The collagen-modifying enzyme GLT25D1 is a prognostic indicator related to immunosuppression and malignant phenotypes in hepatocellular carcinoma.

IF 5.3 2区 医学 Q1 ONCOLOGY
Sheng Qiu, Hongdong Han, Hongmin Zhang, Mengliu Yang, Hao Wang, Ke Li, Ling Li, Gangyi Yang
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引用次数: 0

Abstract

Background: The collagen β (1-O) glycosyltransferase 25 domain 1 (GLT25D1), a crucial collagen-modifying enzyme (CME), plays a pivotal role in multiple pathophysiological processes. However, its prognostic and biological roles in hepatocellular carcinoma (HCC) have not been reported.

Methods: CME-related genes (CMEGs) were obtained from the Molecular Signatures Database (MSigDB), differentially expressed CMEGs (DECMEGs) and prognostic ones were identified. GLT25D1 expression was determined at the mRNA and protein levels in multiple datasets and in our HCC cohort. Its prognostic performance was evaluated and the immune microenvironment was investigated. The effects of GLT25D1 on tumorigenesis were further explored via in vitro and in vivo experiments.

Results: Four potential prognosis-associated DECMEGs, including GLT25D1, were identified. GLT25D1 was noticeably up-regulated in HCC tissues and significantly associated with advanced tumor grade and stage. Enrichment analysis revealed that GLT25D1 could participate in regulating immune responses and various carcinogenic processes. HCC patients with high GLT25D1 expression had decreased CD8+ T cells and increased M0 macrophages, leading to an immunosuppressive microenvironment. Our in vivo and in vitro experiments confirmed the increased GLT25D1 expression, and GLT25D1 knockdown impaired the HCC malignant phenotypes.

Conclusions: Our results showed that GLT25D1 could be a carcinogenic indicator reflecting poor prognosis and might serve as a potential risk biomarker for HCC patients.

胶原修饰酶GLT25D1是肝细胞癌中与免疫抑制和恶性表型相关的预后指标。
背景:胶原β (1- o)糖基转移酶25结构域1 (GLT25D1)是一种重要的胶原修饰酶(CME),在多种病理生理过程中起关键作用。然而,其在肝细胞癌(HCC)中的预后和生物学作用尚未报道。方法:从分子特征数据库(MSigDB)中获取cme相关基因(CMEGs),鉴定差异表达CMEGs (DECMEGs)和预后基因。在多个数据集和我们的HCC队列中,GLT25D1在mRNA和蛋白水平上的表达被确定。评估其预后性能并研究免疫微环境。通过体外和体内实验进一步探讨GLT25D1对肿瘤发生的影响。结果:确定了四种可能与预后相关的decmeg,包括GLT25D1。GLT25D1在HCC组织中表达明显上调,且与肿瘤分级和分期显著相关。富集分析显示,GLT25D1参与调节免疫应答和多种致癌过程。GLT25D1高表达的HCC患者CD8+ T细胞减少,M0巨噬细胞增加,导致免疫抑制微环境。我们的体内和体外实验证实GLT25D1表达增加,GLT25D1敲低可损害HCC的恶性表型。结论:我们的研究结果表明GLT25D1可能是反映预后不良的致癌指标,可能是HCC患者潜在的风险生物标志物。
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来源期刊
CiteScore
10.90
自引率
1.70%
发文量
360
审稿时长
1 months
期刊介绍: Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.
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