023-01300-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2023] [Accepted: 08/18/2023] [Indexed: 09/01/2023] Open
Abstract
BACKGROUND The application of molecular targeting therapy and immunotherapy has notably prolonged the survival of patients with hepatocellular carcinoma (HCC). However, multidrug resistance and high molecular heterogeneity of HCC still prevent the further improvement of clinical benefits. Dysfunction of tumor-infiltrating natural killer (NK) cells was strongly related to HCC progression and survival benefits of HCC patients. Hence, an NK cell-related prognostic signature was built up to predict HCC patients' prognosis and immunotherapeutic response. METHODS NK cell markers were selected from scRNA-Seq data obtained from GSE162616 data set. A consensus machine learning framework including a total of 77 algorithms was developed to establish the gene signature in TCGA-LIHC data set, GSE14520 data set, GSE76427 data set and ICGC-LIRI-JP data set. Moreover, the predictive efficacy on ICI response was externally validated by GSE91061 data set and PRJEB23709 data set. RESULTS With the highest C-index among 77 algorithms, a 11-gene signature was established by the combination of LASSO and CoxBoost algorithm, which classified patients into high- and low-risk group. The prognostic signature displayed a good predictive performance for overall survival rate, moderate to high predictive accuracy and was an independent risk factor for HCC patients' prognosis in TCGA, GEO and ICGC cohorts. Compared with high-risk group, low-risk patients showed higher IPS-PD1 blocker, IPS-CTLA4 blocker, common immune checkpoints expression but lower TIDE score, which indicated low-risk patients might be prone to benefiting from ICI treatment. Moreover, a real-world cohort, PRJEB23709, also revealed better immunotherapeutic response in low-risk group. CONCLUSIONS Overall, the present study developed a gene signature based on NK cell-related genes, which offered a novel platform for prognosis and immunotherapeutic response evaluation of HCC patients.
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Affiliation(s)
- Qian Feng
- Department of Emergency, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
| | - Zhihao Huang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1st min de Road, Nanchang, 330000, China
| | - Lei Song
- Department of General Practice, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
| | - Le Wang
- Department of Blood Transfusion, The Second Affiliated Hospital of Nanchang University, Nanchang, 330000, China
| | - Hongcheng Lu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1st min de Road, Nanchang, 330000, China.
| | - Linquan Wu
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1st min de Road, Nanchang, 330000, China.
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12
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Lin PC, Hsu WY, Lee PY, Hsu SH, Chiou SS. Insights into Hepatocellular Carcinoma in Patients with Thalassemia: From Pathophysiology to Novel Therapies. Int J Mol Sci 2023; 24:12654. [PMID: 37628834 PMCID: PMC10454908 DOI: 10.3390/ijms241612654] [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: 06/26/2023] [Revised: 08/02/2023] [Accepted: 08/07/2023] [Indexed: 08/27/2023] Open
Abstract
Thalassemia is a heterogeneous congenital hemoglobinopathy common in the Mediterranean region, Middle East, Indian subcontinent, and Southeast Asia with increasing incidence in Northern Europe and North America due to immigration. Iron overloading is one of the major long-term complications in patients with thalassemia and can lead to organ damage and carcinogenesis. Hepatocellular carcinoma (HCC) is one of the most common malignancies in both transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The incidence of HCC in patients with thalassemia has increased over time, as better chelation therapy confers a sufficiently long lifespan for the development of HCC. The mechanisms of iron-overloading-associated HCC development include the increased reactive oxygen species (ROS), inflammation cytokines, dysregulated hepcidin, and ferroportin metabolism. The treatment of HCC in patients with thalassemia was basically similar to those in general population. However, due to the younger age of HCC onset in thalassemia, regular surveillance for HCC development is mandatory in TDT and NTDT. Other supplemental therapies and experiences of novel treatments for HCC in the thalassemia population were also reviewed in this article.
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Affiliation(s)
- Pei-Chin Lin
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (P.-C.L.); (W.-Y.H.); (P.-Y.L.)
- School of Post-Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Wan-Yi Hsu
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (P.-C.L.); (W.-Y.H.); (P.-Y.L.)
| | - Po-Yi Lee
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (P.-C.L.); (W.-Y.H.); (P.-Y.L.)
| | - Shih-Hsien Hsu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Center of Applied Genomics, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
| | - Shyh-Shin Chiou
- Division of Pediatric Hematology and Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan; (P.-C.L.); (W.-Y.H.); (P.-Y.L.)
