Serpin family H member 1 and its related collagen gene network are the potential prognostic biomarkers and anticancer targets for glioma

被引:6
作者
Wang, Qi [1 ]
Wang, Zhe [1 ]
机构
[1] First Hosp Jilin Univ, Dept Geriatr, 71 Xinmin St, Changchun 130000, Jilin, Peoples R China
关键词
glioma; immune checkpoints; immune infiltration; immunotherapy; prognosis; HSP47; CANCER; CELLS; MACROPHAGES; SURVIVAL; GROWTH;
D O I
10.1002/jbt.23541
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
Serpin family H member 1 (SERPINH1) is responsible for encoding the protein known as heat shock protein 47, which functions as a molecular chaperone specific to collagen (COL). This protein has been identified as a potential therapeutic target for COL-related disorders. In this study, we aimed to investigate the role of SERPINH1 in the tumorigenicity of gliomas. To achieve this, we utilized various bioinformatics tools to analyze gene expression, overall survival, protein-protein interactions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and Gene Set Enrichment Analysis (GSEA). Based on The Cancer Genome Atlas database revealed that SERPINH1 and four COL family members (COL1A1, COL3A1, COL4A1, and COL4A2) expression are significantly upregulated in glioma tissues compared with normal nontumor tissues. GO, KEGG, and GSEA analyses exhibited that SERPINH1 is implicated in the establishment and degradation of COL-containing extracellular matrix (ECM), focal adhesion, and ECM-receptor interaction in glioma. SERPINH1 is an independent prognostic factor, exhibiting a positive association with the augmentation of neutrophils and macrophages, as well as the manifestation of immune checkpoint molecules within glioma. Experimental assessments conducted both in vitro and in vivo demonstrated that the suppression of SERPINH1 impeded the migratory, invasive, and proliferative capacities of glioma cells, while concurrently fostering cellular apoptosis. Consequently, SERPINH1 emerges as an oncogenic gene and an independent prognostic marker for glioma, potentially facilitating the advancement of immunotherapeutic interventions for the treatment of glioma.
引用
收藏
页数:16
相关论文
共 45 条
[1]   Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer [J].
Bindea, Gabriela ;
Mlecnik, Bernhard ;
Tosolini, Marie ;
Kirilovsky, Amos ;
Waldner, Maximilian ;
Obenauf, Anna C. ;
Angell, Helen ;
Fredriksen, Tessa ;
Lafontaine, Lucie ;
Berger, Anne ;
Bruneval, Patrick ;
Fridman, Wolf Herman ;
Becker, Christoph ;
Pages, Franck ;
Speicher, Michael R. ;
Trajanoski, Zlatko ;
Galon, Jerome .
IMMUNITY, 2013, 39 (04) :782-795
[2]   The brain tumor microenvironment (vol 59, pg 1169, 2011) [J].
Charles, Nikki A. ;
Holland, Eric C. ;
Gilbertson, Richard ;
Glass, Rainer ;
Kettenmann, Helmut .
GLIA, 2012, 60 (03) :502-514
[3]   Hacking macrophage-associated immunosuppression for regulating glioblastoma angiogenesis [J].
Cui, Xin ;
Morales, Renee-Tyler Tan ;
Qian, Weiyi ;
Wang, Haoyu ;
Gagner, Jean-Pierre ;
Dolgalev, Igor ;
Placantonakis, Dimitris ;
Zagzag, David ;
Cimmino, Luisa ;
Snuderl, Matija ;
Lam, Raymond H. W. ;
Chen, Weiqiang .
BIOMATERIALS, 2018, 161 :164-178
[4]   BMP4 promotes hepatocellular carcinoma proliferation by autophagy activation through JNK1-mediated Bcl-2 phosphorylation [J].
Deng, Ganlu ;
Zeng, Shan ;
Qu, Yanling ;
Luo, Qingqing ;
Guo, Cao ;
Yin, Ling ;
Han, Ying ;
Li, Yiyi ;
Cai, Changjing ;
Fu, Yaojie ;
Shen, Hong .
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 2018, 37
[5]   The heat shock protein 47 as a potential biomarker and a therapeutic agent in cancer research [J].
Duarte, Beatriz Dal Pont ;
Bonatto, Diego .
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, 2018, 144 (12) :2319-2328
[6]   Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models [J].
Genoud, Vassilis ;
Marinari, Eliana ;
Nikolaev, Sergey I. ;
Castle, John C. ;
Bukur, Valesca ;
Dietrich, Pierre-Yves ;
Okada, Hideho ;
Walker, Paul R. .
ONCOIMMUNOLOGY, 2018, 7 (12)
[7]   Predictive biomarkers for checkpoint inhibitor-based immunotherapy [J].
Gibney, Geoffrey T. ;
Weiner, Louis M. ;
Atkins, Michael B. .
LANCET ONCOLOGY, 2016, 17 (12) :E542-E551
[8]   Immune microenvironment of gliomas [J].
Gieryng, Anna ;
Pszczolkowska, Dominika ;
Walentynowicz, Kacper A. ;
Rajan, Wenson D. ;
Kaminska, Bozena .
LABORATORY INVESTIGATION, 2017, 97 (05) :498-518
[9]   GSVA: gene set variation analysis for microarray and RNA-Seq data [J].
Haenzelmann, Sonja ;
Castelo, Robert ;
Guinney, Justin .
BMC BIOINFORMATICS, 2013, 14
[10]   The role of microglia and macrophages in glioma maintenance and progression [J].
Hambardzumyan, Dolores ;
Gutmann, David H. ;
Kettenmann, Helmut .
NATURE NEUROSCIENCE, 2016, 19 (01) :20-27