WANG Donglai, FENG Qi, LIU Xujian, ZHANG Xiaoyu, LIANG Zhibing, ZHANG Kaibo, DING Yan. Expression of lysine oxidase in primary lesion of esophageal cancer and its effect on prognosis of patients with bone metastases based on bioinformatics[J]. Journal of Clinical Medicine in Practice, 2024, 28(12): 12-17. DOI: 10.7619/jcmp.20241340
Citation: WANG Donglai, FENG Qi, LIU Xujian, ZHANG Xiaoyu, LIANG Zhibing, ZHANG Kaibo, DING Yan. Expression of lysine oxidase in primary lesion of esophageal cancer and its effect on prognosis of patients with bone metastases based on bioinformatics[J]. Journal of Clinical Medicine in Practice, 2024, 28(12): 12-17. DOI: 10.7619/jcmp.20241340

Expression of lysine oxidase in primary lesion of esophageal cancer and its effect on prognosis of patients with bone metastases based on bioinformatics

More Information
  • Received Date: April 01, 2024
  • Revised Date: June 06, 2024
  • Available Online: June 28, 2024
  • Objective 

    To explore the expression and clinical significance of lysine oxidase (Lox) in primary lesion of esophageal carcinoma (ESCA) and bone metastasis lesion based on bioinformatics.

    Methods 

    The Cancer Genome Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA) databases were used to screen for differentially expressed genes between ESCA and normal esophageal tissues. Follow-up information of patients with surgery for esophageal cancer in the Fourth Hospital of Hebei Medical University from January 2016 to December 2020 were screened, and the clinical materials of patients diagnosed as bone metastasis during the follow-up period were collected. Western blot was used to verify the expression of Lox in ESCA and normal esophageal tissues; immunohistochemical staining was used to detect the expression of Lox in human ESCA tissue and normal tissue; the impact of Lox expression on survival was explored by Kaplan-Meier curve and Cox regression.

    Results 

    Through the analysis of ESCA data in GEPIA and TCGA databases, it was found that the expression of Lox in ESCA lesions was significantly higher than that in normal tissues (P<0.05); the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses found that Lox may be involved in the information conduction of various signaling pathways; the Western blot result showed that the expression of Lox in cancer tissue was higher than that in adjacent normal tissue (P<0.05); the analysis of follow-up data found that patients with high expression of Lox were more likely to have multiple bone metastases; survival analysis revealed that patients with high Lox expression had significantly shorter bone metastasis free survival and overall survival compared to patients with low Lox expression (P<0.05); Cox regression found that Lox was an independent risk factor for prognosis of patients with esophageal cancer bone metastasis.

    Conclusion 

    Lox is highly expressed in ESCA and significantly related to clinical prognosis, which can be used as an effective target for the diagnosis and treatment of ESCA.

