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.

近年来，免疫检查点抑制剂（ICIs）在肿瘤免疫治疗领域的突破带来了一场治疗革命，已被证明可以改善肝细胞癌（HCC）患者的预后。免疫浸润是肿瘤微环境 (TME) 的主要组成部分，在肿瘤进展和治疗反应中都发挥着重要作用。肿瘤免疫治疗中尚未解决的主要挑战是探索 TME 促进 HCC 管理的内在和外在机制。赖氨酰氧化酶样 3 (LOXL3) 参与细胞外基质 (ECM) 的重塑以及胶原蛋白和弹性纤维的交联。据报道，LOXL3与多种癌症的发展和肿瘤发生有关。从癌症基因组图谱 (TCGA) 数据库中提取 RNA 测序数据和相应的临床信息，然后使用 R 包进行基因表达、肿瘤微环境、生存、富集分析。在这项研究中，我们首先发现与正常组织相比，肿瘤组织中的 LOXL3 基因上调。此外，LOXL3的表达与HCC中多种免疫细胞的浸润和免疫检查点基因的表达呈正相关。同时，高 LOXL3 表达预示着 HCC 患者的不良预后。功能富集分析表明，LOXL3 主要与细胞外结构和基质组织、细胞-细胞粘附和 T 细胞活化有关。