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3. Re-Recognizing the Cellular Origin of the Primary Epithelial Tumors of the Liver

Author

Feng,Jiliang, Zhu,Ruidong, Yin,Yu, Wang,Shanshan, Zhou,Lei, Lv,Fudong, and Zhao,Dawei

Subjects
Journal of Hepatocellular Carcinoma
Abstract

Jiliang Feng,1 Ruidong Zhu,2 Yu Yin,3 Shanshan Wang,1 Lei Zhou,4 Fudong Lv,1 Dawei Zhao5 1Clinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2General Surgical Center, Beijing You-An Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 3Department of Pathology, Anhui Medical University, Hefei, 230032, People’s Republic of China; 4Department of Pathology, First Affiliated Hospital of Bengbu Medical College/Bengbu Medical College, Bengbu, 233004, People’s Republic of China; 5Department of Medical Imaging, Capital Medical University, Beijing, 100069, People’s Republic of ChinaCorrespondence: Jiliang FengClinical-Pathology Center, Beijing You-An Hospital, Capital Medical University, No. 8, Xitoutiao, Youanmenwai Street, FengTai District, Beijing, 100069, People’s Republic of ChinaTel +86-10-83997342Fax +86-10-83997343Email jiliangfeng@ccmu.edu.cnAbstract: The primary epithelial tumors of the liver (PETL) are composed of a series of heterogeneous tumors. Although the classification of PETLs has been updated several times by the World Health Organization, the cellular origins of some tumors in this family remain to be precisely depicted. In addition, certain tumors in different categories have similar histology, molecular phenotypes and biological characteristics, suggesting that they may have the same cellular origin. In this work, a narrative review method was adopted to review the relevant papers. By comparing the expression profiles of biomarkers of liver epithelium at different lineages and stages of differentiation, the cells-of-origin of some major members of the PETL family were reassessed. We propose that 1) hepatic adenomas, hepatocellular carcinomas (HCCs) and pure fetal hepatoblastomas (HBs) share the same spectrum in their cellular origin including the hepatocytic-committed progenitors (HCP) and their differentiated descendants. 2) Bile duct adenomas, peribiliary cysts and intrahepatic cholangiocellular carcinomas (ICCs) can share the same spectrum in their cellular origin including the cholangiocytic-committed progenitors (CCP) and their differentiated descendants. 3) The cells-of-origin of embryonal HBs include liver stem cells (LSCs), hepatoblasts, and transitional cells between them. Embryonal HB with small cell element, small cell undifferentiated HB and small cell neuroendocrine carcinoma of the liver can have the same or similar cells-of-origin from LSC. Embryonal HB lacking the small cell component of the LSC phenotype and presenting both hepatocytic and bile duct/ductule components may originate from actual hepatoblasts/hepatic progenitor cells (HPCs) as the combined HCC-ICC does. 4) Teratoid hepatoblastoma and mixed epithelial/mesenchymal HBs can be derived from the LSCs or even less committed extrahepatic pluripotent stem cell. 5) Many members of the PETLs family, including those derived from LSCs, hepatoblasts/HPCs, early HCPs and CCPs, have neuroendocrine potentiality. Except for those primary hepatic neuroendocrine tumor (PHNET) exhibit hepatocytic and/or cholangiocytic phenotypes, other PHNETs subtype may be derived from the descendants of LSC that differentiate towards the upper digestive tract, pancreas or other lineages.Keywords: HCC, tumor-initiating cell, hepatic progenitor, neuroendocrine tumors, hepatoblastoma

Published
2021

8. Generation of antibodies against COVID-19 virus for development of diagnostic tools

Author

Li, Maohua, primary, Jin, Ronghua, additional, Peng, Ya, additional, Wang, Cuiyan, additional, Ren, Wenlin, additional, Lv, Fudong, additional, Gong, Sitao, additional, Fang, Feng, additional, Wang, Qianyun, additional, Li, Jianli, additional, Shen, Tong, additional, Sun, Hunter, additional, Zhou, Lei, additional, Cui, Yali, additional, Song, Hao, additional, and Sun, Le, additional

Published
2020
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9. SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Author