  • [1]
    YAO R, ZHANG T C, ZHANG J, et al. Effects of postoperative enteral nutrition combined with adjuvant radiotherapy on inflammatory response, nutrition, healing and prognosis in patients receiving radical surgery for esophageal carcinoma[J]. J BUON, 2019, 24(4): 1673-1678.
    [2]
    LUO H, SONG H L, MAO R H, et al. Targeting valosin-containing protein enhances the efficacy of radiation therapy in esophageal squamous cell carcinoma[J]. Cancer Sci, 2019, 110(11): 3464-3475. doi: 10.1111/cas.14184
    [3]
    MIMURA K, YAMADA L, UJⅡE D, et al. Immunotherapy for esophageal squamous cell carcinoma: a review[J]. Fukushima J Med Sci, 2018, 64(2): 46-53. doi: 10.5387/fms.2018-09
    [4]
    LAM K O, KWONG D L W. Target therapy for esophageal adenocarcinoma[J]. Methods Mol Biol, 2018, 1756: 51-65.
    [5]
    LIU K C, XIE F A, ZHAO T T, et al. Targeting SOX2 protein with peptide aptamers for therapeutic gains against esophageal squamous cell carcinoma[J]. Mol Ther, 2020, 28(3): 901-913. doi: 10.1016/j.ymthe.2020.01.012
    [6]
    GAO T T, SHAN J H, YANG Y X, et al. Comparative efficacy and safety of immunotherapy for patients with advanced or metastatic esophageal squamous cell carcinoma: a systematic review and network Meta-analysis[J]. BMC Cancer, 2022, 22(1): 992. doi: 10.1186/s12885-022-10086-5
    [7]
    HORISBERGER A, ROSA S L, ZURCHER J P, et al. A severe case of refractory esophageal stenosis induced by nivolumab and responding to tocilizumab therapy[J]. J Immunother Cancer, 2018, 6(1): 156. doi: 10.1186/s40425-018-0481-0
    [8]
    LI Y, LU Z L, CHE Y, et al. Immune signature profiling identified predictive and prognostic factors for esophageal squamous cell carcinoma[J]. Oncoimmunology, 2017, 6(11): e1356147. doi: 10.1080/2162402X.2017.1356147
    [9]
    ILSON D H, VAN HILLEGERSBERG R. Management of patients with adenocarcinoma or squamous cancer of the esophagus[J]. Gastroenterology, 2018, 154(2): 437-451. doi: 10.1053/j.gastro.2017.09.048
    [10]
    XUE M Y, TONG Y S, XIONG Y Z, et al. Role of cancer-associated fibroblasts in the progression, therapeutic resistance and targeted therapy of oesophageal squamous cell carcinoma[J]. Front Oncol, 2023, 13: 1257266. doi: 10.3389/fonc.2023.1257266
    [11]
    KALIKAWE R, BABA Y, NOMOTO D, et al. Lysyl oxidase impacts disease outcomes and correlates with global DNA hypomethylation in esophageal cancer[J]. Cancer Sci, 2019, 110(12): 3727-3737. doi: 10.1111/cas.14214
    [12]
    NAZEMI M, RAINERO E. Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer[J]. Front Oncol, 2020, 10: 239. doi: 10.3389/fonc.2020.00239
    [13]
    LI S Y, SAMPSON C, LIU C H, et al. Integrin signaling in cancer: bidirectional mechanisms and therapeutic opportunities[J]. Cell Commun Signal, 2023, 21(1): 266. doi: 10.1186/s12964-023-01264-4
    [14]
    JVNEMANN S, KLEINBÖLTING N, JAENICKE S, et al. Bioinformatics for NGS-based metagenomics and the application to biogas research[J]. J Biotechnol, 2017, 261: 10-23. doi: 10.1016/j.jbiotec.2017.08.012
    [15]
    TANG Z F, LI C W, KANG B X, et al. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses[J]. Nucleic Acids Res, 2017, 45(W1): W98-W102. doi: 10.1093/nar/gkx247
    [16]
    HENKE E, NANDIGAMA R, ERGVN S. Extracellular matrix in the tumor microenvironment and its impact on cancer therapy[J]. Front Mol Biosci, 2019, 6: 160.
    [17]
    FLIES D B, LANGERMANN S, JENSEN C, et al. Regulation of tumor immunity and immunotherapy by the tumor collagen extracellular matrix[J]. Front Immunol, 2023, 14: 1199513. doi: 10.3389/fimmu.2023.1199513
    [18]
    TENTI P, VANNUCCI L. Lysyl oxidases: linking structures and immunity in the tumor microenvironment[J]. Cancer Immunol Immunother, 2020, 69(2): 223-235. doi: 10.1007/s00262-019-02404-x
    [19]
    FEJZA A, CAROBOLANTE G, POLETTO E, et al. The entanglement of extracellular matrix molecules and immune checkpoint inhibitors in cancer: a systematic review of the literature[J]. Front Immunol, 2023, 14: 1270981. doi: 10.3389/fimmu.2023.1270981
    [20]
    MA W D, LI T, WU S, et al. Lox and ACSL5 as potential relapse markers for pancreatic cancer patients[J]. Cancer Biol Ther, 2019, 20(6): 787-798. doi: 10.1080/15384047.2018.1564565
    [21]
    ZHANG J, ZHANG L, LI C, et al. Lox-1 is a poor prognostic indicator and induces epithelial-mesenchymal transition and metastasis in pancreatic cancer patients[J]. Cell Oncol, 2018, 41(1): 73-84. doi: 10.1007/s13402-017-0360-6
    [22]
    WANG T H, HSIA S M, SHIEH T M. Lysyl oxidase and the tumor microenvironment[J]. Int J Mol Sci, 2016, 18(1): 62. doi: 10.3390/ijms18010062
    [23]
    RADICJ, KOŽIK B, NIKOLICI, et al. Multiple roles of LOXL2 in the progression of hepatocellular carcinoma and its potential for therapeutic targeting[J]. Int J Mol Sci, 2023, 24(14): 11745. doi: 10.3390/ijms241411745
    [24]
    LEO C, COTIC C, POMP V, et al. Overexpression of Lox in triple, MNBVCXZ-negative breast cancer[J]. Ann Diagn Pathol, 2018, 34: 98-102. doi: 10.1016/j.anndiagpath.2018.03.009
    [25]
    PUCCI S, POLIDORO C, GREGGI C, et al. Pro-oncogenic action of Lox-1 and its splice variant Lox-1Δ4 in breast cancer phenotypes[J]. Cell Death Dis, 2019, 10(2): 53. doi: 10.1038/s41419-018-1279-1
    [26]
    GONZÁLEZ-CHAVARRÍA I, FERNANDEZ E, GUTIERREZ N, et al. Lox-1 activation by oxLDL triggers an epithelial mesenchymal transition and promotes tumorigenic potential in prostate cancer cells[J]. Cancer Lett, 2018, 414: 34-43. doi: 10.1016/j.canlet.2017.10.035
    [27]
    NILSSON M, HÄGGLÖF C, HAMMARSTEN P, et al. H igh lysyl oxidase (Lox) in the non-malignant prostate epithelium predicts a poor outcome in prostate cancer patient managed by watchful waiting[J]. PLoS One, 2015, 10(10): e0140985. doi: 10.1371/journal.pone.0140985
    [28]
    TSUMITA T, MAISHI N, ANNAN D A M, et al. The oxidized-LDL/Lox-1 axis in tumor endothelial cells enhances metastasis by recruiting neutrophils and cancer cells[J]. Int J Cancer, 2022, 151(6): 944-956.
    [29]
    LACZKO R, CSISZAR K. Lysyl oxidase (Lox): functional contributions to signaling pathways[J]. Biomolecules, 2020, 10(8): 1093.
    [30]
    JOHNSTON K A, LOPEZ K M. Lysyl oxidase in cancer inhibition and metastasis[J]. Cancer Lett, 2018, 417: 174-181.

Catalog

    Article views (123) PDF downloads (9) Cited by()

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return