- Center of Applied Genomics, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan
- Division of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807378, Taiwan
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13
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Loong HH, Shimizu T, Prawira A, Tan AC, Tran B, Day D, Tan DSP, Ting FIL, Chiu JW, Hui M, Wilson MK, Prasongsook N, Koyama T, Reungwetwattana T, Tan TJ, Heong V, Voon PJ, Park S, Tan IB, Chan SL, Tan DSW. Recommendations for the use of next-generation sequencing in patients with metastatic cancer in the Asia-Pacific region: a report from the APODDC working group. ESMO Open 2023; 8:101586. [PMID: 37356359 PMCID: PMC10319859 DOI: 10.1016/j.esmoop.2023.101586] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 03/27/2023] [Accepted: 05/18/2023] [Indexed: 06/27/2023] Open
Abstract
INTRODUCTION Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers. METHODS The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types [breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC)] were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration. RESULTS The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC. CONCLUSION This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.
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Affiliation(s)
- H H Loong
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
| | - T Shimizu
- Department of Pulmonary Medicine and Medical Oncology, Wakayama Medical University Graduate School of Medicine, Wakayama, Japan
| | - A Prawira
- Cancer Trials and Research Unit, Prince of Wales Hospital, Sydney, Australia
| | - A C Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - B Tran
- Department of Oncology, Peter MacCallum Cancer Centre, Melbourne
| | - D Day
- Department of Oncology, Monash Health and Monash University, Australia
| | - D S P Tan
- Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - F I L Ting
- Department of Medicine, Dr. Pablo O. Torre Memorial Hospital, Bacolod, Philippines
| | - J W Chiu
- Department of Medicine, The University of Hong Kong, HKSAR, Pok Fu Lam, Hong Kong, China
| | - M Hui
- Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown, Australia
| | - M K Wilson
- Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand
| | - N Prasongsook
- Division of Medical Oncology, Phramongkutklao Hospital, Bangkok, Thailand
| | - T Koyama
- Department of Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan
| | - T Reungwetwattana
- Division of Medical Oncology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - T J Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - V Heong
- Department Medical Oncology, Tan Tock Seng Hospital, Singapore
| | - P J Voon
- Radiotherapy and Oncology Department, Hospital Umum Sarawak, Kuching, Malaysia
| | - S Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - I B Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore
| | - S L Chan
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong, China
| | - D S W Tan
- Division of Medical Oncology, National Cancer Centre Singapore, Singapore.
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14
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Zhang J, Liu L, Wang Z, Hou M, Dong Z, Yu J, Sun R, Cui G. Ubiquitin-proteasome system-based signature to predict the prognosis and drug sensitivity of hepatocellular carcinoma. Front Pharmacol 2023; 14:1172908. [PMID: 37180696 PMCID: PMC10166894 DOI: 10.3389/fphar.2023.1172908] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Accepted: 04/17/2023] [Indexed: 05/16/2023] Open
Abstract
Background: Ubiquitin-proteasome system (UPS) is implicated in cancer occurrence and progression. Targeting UPS is emerging as a promising therapeutic target for cancer treatment. Nevertheless, the clinical significance of UPS in hepatocellular carcinoma (HCC) has not been entirely elucidated. Methods: Differentially expressed UPS genes (DEUPS) were screened from LIHC-TCGA datasets. The least absolute shrinkage and selection operator (LASSO) and stepwise multivariate regression analysis were conducted to establish a UPS-based prognostic risk model. The robustness of the risk model was further validated in HCCDB18, GSE14520, and GSE76427 cohorts. Subsequently, immune features, clinicopathologic characteristics, enrichment pathways, and anti-tumor drug sensitivity of the model were further evaluated. Moreover, a nomogram was established to improve the predictive ability of the risk model. Results: Seven UPS-based signatures (ATG10, FBXL7, IPP, MEX3A, SOCS2, TRIM54, and PSMD9) were developed for the prognostic risk model. Individuals with HCC with high-risk scores presented a more dismal prognosis than those with low-risk scores. Moreover, larger tumor size, advanced TNM stage, and tumor grade were observed in the high-risk group. Additionally, cell cycle, ubiquitin-mediated proteolysis, and DNA repair pathways were intimately linked to the risk score. In addition, obvious immune cell infiltration and sensitive drug response were identified in low-risk patients. Furthermore, both nomogram and risk score showed a significant prognosis-predictive ability. Conclusion: Overall, we established a novel UPS-based prognostic risk model in HCC. Our results will facilitate a deep understanding of the functional role of UPS-based signature in HCC and provide a reliable prediction of clinical outcomes and anti-tumor drug responses for patients with HCC.
