Tianjin Third Central Hospital, 83 Jintang Road, Hedong District, Tianjin, 300170, China.
Department of Nephrology, Tianjin Haihe Hospital, Haihe Clinical College of Tianjin Medical University, Tianjin, 300350, China.
Virchows Arch. 2021 Dec;479(6):1153-1165. doi: 10.1007/s00428-021-03193-4. Epub 2021 Aug 27.
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治疗革命，已证明其可改善肝细胞癌（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起着至关重要的作用。肿瘤免疫治疗的主要未满足的挑战是探索 TME 的内在和外在机制，以促进 HCC 的管理。赖氨酰氧化酶样 3（LOXL3）参与细胞外基质（ECM）的重塑和胶原及弹性纤维的交联。已有报道称，LOXL3 与多种类型癌症的发生和肿瘤发生有关。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，然后利用 R 包进行基因表达、肿瘤微环境、生存和富集分析。在这项研究中，我们首先发现 LOXL3 基因在肿瘤组织中的表达高于正常组织。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 患者的预后不良。功能富集分析表明，LOXL3 主要与细胞外结构和基质组织、细胞间黏附以及 T 细胞激活有关。这是第一项全面研究表明 LOXL3 与免疫浸润相关，并可能作为预测 HCC 预后和免疫治疗的新型生物标志物。
