WANG Qiqi, YE Bicheng, WANG Changcheng. Correlation between AHSA1 expression and prognosis of hepatocellular carcinoma based on TCGA database analysis[J]. Journal of Clinical Medicine in Practice, 2022, 26(1): 8-17. DOI: 10.7619/jcmp.20213231
Citation: WANG Qiqi, YE Bicheng, WANG Changcheng. Correlation between AHSA1 expression and prognosis of hepatocellular carcinoma based on TCGA database analysis[J]. Journal of Clinical Medicine in Practice, 2022, 26(1): 8-17. DOI: 10.7619/jcmp.20213231

Correlation between AHSA1 expression and prognosis of hepatocellular carcinoma based on TCGA database analysis

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  • Received Date: August 09, 2021
  • Available Online: January 03, 2022
  • Published Date: January 14, 2022
  •   Objective  To investigate the expression of activator of heat shock 90 kDa protein ATPase homolog 1 (AHSA1) in hepatocellular carcinoma (HCC) and analyze the relationship between AHSA1 expression level and prognosis.
      Methods  HCCDB, GEPIA and Oncomine databases were used to analyze the expression of AHSA1 mRNA in HCC and normal liver tissues. HCC RNA-seq expression and clinical information were downloaded from the Cancer Genome Atlas (TCGA), and univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the value of AHSA1 in predicting the prognosis of liver cancer. R software was used to construct the nomogram based on the expression level of AHSA1, and the calibration curve was plotted to evaluate the consistency between the actual survival and the predicted survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set enrichment analyses were perform to reveal tumor-associated biological processes related to AHSA1. The TIMER2.0 and GFPIA database were used to evaluate the correlation between AHSAl and tumor immune infiltration in HCC. Small molecule targeted drugs acting on AHSA1 were screened by CMAP.
      Results  The expression level of AHSA1 in HCC tissues was significantly higher than that in normal tissues (P < 0.01). High expression of AHSA1 was associated with the poor prognosis of HCC (P < 0.05), and was an independent factor affecting overall survival (OS) (HR=1.970, P < 0.001). The nomogram showed that AHSA1 gene expression was correlated with the risk of HCC, and the area under the curve (AUC) of predicting OS at 1 year, 3 and 5 years were 0.721, 0.711 and 0.725, respectively. The calibration chart showed that the predicted survival rate curve was in good agreement with the actual survival rate curve. GO and KEGG enrichment analysis showed that AHSAl was able to promote tumor progression by mediating neutrophil activation and participating in biological processes such as glycolysis and gluconeogenesis. The expression level of AHSA1 mRNA was associated with the degrees of immune infiltration by B cells, CD4+ T cells, regulatory T cells, macrophages, neutrophils and dendritic cells (P < 0.05). Etacrynic acid and blebbistatin might be the small molecule targeted drugs that can reverse the expression of AHSA1.
      Conclusion  AHSA1 mRNA may be a potential oncogene in HCC, the high expression of AHSA1 mRNA may promote the immune infiltration of HCC tissues, and is associated with poor prognosis of HCC patients.
  • [1]
    JEMAL A, WARD E M, JOHNSON C J, et al. Annual Report to the Nation on the Status of Cancer, 1975-2014, Featuring Survival[J]. J Natl Cancer Inst, 2017, 109(9): djx030. http://chdi.wiscweb.wisc.edu/wp-content/uploads/sites/620/2018/06/djx030.pdf
    [2]
    OROZ J, BLAIR L J, ZWECKSTETTER M. Dynamic Aha1 co-chaperone binding to human Hsp90[J]. Protein Sci, 2019, 28(9): 1545-1551. doi: 10.1002/pro.3678
    [3]
    WORTMANN P, GÖTZ M, HUGEL T. Cooperative Nucleotide Binding in Hsp90 and Its Regulation by Aha1[J]. Biophys J, 2017, 113(8): 1711-1718. doi: 10.1016/j.bpj.2017.08.032