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Affiliation(s)
- Jianxiang Zhang
- Department of General Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liwen Liu
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zenghan Wang
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Mingyang Hou
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Zihui Dong
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jia Yu
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Ranran Sun
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guangying Cui
- Precision Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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15
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Reflections on prediction of microvascular invasion in hepatocellular carcinoma by pathology images. Hepatol Int 2023; 17:514-515. [PMID: 36710301 DOI: 10.1007/s12072-022-10432-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Accepted: 09/25/2022] [Indexed: 01/31/2023]
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16
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Zhang Y, Pang S, Sun B, Zhang M, Jiao X, Lai L, Qian Y, Yang N, Yang W. ELOVLs Predict Distinct Prognosis Value and Immunotherapy Efficacy In Patients With Hepatocellular Carcinoma. Front Oncol 2022; 12:884066. [PMID: 35912257 PMCID: PMC9334671 DOI: 10.3389/fonc.2022.884066] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 06/17/2022] [Indexed: 11/13/2022] Open
Abstract
Background Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with high prevalence worldwide and poor prognosis. It has been verified that elongation of very-long-chain fatty acids gene family (ELOVLs), a group of genes that responsible for elongation of saturated and polyunsaturated fatty acids, participate in the pathogenesis and development of multiplex disease including cancers. However, the functions and prognosis of ELOVLs in HCC are still indistinguishable. Methods First, we searched the mRNA expression and survival data of ELOVLs in patients with HCC via the data of The Cancer Genome Atlas (TCGA). The prognosis value of ELOVLs on HCC was assessed by Kaplan–Meier plotter and Cox regression analysis. reverse transcription quantitative- polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry were applied to assess the specific mRNA and protein expression of ELOVLs in HCC clinical specimens of our cohort. Then, the functional enrichment of ELOVL1 especially the pathways relating to the immune was conducted utilizing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis. Additionally, TIMER, CIBERSOR, and tumor immune dysfunction and exclusion (TIDE) were employed to evaluate the relationship between ELOVL1 and immune responses. Last, the correlation of ELOVL1 with genome heterogeneity [microsatellite instability (MSI), tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), homologous recombination deficiency (HRD), purity, ploidy, loss of heterozygosity (LOH), and neoantigens] and mutational landscape were also evaluated basing on the date in TCGA. Results Significant expression alteration was observed in ELOVLs family at the pan-cancer level. In liver cancer, ELOVL1 and ELOVL3 were strongly associated with poor prognosis of HCC by survival analysis and differential expression analysis. Immunohistochemistry microarray, WB, and RT-qPCR confirmed that ELOVL1 but not ELOVL3 played an important role in HCC. Mechanistically, functional network analysis revealed that ELOVL1 might be involved in the immune response. ELOVL1 could affect immune cell infiltration and immune checkpoint markers such as PD-1 and CTLA4 in HCC. Meanwhile, high expression of ELOVL1 would be insensitive to immunotherapy. Correlation analysis of immunotherapy markers showed that ELOVL1 has been associated with MSI, TMB, and oncogene mutations such as TP53. Conclusion ELOVLs play distinct prognostic value in HCC. ELOVL1 could predict the poor prognosis and might be a potential indicator of immunotherapy efficacy in HCC patients.
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Affiliation(s)
- Yu Zhang
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Shujie Pang
- Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Bo Sun
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Minbo Zhang
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Xiaoxiao Jiao
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Linying Lai
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yiting Qian
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Ning Yang
- Department V of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
- *Correspondence: Ning Yang, ; Wenzhuo Yang,
| | - Wenzhuo Yang
- Department of Gastroenterology and Hepatology, Institute of Digestive Disease, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Ning Yang, ; Wenzhuo Yang,
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