Identification of LOXL3-associating immune infiltration landscape and prognostic value in hepatocellular carcinoma

In recent years, breakthroughs in the field of tumor immunotherapy with immune checkpoint inhibitors (ICIs) have made a therapeutic revolution, which has been shown to improve the prognosis of patients with hepatocellular carcinoma (HCC). Immune infiltrates represent a major component of tumor microenvironment (TME), and play an essential role in both tumor progression and therapeutic response. The major unmet challenge in tumor immunotherapy is exploring the intrinsic and extrinsic mechanisms of TME promoting the management of HCC. Lysyl oxidase like 3 (LOXL3) participates in the remodeling of extracellular matrix (ECM) and the cross-linking of collagen and elastic fibers. It has been reported that LOXL3 is associated with the development and tumorigenesis of multiple types of cancer. RNA sequencing data and corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) databases, then subjected to gene expression, tumor microenvironment, survival, enrichment analyses utilizing R packages. In this study, we first found that LOXL3 gene was upregulated in tumor tissues compared with the normal tissues. Furthermore, LOXL3 expression is positively correlated with the infiltration of multiple immune cells and the expression of immune checkpoint genes in HCC. Meanwhile, high LOXL3 expression predicted poor outcomes of the patients with HCC. Functional enrichment analysis suggested that LOXL3 was mainly linked to extracellular structure and matrix organization, cell-cell adhesion, and T cell activation. This is the first comprehensive study to indicate that LOXL3 is correlated with immune infiltrates and may serve as a novel biomarker predicting prognosis and immunotherapy in HCC.

Automated summary

This study identified that LOXL3 gene expression is upregulated in tumor tissues, positively correlated with multiple immune cell infiltrates and immune checkpoint gene expression in HCC, and associated with poor outcomes of HCC patients. Functional enrichment analysis revealed that LOXL3 is mainly involved in extracellular structure and matrix organization, cell-cell adhesion, and T cell activation, suggesting its potential as a novel biomarker for predicting prognosis and guiding immunotherapy in HCC.