Abstract
BackgroundLiver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis.ResultsThe expression levels of all LOX family members were significantly increased in LC. Area under the receiver operating characteristic curve (AUC) of LOXL2 was 0.946 with positive predictive value (PPV) of 0.994. LOX and LOXL3 were correlated with worse prognosis. Meta-analysis also validated effect of LOX on prognosis. Nomogram of these two genes and other predictors was also plotted. There was insufficient data from original studies to conduct meta-analysis on LOXL3. The functions of LOX family members in LC were mostly involved in extracellular and functions and structures. The expressions of LOX family members strongly correlated with various immune infiltrating cells and immunomodulators in LC.ConclusionsFor LC patients, LOXL2 may be a potential diagnostic biomarker, while LOX and LOXL3 have potential prognostic and therapeutic values. Positive correlation between LOX family and infiltration of various immune cells and immunomodulators suggests the need for exploration of their roles in the tumor microenvironment and for potential immunotherapeutic to target LOX family proteins.
Highlights
Liver cancer (LC) is well known for its prevalence as well as its poor prognosis
All five members of lysyl oxidase (LOX) family demonstrated higher expression in liver cancer tumor tissues than normal tissues (Figure 1A and Table 1). These findings were consistent with results from UALCAN, which confirmed that the expression of all LOX family members was statistically significantly higher in tumor tissue (Figure 1B), and from Tumor Immune Estimation Resource (TIMER), which showed higher expression of LOX (P=1.5E-11), LOXL1 (P=2.39E-04), LOXL2 (P=4.02E-25), LOXL3 (P=1.53E-04), and LOXL4 (P=7.15-05)
Further analysis of receiver operating characteristic (ROC) curve showed that area under the curve (AUC) of LOXL2 was 0.946 (95%confidence interval (CI):0.915-0.978, with positive predictive value (PPV) of 0.994 and a cutoff value of 1.050 (Figure 2)
Summary
Liver cancer (LC) is well known for its prevalence as well as its poor prognosis. The aberrant expression of lysyl oxidase (LOX) family is associated with liver cancer, but their function and prognostic value in LC remain largely unclear. This study aimed to explore the function and prognostic value of LOX family in LC through bioinformatics analysis and meta-analysis. Hepatocellular carcinoma (HCC) accounts for 75%-85% of all LC, according to the GLOBOCAN 2020 estimation [1]. In east Asia, especially China, a high incidence of HCC was noted, and the incidence and mortality of LC in developing countries are significantly higher than those in developed countries [2, 3]. Despite significant advances in diagnosis and treatment of LC, including surgical resection, local ablation, liver transplantation, and sorafenib–regorafenib sequential therapy, the prognosis of LC remains poor [6]. It is of great value to explore novel diagnostic and prognostic biomarkers that are sensitive and specific, and to identify potential targets for medications [7]
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