Cathepsin A upregulation in glioma: a potential therapeutic target associated with immune infiltration
CTSA in glioma
Abstract
Backgrounds: Glioma is the result of malignant transformation of glial cells in the white matter of the brain or spinal cord and accounts for approximately 80% of all intracranial malignancies. Cathepsin A (CTSA) is highly expressed in a variety of tumor tissues, but its role in glioma is poorly studied. This study analyses the relationship between CTSA, and glioma based on TCGA
Methods: Data for glioma patients were collected from TCGA and the expression level of CTSA was compared between paired glioma tissues and normal tissues with Wilcoxon rank-sum test. In addition, the Wilcoxon rank-sum test was also applied to analyze the relationship between clinicopathologic features and CTSA expression. Kaplan-Meier Plotter was applied to analyze OS, DSS and PFI. Immuno-infiltration analysis of BLCA was performed by single sample gene set enrichment analysis (ssGSEA) in the "GSVA" R package.
Results: The CTSA was overexpressed in glioma tissues compared to normal tissues (P<0.001). The high expression of CTSA was significantly related to 1p/19q codeletion, IDH, WHO grade and histological type. Kaplan-Meier survival analysis showed that patients with glioma characterized with high expressed CTSA had a poorer OS (HR=2.16 P<0.001), DSS (HR=2.17 P<0.001) and PFI (HR=1.48 P<0.001) than patients with low CTSA expression. Moreover, High expressed CTSA was associated with immune cell infiltration
Conclusion: CTSA may serve as a candidate prognostic biomarker for determining prognosis associated with immune infiltration in glioma cancer.
References
2. Li D, Gao J, Yang C, Li B, Sun J, Yu M, et al. cRGDyK-modified procaine liposome inhibits the proliferation and motility of glioma cells via the ERK/p38MAPK pathway. Exp Ther Med 2021; 22(2): 859.
3. Li G, Jiang Y, Lyu X, Cai Y, Zhang M, Li G, et al. Gene signatures based on therapy responsiveness provide guidance for combined radiotherapy and chemotherapy for lower grade glioma. J Cell Mol Med 2020; 24(8): 4726-35.
4. Wang H, Xu F, Yang F, Lv L, Jiang Y. Prognostic significance and oncogene function of cathepsin A in hepatocellular carcinoma. Sci Rep 2021; 11(1): 14611.
5. Zhao YF, Han ML, Xiong YJ, Wang L, Fei Y, Shen X, et al. A miRNA-200c/cathepsin L feedback loop determines paclitaxel resistance in human lung cancer A549 cells in vitro through regulating epithelial-mesenchymal transition. Acta Pharmacol Sin 2018; 39(6): 1034-47.
6. Ruan H, Hao S, Young P, Zhang H. Targeting Cathepsin B for Cancer Therapies. Horiz Cancer Res 2015; 56: 23-40.
7. Rafn B, Nielsen CF, Andersen SH, Szyniarowski P, Corcelle-Termeau E, Valo E, et al. ErbB2-driven breast cancer cell invasion depends on a complex signaling network activating myeloid zinc finger-1-dependent cathepsin B expression. Mol Cell 2012; 45(6): 764-76.
8. Fujimoto T, Tsunedomi R, Matsukuma S, Yoshimura K, Oga A, Fujiwara N, et al. Cathepsin B is highly expressed in pancreatic cancer stem-like cells and is associated with patients' surgical outcomes. Oncol Lett 2021; 21(1): 30.
9. Ruan J, Zheng H, Rong X, Rong X, Zhang J, Fang W, et al. Over-expression of cathepsin B in hepatocellular carcinomas predicts poor prognosis of HCC patients. Mol Cancer 2016; 15: 17.
10. Kuester D, Lippert H, Roessner A, Krueger S. The cathepsin family and their role in colorectal cancer. Pathol Res Pract 2008; 204(7): 491-500.
11. Liang W, Wang F, Chen Q, Dai J, Escara-Wilke J, Keller ET, et al. Targeting cathepsin K diminishes prostate cancer establishment and growth in murine bone. J Cancer Res Clin Oncol 2019; 145(8): 1999-2012.
12. Timur ZK, Akyildiz DS, Seyrantepe V. Lysosomal Cathepsin A Plays a Significant Role in the Processing of Endogenous Bioactive Peptides. Front Mol Biosci 2016; 3: 68.
13. Hanzelmann S, Castelo R, Guinney J. GSVA: gene set variation analysis for microarray and RNA-seq data. Bmc Bioinformatics 2013; 14: 7.
14. Rotblat F, O'Brien DP, O'Brien FJ, Goodall AH, Tuddenham EG. Purification of human factor VIII:C and its characterization by Western blotting using monoclonal antibodies. Biochemistry-Us 1985; 24(16): 4294-300.
15. Li T, Yang Z, Li H, Zhu J, Wang Y, Tang Q, et al. Phospholipase Cgamma1 (PLCG1) overexpression is associated with tumor growth and poor survival in IDH wild-type lower-grade gliomas in adult patients. Lab Invest 2021:
16. Hu B, Zhu X, Lu J. Cathepsin A knockdown decreases the proliferation and invasion of A549 lung adenocarcinoma cells. Mol Med Rep 2020; 21(6): 2553-9.
17. Xiao Y, Cong M, Li J, He D, Wu Q, Tian P, et al. Cathepsin C promotes breast cancer lung metastasis by modulating neutrophil infiltration and neutrophil extracellular trap formation. Cancer Cell 2021; 39(3): 423-37.
18. Arneth B. Tumor Microenvironment. Medicina (Kaunas) 2019; 56(1): 15.
19. Yang JD, Nakamura I, Roberts LR. The tumor microenvironment in hepatocellular carcinoma: current status and therapeutic targets. Semin Cancer Biol 2011; 21(1): 35-43.
20. Hambardzumyan D, Gutmann DH, Kettenmann H. The role of microglia and macrophages in glioma maintenance and progression. Nat Neurosci 2016; 19(1): 20-7.
Copyright (c) 2022 Ming Zhang, Jun Huang, Yunfei Wang, Qingbin Nie, Xinye Zhang, Yufeng Yang, Gengsheng Mao
This work is licensed under a Creative Commons Attribution 4.0 International License.
The published articles will be distributed under the Creative Commons Attribution 4.0 International License (CC BY). It is allowed to copy and redistribute the material in any medium or format, and remix, transform, and build upon it for any purpose, even commercially, as long as appropriate credit is given to the original author(s), a link to the license is provided and it is indicated if changes were made. Users are required to provide full bibliographic description of the original publication (authors, article title, journal title, volume, issue, pages), as well as its DOI code. In electronic publishing, users are also required to link the content with both the original article published in Journal of Medical Biochemistry and the licence used.
Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.