Yang, Penghui, Huang, Xuanlin, Lai, Chengcai, Li, Lin, Li, Tieling, Huang, Peide, Ouyang, Songying, Yan, Jin, Cheng, Sijie, Lei, Guanglin, Wang, Zhaohai, Yu, Linxiang, Hong, Zhixian, Li, Ruisheng, Dong, Hui, Wang, Cheng, Yu, Yinghao, Wang, Xuan, Li, Xianghong, Wang, Liming, Lv, Fudong, Yin, Ye, Yang, Huanming, Song, Jianxun, Gao, Qiang, Wang, Xiliang, Zhang, Shaogeng, Yang, Penghui, Huang, Xuanlin, Lai, Chengcai, Li, Lin, Li, Tieling, Huang, Peide, Ouyang, Songying, Yan, Jin, Cheng, Sijie, Lei, Guanglin, Wang, Zhaohai, Yu, Linxiang, Hong, Zhixian, Li, Ruisheng, Dong, Hui, Wang, Cheng, Yu, Yinghao, Wang, Xuan, Li, Xianghong, Wang, Liming, Lv, Fudong, Yin, Ye, Yang, Huanming, Song, Jianxun, Gao, Qiang, Wang, Xiliang, and Zhang, Shaogeng

Abstract

Primary hepatic neuroendocrine tumors (PHNETs) are extremely rare NETs originating from the liver. These tumors are associated with heterogeneous prognosis, and few treatment targets for PHNETs have been identified. Because the major genetic alterations in PHNET are still largely unknown, we performed whole-exome sequencing of 22 paired tissues from PHNET patients and identified 22 recurring mutations of somatic genes involved in the following activities: epigenetic modification (BPTF, MECP2 and WDR5), cell cycle (TP53, ATM, MED12, DIDO1 and ATAD5) and neural development (UBR4, MEN1, GLUL and GIGYF2). Here, we show that TP53 and the SET domain containing the 1B gene (SETD1B) are the most frequently mutated genes in this set of samples (3/22 subjects, 13.6%). A biological analysis suggests that one of the three SETD1B mutants, A1054del, promotes cell proliferation, migration and invasion compared to wild-type SETD1B. Our work unveils that SETD1B A1054del mutant is functional in PHNET and implicates genes including TP53 in the disease. Our findings thus characterize the mutational landscapes of PHNET and implicate novel gene mutations linked to PHNET pathogenesis and potential therapeutic targets.

Published
2019

10. SET domain containing 1B gene is mutated in primary hepatic neuroendocrine tumors

Author

Yang, Penghui, primary, Huang, Xuanlin, additional, Lai, Chengcai, additional, Li, Lin, additional, Li, Tieling, additional, Huang, Peide, additional, Ouyang, Songying, additional, Yan, Jin, additional, Cheng, Sijie, additional, Lei, Guanglin, additional, Wang, Zhaohai, additional, Yu, Linxiang, additional, Hong, Zhixian, additional, Li, Ruisheng, additional, Dong, Hui, additional, Wang, Cheng, additional, Yu, Yinghao, additional, Wang, Xuan, additional, Li, Xianghong, additional, Wang, Liming, additional, Lv, Fudong, additional, Yin, Ye, additional, Yang, Huanming, additional, Song, Jianxun, additional, Gao, Qiang, additional, Wang, Xiliang, additional, and Zhang, Shaogeng, additional

Published
2019
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11. Early steep decline of liver stiffness predicts histological reversal of fibrosis in chronic hepatitis B patients treated with entecavir

Author

Kong, Yuanyuan, primary, Sun, Yameng, additional, Zhou, Jialing, additional, Wu, Xiaoning, additional, Chen, Yongpeng, additional, Piao, Hongxin, additional, Lu, Lungen, additional, Ding, Huiguo, additional, Nan, Yuemin, additional, Jiang, Wei, additional, Xu, Youqing, additional, Xie, Wen, additional, Li, Hanwei, additional, Feng, Bo, additional, Shi, Guangfeng, additional, Chen, Guofeng, additional, Li, Hai, additional, Zheng, Huanwei, additional, Cheng, Jilin, additional, Wang, Tailing, additional, Liu, Hui, additional, Lv, Fudong, additional, Shao, Chen, additional, Mao, Yimin, additional, Sun, Jihong, additional, Chen, Tao, additional, Han, Tao, additional, Han, Ying, additional, Wang, Lin, additional, Ou, Xiaojuan, additional, Zhang, Hui, additional, Jia, Jidong, additional, and You, Hong, additional

