Meng Yiming, Sun Jing, Zhang Guirong, Yu Tao, Piao Haozhe
Department of Central Laboratory, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Department of Biobank, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, China.
Front Mol Biosci. 2022 Feb 21;8:770729. doi: 10.3389/fmolb.2021.770729. eCollection 2021.
Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan-Meier method. A protein-protein interaction network was constructed using STRING software. The "ClusterProfiler" package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan-Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.
越来越多的证据表明，原胶原蛋白赖氨酸2-氧代戊二酸5-双加氧酶（PLOD）基因家族成员PLOD1、PLOD2和PLOD3与癌症进展和转移有关。然而，它们在肺腺癌（LUAD）中的表达、预后价值及其作用机制尚未见报道。我们从癌症基因组图谱（TCGA）下载了LUAD和正常组织的PLOD数据。使用临床蛋白质组肿瘤分析联盟和人类蛋白质图谱评估PLOD1-3蛋白表达。采用Kaplan-Meier方法进行生存分析。使用STRING软件构建蛋白质-蛋白质相互作用网络。使用“ClusterProfiler”软件包进行功能富集分析。使用肿瘤免疫评估资源和肿瘤免疫系统相互作用数据库分析PLOD mRNA表达与免疫浸润之间的关系。与相邻正常组织相比，LUAD组织中PLOD的表达显著上调。PLOD mRNA过表达与淋巴结转移和高TNM分期相关。受试者工作特征曲线分析表明，当截断水平为6.073时，PLOD1区分LUAD与相邻对照的准确性、敏感性和特异性分别为84.4%、79.7%和82.6%。在截断值为4.360时，PLOD2区分LUAD与相邻对照的准确性、敏感性和特异性分别为81.0%、98.3%和68.0%。在截断值为5.499时，PLOD3区分LUAD与相邻对照的准确性、敏感性和特异性分别为69.0%、86.4%和52.0%。Kaplan-Meier生存分析表明，PLOD水平高的LUAD患者预后比PLOD水平低的患者差。相关性分析表明，PLOD mRNA表达与免疫浸润和肿瘤纯度相关。PLOD表达上调与LUAD患者的不良生存和免疫细胞浸润显著相关。我们的研究表明，PLOD家族成员有潜力作为预后不良的新型生物标志物以及LUAD的潜在免疫治疗靶点。
