Proto-Oncogene FAM50A Can Regulate the Immune Microenvironment and Development of Hepatocellular Carcinoma In Vitro and In Vivo

被引:6
作者
Xie, Xudong [1 ]
Li, Li [1 ]
Tao, Shuai [2 ]
Chen, Mingsheng [3 ]
Fei, Ling [1 ]
Yang, Qunling [1 ]
Huang, Chenlu [1 ]
Chen, Liang [1 ]
机构
[1] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Liver Dis Dept, Shanghai 201508, Peoples R China
[2] Fudan Univ, Shanghai Publ Hlth Clin Ctr, Res Unit, Shanghai 201508, Peoples R China
[3] Fudan Univ, Res Ctr Biomat, Shanghai Publ Hlth Clin Ctr, Shanghai 201508, Peoples R China
关键词
hepatocellular carcinoma; FAM50A; prognostic value; immune cell infiltration; stemness degree; epithelial-mesenchymal transition; cell cycle; apoptosis; malignancy; xenotransplanted tumor; 1ST-LINE TREATMENT; OPEN-LABEL; SORAFENIB; CHEMOTHERAPY; BEVACIZUMAB; EXPRESSION; NIVOLUMAB; SURVIVAL; PLUS;
D O I
10.3390/ijms24043217
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hepatocellular carcinoma (HCC) is a vital global health problem. The characteristics are high morbidity, high mortality, difficulty in early diagnosis and insensitivity to chemotherapy. The main therapeutic schemes for treating HCC mainly include Tyrosine kinase inhibitors represented by sorafenib and lenvatinib. In recent years, immunotherapy for HCC has also achieved certain results. However, a great number of patients failed to benefit from systemic therapies. FAM50A belongs to the FAM50 family and can be used as a DNA-binding protein or transcription factor. It may take part in the splicing of RNA precursors. In studies of cancer, FAM50A has been demonstrated to participate in the progression of myeloid breast cancer and chronic lymphocytic leukemia. However, the effect of FAM50A on HCC is still unknown. In this study, we have demonstrated the cancer-promoting effects and diagnostic value of FAM50A in HCC using multiple databases and surgical samples. We identified the role of FAM50A in the tumor immune microenvironment (TIME) and immunotherapy efficacy in HCC. We also proved the effects of FAM50A on the malignancy of HCC in vitro and in vivo. In conclusion, we confirmed that FAM50A is an important proto-oncogene in HCC. FAM50A acts as a diagnostic marker, immunomodulator and therapeutic target for HCC.
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页数:19
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共 43 条
[1]  
Abbafati C, 2020, LANCET, V396, P1204
[2]   A Quantitative Analysis of Subclonal and Clonal Gene Mutations before and after Therapy in Chronic Lymphocytic Leukemia [J].
Amin, Nisar A. ;
Seymour, Erlene ;
Saiya-Cork, Kamlai ;
Parkin, Brian ;
Shedden, Kerby ;
Malek, Sami N. .
CLINICAL CANCER RESEARCH, 2016, 22 (17) :4525-4535
[3]   GALAD Score Detects Early Hepatocellular Carcinoma in an International Cohort of Patients With Nonalcoholic Steatohepatitis [J].
Best, Jan ;
Bechmann, Lars P. ;
Sowa, Jan-Peter ;
Sydor, Svenja ;
Dechene, Alexander ;
Pflanz, Kristina ;
Bedreli, Sotiria ;
Schotten, Clemens ;
Geier, Andreas ;
Berg, Thomas ;
Fischer, Janett ;
Vogel, Arndt ;
Bantel, Heike ;
Weinmann, Arndt ;
Schattenberg, Joern M. ;
Huber, Yvonne ;
Wege, Henning ;
von Felden, Johann ;
Schulze, Kornelius ;
Bettinger, Dominik ;
Thimme, Robert ;
Sinner, Friedrich ;
Schuette, Kerstin ;
Weiss, Karl Heinz ;
Toyoda, Hidenori ;
Yasuda, Satoshi ;
Kumada, Takashi ;
Berhane, Sarah ;
Wichert, Marc ;
Heider, Dominik ;
Gerken, Guido ;
Johnson, Philip ;
Canbay, Ali .
CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2020, 18 (03) :728-+
[4]   FDA Approval Summary: Atezolizumab Plus Bevacizumab for the Treatment of Patients with Advanced Unresectable or Metastatic Hepatocellular Carcinoma [J].
Casak, Sandra J. ;
Donoghue, Martha ;
Fashoyin-Aje, Lola ;
Jiang, Xiaoping ;
Rodriguez, Lisa ;
Shen, Yuan-Li ;
Xu, Yuan ;
Jiang, Xiling ;
Liu, Jiang ;
Zhao, Hong ;
Pierce, William F. ;
Mehta, Shubhangi ;
Goldberg, Kirsten B. ;
Theoret, Marc R. ;
Kluetz, Paul G. ;
Pazdur, Richard ;
Lemery, Steven J. .
CLINICAL CANCER RESEARCH, 2021, 27 (07) :1836-1841
[5]   Elevated Expression of PDZD11 Is Associated With Poor Prognosis and Immune Infiltrates in Hepatocellular Carcinoma [J].
Chen, Yao ;
Xie, Haifeng ;
Xie, Ting ;
Yang, Xunjun ;
Pang, Yilin ;
Ye, SongDao .
FRONTIERS IN GENETICS, 2021, 12
[6]   CRISPR screens uncover protective effect of PSTK as a regulator of chemotherapy-induced ferroptosis in hepatocellular carcinoma [J].
Chen, Yiran ;
Li, Li ;
Lan, Jie ;
Cui, Yang ;
Rao, Xiaosong ;
Zhao, Jing ;
Xing, Tao ;
Ju, Gaoda ;
Song, Guangtao ;
Lou, Jizhong ;
Liang, Jun .
MOLECULAR CANCER, 2022, 21 (01)
[7]   Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial [J].
Cheng, Ann-Lii ;
Kang, Yoon-Koo ;
Chen, Zhendong ;
Tsao, Chao-Jung ;
Qin, Shukui ;
Kim, Jun Suk ;
Luo, Rongcheng ;
Feng, Jifeng ;
Ye, Shenglong ;
Yang, Tsai-Sheng ;
Xu, Jianming ;
Sun, Yan ;
Liang, Houjie ;
Liu, Jiwei ;
Wang, Jiejun ;
Tak, Won Young ;
Pan, Hongming ;
Burock, Karin ;
Zou, Jessie ;
Voliotis, Dimitris ;
Guan, Zhongzhen .
LANCET ONCOLOGY, 2009, 10 (01) :25-34
[8]   Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection [J].
Feld, J. J. ;
Jacobson, I. M. ;
Hezode, C. ;
Asselah, T. ;
Ruane, P. J. ;
Gruener, N. ;
Abergel, A. ;
Mangia, A. ;
Lai, C. -L. ;
Chan, H. L. Y. ;
Mazzotta, F. ;
Moreno, C. ;
Yoshida, E. ;
Shafran, S. D. ;
Towner, W. J. ;
Tran, T. T. ;
McNally, J. ;
Osinusi, A. ;
Svarovskaia, E. ;
Zhu, Y. ;
Brainard, D. M. ;
McHutchison, J. G. ;
Agarwal, K. ;
Zeuzem, S. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (27) :2599-2607
[9]   Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma [J].
Finn, Richard S. ;
Qin, Shukui ;
Ikeda, Masafumi ;
Galle, Peter R. ;
Ducreux, Michel ;
Kim, Tae-You ;
Kudo, Masatoshi ;
Breder, Valeriy ;
Merle, Philippe ;
Kaseb, Ahmed O. ;
Li, Daneng ;
Verret, Wendy ;
Xu, Derek-Zhen ;
Hernandez, Sairy ;
Liu, Juan ;
Huang, Chen ;
Mulla, Sohail ;
Wang, Yulei ;
Lim, Ho Yeong ;
Zhu, Andrew X. ;
Cheng, Ann-Lii .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (20) :1894-1905
[10]   Global epidemiology of NAFLD-related HCC: trends, predictions, risk factors and prevention [J].
Huang, Daniel Q. ;
El-Serag, Hashem B. ;
Loomba, Rohit .
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2021, 18 (04) :223-238