Abstract
Background
The development of human hepatocellular carcinoma (HCC) is a multistep process that
is accompanied by progressive changes in the liver microenvironment, including immune
evasion and angiogenesis. Lysyl oxidase-like 2 (LOXL2) has been suggested to contribute
to tumour progression and metastasis; however, the underlying mechanism remains unclear.
The purpose of the present study was to explore the relationship between LOXL2 and
immune infiltration and vasculogenic mimicry (VM) and to identify the role of LOXL2
in HCC diagnosis prognosis evaluation.
Methods
The Cancer Genome Atlas (TCGA), UALCAN, GEPIA and Kaplan–Meier plotter databases were
used to analyse LOXL2 expression and perform survival analysis. The Tumour Immune
Estimation Resource (TIMER) was used to analyse immune cell infiltration, immune cell
biomarkers and immune checkpoints. Immunohistochemistry (IHC) of 201 HCC samples was
used to confirm the expression of LOXL2 and its relationship with VM. Coimmunoprecipitation
(co-IP) and gain- and loss-of-function studies were performed to confirm the molecular
mechanism of LOXL2 in VM.
Results
The expression of LOXL2 in HCC was higher than that in normal tissues at both the
mRNA and protein levels. High expression of LOXL2 was associated with a poorer prognosis
of HCC. The genetic alteration rate of LOXL2 was 5%. LOXL2 was positively related
to immune cell infiltration and immune checkpoints (PD-1 and CTLA-4) in HCC. Co-IP
showed that LOXL2 can interact directly with IQGAP1. Both gain- and loss-of-function
studies showed that LOXL2 significantly induced cell migration, invasion and VM formation
when IQGAP1 was upregulated.
Conclusions
LOXL2 is involved in immune cell infiltration and promotes VM by upregulating IQGAP1.
LOXL2 can be used as a novel biomarker for HCC diagnosis and prognosis prediction.
Keywords
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Article Info
Publication History
Published online: October 01, 2022
Accepted:
September 7,
2022
Received:
July 1,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2022 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