Published
2019
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13. Double-Dose Adenovirus-Mediated Adjuvant Gene Therapy Improves Liver Transplantation Outcomes in Patients with Advanced Hepatocellular Carcinoma

Author

Zhu, Ruidong, primary, Weng, Danhui, additional, Lu, Shichun, additional, Lin, Dongdong, additional, Wang, Menglong, additional, Chen, Dongdong, additional, Lv, Jun, additional, Li, Hongjun, additional, Lv, Fudong, additional, Xi, Ling, additional, Zhou, Jianfeng, additional, Ma, Ding, additional, and Li, Ning, additional

Published
2018
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14. The significance of glypican-3 expression profiling in the tumor cellular origin theoretical system for hepatocellular carcinoma progression

Author

Xue, Ran, primary, Feng, Jiliang, additional, Meng, Qinghua, additional, Lv, Fudong, additional, Zhu, Yueke, additional, Yu, Hongwei, additional, Zhang, Shijie, additional, Song, Chenzhao, additional, Sun, Lin, additional, Yue, Zhujun, additional, Feng, Shuai, additional, Che, Ruiwen, additional, Xiang, Qian, additional, and Jing, Xiaodan, additional

Published
2017
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15. New classification of liver biopsy assessment for fibrosis in chronic hepatitis B patients before and after treatment

Author

Sun, Yameng, primary, Zhou, Jialing, additional, Wang, Lin, additional, Wu, Xiaoning, additional, Chen, Yongpeng, additional, Piao, Hongxin, additional, Lu, Lungen, additional, Jiang, Wei, additional, Xu, Youqing, additional, Feng, Bo, additional, Nan, Yuemin, additional, Xie, Wen, additional, Chen, Guofeng, additional, Zheng, Huanwei, additional, Li, Hai, additional, Ding, Huiguo, additional, Liu, Hui, additional, Lv, Fudong, additional, Shao, Chen, additional, Wang, Tailing, additional, Ou, Xiaojuan, additional, Wang, Bingqiong, additional, Chen, Shuyan, additional, Wee, Aileen, additional, Theise, Neil D., additional, You, Hong, additional, and Jia, Jidong, additional

Published
2017
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20. Radiofrequency ablation plays double role in immunosuppression and activation of PBMCs in recurrent hepatocellular carcinoma.

Author

Zhao Y, Yang T, Ouyang Y, Rao W, Liu K, Zheng J, Lv F, Shi Y, Wang F, Liu D, Qiao L, Xia Z, Zhang Y, Chen D, and Wang W

Subjects
Humans, Leukocytes, Mononuclear, Vascular Endothelial Growth Factor A, Immunosuppression Therapy, Tumor Microenvironment, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Catheter Ablation, Radiofrequency Ablation
Abstract

Background: Radiofrequency ablation (RFA) is the primary curative treatment for hepatocellular carcinoma (HCC) patients who are not eligible for surgery. However, the effects of RFA on the global tumor immune response remain unclear., Method: In this study, we examined the phenotypic and functional changes in peripheral blood mononuclear cells (PBMCs) from recurrent HCC patients who had undergone two RFA treatments using mass cytometry and high-throughput mRNA assays., Results: We observed significant increase in monocytes and decrease in T cell subpopulations three days after the first RFA treatment and three days after the second RFA treatment. The down-regulation of GZMB, GZMH, GZMK, and CD8A, which are involved in the cytotoxic function of T cells, was observed following RFA. Furthermore, the population of CD8 effector and memory T cells (CD8 Teff and CD8 Tem) significantly decreased after RFA. The expression of CD5 and CD161 in various T cell subpopulations also showed significant reductions. Additionally, elevated secretion of VEGF was observed in monocytes, B cells, regulatory T cells (Tregs), and CD4 naive T cells., Conclusion: In recurrent HCC patients, serum components derived from radiofrequency therapy can enhance the antigen-presenting capacity of monocytes. However, they also inhibit the anti-cancer immune response by reducing the population of CD8 effector and memory T cells and suppressing the activation of T cells, as well as down-regulating the expression of CD161 and CD5 in various T cell subpopulations. These tumor-derived components also contribute to an immunosuppressive microenvironment by promoting the secretion of VEGF in monocytes, Tregs, B cells, and CD4 naive T cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Yang, Ouyang, Rao, Liu, Zheng, Lv, Shi, Wang, Liu, Qiao, Xia, Zhang, Chen and Wang.)

Published
2024
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