    [4]
    HOLMES J L, SHARP S Y, HOBBS S, et al. Silencing of HSP90 cochaperone AHA1 expression decreases client protein activation and increases cellular sensitivity to the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin[J]. Cancer Res, 2008, 68(4): 1188-1197. doi: 10.1158/0008-5472.CAN-07-3268
    [5]
    WOLMARANS A, LEE B, SPYRACOPOULOS L, et al. The Mechanism of Hsp90 ATPase Stimulation by Aha1[J]. Sci Rep, 2016, 6: 33179. doi: 10.1038/srep33179
    [6]
    WANDINGER S K, RICHTER K, BUCHNER J. The Hsp90 chaperone machinery[J]. J Biol Chem, 2008, 283(27): 18473-18477. doi: 10.1074/jbc.R800007200
    [7]
    LIU H J, JIANG X X, GUO Y Z, et al. The flavonoid TL-2-8 induces cell death and immature mitophagy in breast cancer cells via abrogating the function of the AHA1/Hsp90 complex[J]. Acta Pharmacol Sin, 2017, 38(10): 1381-1393. doi: 10.1038/aps.2017.9
    [8]
    ZHENG D, LIU W, XIE W, et al. AHA1 upregulates IDH1 and metabolic activity to promote growth and metastasis and predicts prognosis in osteosarcoma[J]. Signal Transduct Target Ther, 2021, 6(1): 25. doi: 10.1038/s41392-020-00387-1
    [9]
    ZHANG Y, ZHANG Y, LIN Q H. Progesterone-modulated proteins in human endometrial cancer cell line Ishikawa[J]. Nan Fang Yi Ke Da Xue Xue Bao, 2006, 26(8): 1110-1113. http://www.ncbi.nlm.nih.gov/pubmed/16939895
    [10]
    HEIDER M, EICHNER R, STROH J, et al. The IMiD target CRBN determines HSP90 activity toward transmembrane proteins essential in multiple myeloma[J]. Mol Cell, 2021, 81(6): 1170-1186, e10. doi: 10.1016/j.molcel.2020.12.046
    [11]
    KOCHHAR A, KOPELOVICH L, SUE E, et al. p53 modulates Hsp90 ATPase activity and regulates aryl hydrocarbon receptor signaling[J]. Cancer Prev Res (Phila), 2014, 7(6): 596-606. doi: 10.1158/1940-6207.CAPR-14-0051
    [12]
    BAKER-WILLIAMS A J, HASHMI F, BUDZYNSKI M A, et al. Co-chaperones TIMP2 and AHA1 Competitively Regulate Extracellular HSP90: Client MMP2 Activity and Matrix Proteolysis[J]. Cell Rep, 2019, 28(7): 1894-1906, e6. doi: 10.1016/j.celrep.2019.07.045
    [13]
    CAO R, SHAO J, HU Y, et al. microRNA-338-3p inhibits proliferation, migration, invasion, and EMT in osteosarcoma cells by targeting activator of 90 kDa heat shock protein ATPase homolog 1[J]. Cancer Cell Int, 2018, 18: 49. doi: 10.1186/s12935-018-0551-x
    [14]
    KLAUSCHEN F, MVLLER K R, BINDER A, et al. Scoring of tumor-infiltrating lymphocytes: From visual estimation to machine learning[J]. Semin Cancer Biol, 2018, 52(Pt 2): 151-157. http://www.onacademic.com/detail/journal_1000040435720910_e056.html
    [15]
    LIPSON E J, DRAKE C G. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma[J]. Clin Cancer Res, 2011, 17(22): 6958-6962. doi: 10.1158/1078-0432.CCR-11-1595
    [16]
    HELLMANN M D, NATHANSON T, RIZVI H, et al. Genomic Features of Response to Combination Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer[J]. Cancer Cell, 2018, 33(5): 843-852, e4. doi: 10.1016/j.ccell.2018.03.018
    [17]
    ZHANG H H, MEI M H, FEI R, et al. Regulatory T cells in chronic hepatitis B patients affect the immunopathogenesis of hepatocellular carcinoma by suppressing the anti-tumour immune responses[J]. J Viral Hepat, 2010, 17(Suppl 1): 34-43. http://labs.europepmc.org/abstract/MED/20586932
    [18]
    HONG G Q, CAI D, GONG J P, et al. Innate immune cells and their interaction with T cells in hepatocellular carcinoma[J]. Oncol Lett, 2021, 21(1): 57. http://www.researchgate.net/publication/347062334_Innate_immune_cells_and_their_interaction_with_T_cells_in_hepatocellular_carcinoma_Review
    [19]
    LIU J, FAN L, YU H, et al. Endoplasmic Reticulum Stress Causes Liver Cancer Cells to Release Exosomal miR-23a-3p and Up-regulate Programmed Death Ligand 1 Expression in Macrophages[J]. Hepatology, 2019, 70(1): 241-258.
