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泛癌分析揭示了PLOD1作为人类癌症预后和免疫生物标志物的潜力。

Pan-Cancer Analysis Reveals the Potential of PLOD1 as a Prognostic and Immune Biomarker for Human Cancer.

作者信息

Zhai Zhao, Wang Shuo, Cao Yudong, Liu Jia, Zhao Qiang, Ji Yongpeng, Yang Xiao, Tang Xingxing, Ma Jinchao, Du Peng

机构信息

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Urology, Peking University Cancer Hospital & Institute, Beijing 100089, China.

出版信息

Biomedicines. 2024 Nov 21;12(12):2653. doi: 10.3390/biomedicines12122653.

Abstract

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) is known as an enhancer of collagen fiber deposition and cross-linking stability. However, there is limited information on its function in tumors. In this study, we aimed to elucidate the function and potential mechanism of action of PLOD1 across cancers. We assessed the pan-cancer expression, mutation, methylation and prognostic value of PLOD1 through multiple online databases. In addition, we performed correlation analyses of its immunological features, as well as functional assessment analyses of PLOD1. Finally, we assessed the effect of PLOD1 knockdown on bladder tumor cells using in vitro experiments. Our findings suggest that PLOD1 is aberrantly expressed in multiple cancer types, accompanied by a poor prognosis. Epigenetic alterations in PLOD1 are highly heterogeneous across a wide range of tumors, and aberrant methylation and copy number variants correlate with a poor prognosis. In the tumor microenvironment, PLOD1 expression correlated positively with the infiltration level of various immunosuppressive cells (e.g., monocytes, macrophages and tumor-associated fibroblasts) and negatively with immune-killing cells (e.g., CD8 T cells, B cells and CD4 T cells). In addition, PLOD1 expression was associated with immune checkpoints and immunomodulatory genes. Finally, in vitro experiments demonstrated that knockdown of PLOD1 reduced the proliferation, migration and antiapoptotic abilities of T24 cells. The results of this study demonstrate that PLOD1 is a potential oncogene and prognostic biomarker in pan-cancer; tumor tissues with high PLOD1 expression reveal a relatively immunosuppressive tumor microenvironment.

摘要

前胶原蛋白赖氨酸2-氧戊二酸5-双加氧酶1(PLOD1)被认为是胶原纤维沉积和交联稳定性的增强剂。然而,关于其在肿瘤中的功能信息有限。在本研究中,我们旨在阐明PLOD1在多种癌症中的功能及潜在作用机制。我们通过多个在线数据库评估了PLOD1的泛癌表达、突变、甲基化及预后价值。此外,我们对其免疫特征进行了相关性分析,并对PLOD1进行了功能评估分析。最后,我们通过体外实验评估了PLOD1基因敲低对膀胱肿瘤细胞的影响。我们的研究结果表明,PLOD1在多种癌症类型中异常表达,且预后较差。PLOD1的表观遗传改变在广泛的肿瘤中高度异质,异常甲基化和拷贝数变异与预后不良相关。在肿瘤微环境中,PLOD1表达与多种免疫抑制细胞(如单核细胞、巨噬细胞和肿瘤相关成纤维细胞)的浸润水平呈正相关,与免疫杀伤细胞(如CD8 T细胞、B细胞和CD4 T细胞)呈负相关。此外,PLOD1表达与免疫检查点和免疫调节基因相关。最后,体外实验表明,敲低PLOD1可降低T24细胞的增殖、迁移和抗凋亡能力。本研究结果表明,PLOD1是泛癌中的潜在癌基因和预后生物标志物;PLOD1高表达的肿瘤组织显示出相对免疫抑制的肿瘤微环境。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa3a/11673125/2fb81480dde8/biomedicines-12-02653-g001.jpg

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