Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 26;15(1):245.
doi: 10.1007/s12672-024-01107-9.

The role of LOXL2 in tumor progression, immune response and cellular senescence: a comprehensive analysis

Chen Ye #  1   2 , Sihan Jiang #  3 , Tanlun Zeng  3   4 , Shaohui He  2 , Jinjin Cao  5   6 , Jianru Xiao  7   8
Affiliations

The role of LOXL2 in tumor progression, immune response and cellular senescence: a comprehensive analysis

Chen Ye et al. Discov Oncol. .

Abstract

LOXL2, an enzyme belonging to the LOX family, facilitates the cross-linking of extracellular matrix (ECM) elements. However, the roles of the LOXL2 gene in mechanisms of oncogenesis and tumor development have not been clearly defined. In this pan-cancer study, we examined the notable disparity in LOXL2 expression at the mRNA and protein levels among various cancer types and elucidated its interconnected roles in tumor progression, mutational profile, immune response, and cellular senescence. Apart from investigating the hyperexpression of LOXL2 being related to poorer prognosis in different types of tumors, this study also unveiled noteworthy connections between LOXL2 and genetic mutations, infiltration of tumor immune cells, and genes in immune checkpoint pathways. Further analysis revealed the participation of LOXL2 in multiple pathways related to cancer extracellular matrix remodeling and cellular senescence. Moreover, our investigation uncovered that the knockdown and inhibition of LOXL2 significantly attenuated the proliferation and migration of PC-9 and HCC-LM3 cells. The knock-down and inhibition of LOXL2 enhanced cellular senescence in lung and liver cancer cells, as confirmed by SA-β-Gal staining and quantitative RT-PCR analyses. This comprehensive analysis offers valuable insights on the functions of LOXL2 in different types of cancer and its role in regulating the senescence of cancer cells.

Keywords: Cellular senescence; Immunity; LOXL2; Pan-cancer analysis; Prognosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
A For unpaired normal and tumor samples, mRNA expression levels of LOXL2 in different cancers were analyzed via the TCGA database, MESO and UVM lack normal tissue data; B Protein expression of LOXL2 in different normal and tumor tissues was analyzed via the CPTAC database; C The IHC staining results of LOXL2 expression in lung, breast, and liver cancers were obtained via the HPA database. * p < 0.05, **p < 0.01, and ***p < 0.001
Fig. 2
Fig. 2
A The relationship between LOXL2 expression and OS was analyzed using the univariate Cox regression method in pan-cancer. In the TCGA database, Kaplan–Meier methodology was used to compare the expression of LOXL2 in different cancer types, showing OS curves for high and low expression; B–D The association between LOXL2 expression and DSS, DFI, and PFI was analyzed using univariate Cox regression analysis
Fig. 3
Fig. 3
A The mutation profile of LOXL2 revealed “Deep Deletion” was the major type of mutation by TCGA; B The mutational landscape of LOXL2 across various cancers was examined by TCGA; C Genetic alteration disparities in UCEC, SKCM, COAD, and ESCA with varying expression levels of LOXL2 by TCGA; D, E The correlation of survival with LOXL2 SNV and CNV in pan-cancer via GSCA.
Fig. 4
Fig. 4
A Heatmap showing correlations of LOXL2 expression with immune infiltration level in various TCGA cancer types using TIMER; B Heatmap of relationships of LOXL2 expression with infiltrated cells in various TCGA cancer types using xCell; C The connection between LOXL2 expression and genes in immune checkpoint pathways; D The correlation of LOXL2 expression and stromal scores, immune scores in pan-cancer via ESTIMATE and TCGA databases
Fig. 5
Fig. 5
A Through GeneMANIA, LOXL2 and its molecular partners form a PPI network; B KEGG enrichment analysis of the gene set from GEPIA2; C GSEA analysis of LOXL2 in different cancers. Various colored curves represent distinct functions or pathways controlled by various types of cancer. Positive regulation is indicated by peaks on the ascending curve, while negative regulation is indicated by peaks on the descending curve.
Fig. 6
Fig. 6
A The impact of LOXL2 on cell proliferation in PC-9 and HCC-LM3 cells was assessed using the CCK8 assay at 24, 48, 72, and 96 h; B The migration ability of PC-9 and HCC-LM3 cells was compromised by both LOXL2 knockdown and the LOXL2 inhibitor. Scale bar = 500 µm. The statistical findings from the scratch wound-healing assays at 24 h are displayed as the average plus standard deviation (three replicates). * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001
Fig. 7
Fig. 7
A Cellular senescence was detected by SA-β-gal staining. Scale bar = 200 µm; B Cellular senescence-related gene expression in PC-9 and HCC-LM3 cells transfected with siRNA-LOXL2 and inhibitor, and control siRNA. * P < 0.05
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Soerjomataram I, Bray F. Planning for tomorrow: global cancer incidence and the role of prevention 2020–2070. Nat Rev Clin Oncol. 2021;18:663–672. doi: 10.1038/s41571-021-00514-z. - DOI - PubMed
    1. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin. 2021;71:7–33. doi: 10.3322/caac.21654. - DOI - PubMed
    1. Robert L, Ribas A, Hu-Lieskovan S. Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2? Semin Immunol. 2016;28:73–80. doi: 10.1016/j.smim.2016.01.001. - DOI - PMC - PubMed
    1. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–354. doi: 10.1038/nature12626. - DOI - PubMed
    1. Fane M, Harris L, Smith AG, Piper M. Nuclear factor one transcription factors as epigenetic regulators in cancer. Int J Cancer. 2017;140:2634–2641. doi: 10.1002/ijc.30603. - DOI - PubMed

LinkOut - more resources