Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA

被引:9
作者
Sun, Weijie [1 ,2 ]
Wang, Jue [1 ]
Wang, Zhiqiang [1 ]
Xu, Ming [1 ]
Lin, Quanjun [1 ]
Sun, Peng [1 ]
Yuan, Yihang [1 ]
机构
[1] Shanghai Jiao Tong Univ, Tongren Hosp, Sch Med, Dept Gen Surg, Shanghai, Peoples R China
[2] Anhui Med Univ, Affiliated Hosp 1, Dept Infect Dis, Hefei, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
基金
中国国家自然科学基金;
关键词
hepatocellular carcinoma; basement membranes; prognosis; immunotherapy; machine learning; ScRNA-seq; CTSA; vitro experiment;
D O I
10.3389/fimmu.2023.1185916
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Hepatocellular carcinoma (HCC) is a malignant tumor with high recurrence and metastasis rates and poor prognosis. Basement membrane is a ubiquitous extracellular matrix and is a key physical factor in cancer metastasis. Therefore, basement membrane-related genes may be new targets for the diagnosis and treatment of HCC. We systematically analyzed the expression pattern and prognostic value of basement membrane-related genes in HCC using the TCGA-HCC dataset, and constructed a new BMRGI based on WGCNA and machine learning. We used the HCC single-cell RNA-sequencing data in GSE146115 to describe the single-cell map of HCC, analyzed the interaction between different cell types, and explored the expression of model genes in different cell types. BMRGI can accurately predict the prognosis of HCC patients and was validated in the ICGC cohort. In addition, we also explored the underlying molecular mechanisms and tumor immune infiltration in different BMRGI subgroups, and confirmed the differences in response to immunotherapy in different BMRGI subgroups based on the TIDE algorithm. Then, we assessed the sensitivity of HCC patients to common drugs. In conclusion, our study provides a theoretical basis for the selection of immunotherapy and sensitive drugs in HCC patients. Finally, we also considered CTSA as the most critical basement membrane-related gene affecting HCC progression. In vitro experiments showed that the proliferation, migration and invasion abilities of HCC cells were significantly impaired when CTSA was knocked down.
引用
收藏
页数:14
相关论文
共 43 条
  • [21] RNA Helicase DDX24 Stabilizes LAMB1 to Promote Hepatocellular Carcinoma Progression
    Liu, Tianze
    Gan, Hairun
    He, Simeng
    Deng, Jia
    Hu, Xinyan
    Li, Luting
    Cai, Li
    He, Jianzhong
    Long, Haoyu
    Cai, Jianxun
    Li, Hanjie
    Zhang, Qianqian
    Wang, Lijie
    Chen, Fangbin
    Chen, Yuming
    Zhang, Haopei
    Li, Jian
    Yang, Lukun
    Liu, Ye
    Yang, Jian-Hua
    Kuang, Dong-Ming
    Pang, Pengfei
    He, Huanhua
    Shan, Hong
    [J]. CANCER RESEARCH, 2022, 82 (17) : 3074 - 3087
  • [22] Hepatocellular carcinoma
    Llovet, Josep M.
    Kelley, Robin Kate
    Villanueva, Augusto
    Singal, Amit G.
    Pikarsky, Eli
    Roayaie, Sasan
    Lencioni, Riccardo
    Koike, Kazuhiko
    Zucman-Rossi, Jessica
    Finn, Richard S.
    [J]. NATURE REVIEWS DISEASE PRIMERS, 2021, 7 (01)
  • [23] Development and validation of a TP53-associated immune prognostic model for hepatocellular carcinoma
    Long, Junyu
    Wang, Anqiang
    Bai, Yi
    Lin, Jianzhen
    Yang, Xu
    Wang, Dongxu
    Yang, Xiaobo
    Jiang, Yan
    Zhao, Haitao
    [J]. EBIOMEDICINE, 2019, 42 : 363 - 374
  • [24] HLA-G Neo-Expression on Tumors
    Loustau, Maria
    Anna, Francois
    Drean, Raphaelle
    Lecomte, Martin
    Langlade-Demoyen, Pierre
    Caumartin, Julien
    [J]. FRONTIERS IN IMMUNOLOGY, 2020, 11
  • [25] Identification and analysis of necroptosis-associated signatures for prognostic and immune microenvironment evaluation in hepatocellular carcinoma
    Lu, Juan
    Yu, Chengbo
    Bao, Qiongling
    Zhang, Xiaoqian
    Wang, Jie
    [J]. FRONTIERS IN IMMUNOLOGY, 2022, 13
  • [26] oncoPredict: an R package for predicting in vivo or cancer patient drug response and biomarkers from cell line screening data
    Maeser, Danielle
    Gruener, Robert F.
    Huang, Rong Stephanie
    [J]. BRIEFINGS IN BIOINFORMATICS, 2021, 22 (06)
  • [27] The matrix environmental and cell mechanical properties regulate cell migration and contribute to the invasive phenotype of cancer cells
    Mierke, Claudia Tanja
    [J]. REPORTS ON PROGRESS IN PHYSICS, 2019, 82 (06)
  • [28] Endothelial Basement Membrane Components and Their Products, Matrikines: Active Drivers of Pulmonary Hypertension?
    Mutgan, Ayse Ceren
    Jandl, Katharina
    Kwapiszewska, Grazyna
    [J]. CELLS, 2020, 9 (09)
  • [29] Extracellular matrix (ECM) stiffness and degradation as cancer drivers
    Najafi, Masoud
    Farhood, Bagher
    Mortezaee, Keywan
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2019, 120 (03) : 2782 - 2790
  • [30] Basement membrane stiffness determines metastases formation
    Reuten, Raphael
    Zendehroud, Sina
    Nicolau, Monica
    Fleischhauer, Lutz
    Laitala, Anu
    Kiderlen, Stefanie
    Nikodemus, Denise
    Wullkopf, Lena
    Nielsen, Sebastian Rune
    McNeilly, Sarah
    Prein, Carina
    Rafaeva, Maria
    Schoof, Erwin M.
    Furtwangler, Benjamin
    Porse, Bo T.
    Kim, Hyobin
    Won, Kyoung Jae
    Sudhop, Stefanie
    Zornhagen, Kamilla Westarp
    Suhr, Frank
    Maniati, Eleni
    Pearce, Oliver M. T.
    Koch, Manuel
    Oddershede, Lene Broeng
    Van Agtmael, Tom
    Madsen, Chris D.
    Mayorca-Guiliani, Alejandro E.
    Bloch, Wilhelm
    Netz, Roland R.
    Clausen-Schaumann, Hauke
    Erler, Janine T.
    [J]. NATURE MATERIALS, 2021, 20 (06) : 892 - +