    [20]
    FU J, XU D, LIU Z, et al. Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients[J]. Gastroenterology, 2007, 132(7): 2328-2339. doi: 10.1053/j.gastro.2007.03.102
    [21]
    ARIHARA F, MIZUKOSHI E, KITAHARA M, et al. Increase in CD14+ HLA-DR-/low myeloid-derived suppressor cells in hepatocellular carcinoma patients and its impact on prognosis[J]. Cancer Immunol Immunother, 2013, 62(8): 1421-1430. doi: 10.1007/s00262-013-1447-1
    [22]
    LANGHANS B, NISCHALKE H D, KRÄMER B, et al. Role of regulatory T cells and checkpoint inhibition in hepatocellular carcinoma[J]. Cancer Immunol Immunother, 2019, 68(12): 2055-2066. doi: 10.1007/s00262-019-02427-4
    [23]
    HINDLEY J P, FERREIRA C, JONES E, et al. Analysis of the T-cell receptor repertoires of tumor-infiltrating conventional and regulatory T cells reveals no evidence for conversion in carcinogen-induced tumors[J]. Cancer Res, 2011, 71(3): 736-746. doi: 10.1158/0008-5472.CAN-10-1797
    [24]
    LU C, RONG D, ZHANG B, et al. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities[J]. Mol Cancer, 2019, 18(1): 130. doi: 10.1186/s12943-019-1047-6
    [25]
    KITAMURA T, QIAN B Z, POLLARD J W. Immune cell promotion of metastasis[J]. Nat Rev Immunol, 2015, 15(2): 73-86. doi: 10.1038/nri3789
    [26]
    BORST J, AHRENDS T, BABAŁA N, et al. CD4(+) T cell help in cancer immunology and immunotherapy[J]. Nat Rev Immunol, 2018, 18(10): 635-647. doi: 10.1038/s41577-018-0044-0
    [27]
    FARHOOD B, NAJAFI M, MORTEZAEE K. CD8(+) cytotoxic T lymphocytes in cancer immunotherapy: A review[J]. J Cell Physiol, 2019, 234(6): 8509-8521. doi: 10.1002/jcp.27782
    [28]
    GHOSH S, SHINOGLE H E, GARG G, et al. Hsp90 C-terminal inhibitors exhibit antimigratory activity by disrupting the Hsp90α/Aha1 complex in PC3-MM2 cells[J]. ACS Chem Biol, 2015, 10(2): 577-590. doi: 10.1021/cb5008713
    [29]
    STIEGLER S C, RVBBELKE M, KOROTKOV V S, et al. A chemical compound inhibiting the Aha1-Hsp90 chaperone complex[J]. J Biol Chem, 2017, 292(41): 17073-17083. doi: 10.1074/jbc.M117.797829
    [30]
    PARODY J P, ALVAREZ MDE L, QUIROGA A, et al. Hepatocytes isolated from preneoplastic rat livers are resistant to ethacrynic acid cytotoxicity[J]. Arch Toxicol, 2007, 81(8): 565-573. doi: 10.1007/s00204-007-0183-8
    [31]
    MISHRA M, JAYAL P, KARANDE A A, et al. Identification of a co-target for enhancing efficacy of sorafenib in HCC through a quantitative modeling approach[J]. Febs j, 2018, 285(21): 3977-3992. doi: 10.1111/febs.14641
    [32]
    AL-DALI A M, WEIHER H, SCHMIDT-WOLF I G H. Utilizing ethacrynic acid and ciclopirox olamine in liver cancer[J]. Oncol Lett, 2018, 16(5): 6854-6860. doi: 10.3892/ol.2018.9472/download
    [33]
    ROMAN B I, VERHASSELT S, STEVENS C V. Medicinal Chemistry and Use of Myosin Ⅱ Inhibitor (S)-Blebbistatin and Its Derivatives[J]. J Med Chem, 2018, 61(21): 9410-9428. doi: 10.1021/acs.jmedchem.8b00503
    [34]
    DUXBURY M S, ASHLEY S W, WHANG E E. Inhibition of pancreatic adenocarcinoma cellular invasiveness by blebbistatin: a novel myosin Ⅱ inhibitor[J]. Biochem Biophys Res Commun, 2004, 313(4): 992-997. doi: 10.1016/j.bbrc.2003.12.031
    [35]
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