Department of Orthopaedics, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Clinical Research Center, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
Front Immunol. 2021 Oct 6;12:758845. doi: 10.3389/fimmu.2021.758845. eCollection 2021.
G protein subunit gamma 12 (GNG12) is observed in some types of cancer, but its role in osteosarcoma is unknown. This study hypothesized that GNG12 may be a potential biomarker and therapeutic target. We aimed to identify an association between GNG12 and osteosarcoma based on the Gene Expression Omnibus and the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) databases.
Osteosarcoma samples in GSE42352 and TARGET database were selected as the test cohorts. As the external validation cohort, 78 osteosarcoma specimens from The Second Affiliated Hospital of Nanchang University were collected. Patients with osteosarcoma were divided into high and low GNG12 mRNA-expression groups; differentially expressed genes were identified as GNG12-related genes. The biological function of GNG12 was annotated using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set enrichment analysis, and immune infiltration analysis. Gene expression correlation analysis and competing endogenous RNA regulatory network construction were used to determine potential biological regulatory relationships of GNG12. Overall survival, Kaplan-Meier analysis, and log-rank tests were calculated to determine GNG12 reliability in predicting survival prognosis.
GNG12 expression decreased in osteosarcoma samples. GNG12 was a highly effective biomarker for osteosarcoma [area under the receiver operating characteristic (ROC) curve (AUC) = 0.920], and the results of our Kaplan-Meier analysis indicated that overall survival and progression-free survival differed significantly between low and high GNG-expression group (p < 0.05). Functional analyses indicated that GNG12 may promote osteosarcoma through regulating the endoplasmic reticulum. Expression correlation analysis and competing endogenous RNA network construction showed that HOTTIP/miR-27a-3p may regulate GNG12 expression. Furthermore, the subunit suppresses adaptive immunity inhibiting M1 and M2 macrophage infiltration. GNG12 was inhibited in metastatic osteosarcoma compared with non-metastatic osteosarcoma, and its expression predicted survival of patients (1, 3, and 5-year AUCs were 0.961, 0.826, and 0.808, respectively).
This study identified GNG12 as a potential biomarker for osteosarcoma prognosis, highlighting its potential as an immunotherapy target.
G 蛋白亚单位 γ12（GNG12）存在于某些类型的癌症中，但它在骨肉瘤中的作用尚不清楚。本研究假设 GNG12 可能是一种潜在的生物标志物和治疗靶点。我们旨在基于基因表达综合数据库和治疗性应用研究以产生有效的治疗方法（TARGET）数据库来鉴定 GNG12 与骨肉瘤之间的关联。
选择 GSE42352 和 TARGET 数据库中的骨肉瘤样本作为测试队列。南昌大学第二附属医院的 78 例骨肉瘤标本作为外部验证队列。将骨肉瘤患者分为高和低 GNG12mRNA 表达组；鉴定差异表达的基因作为与 GNG12 相关的基因。使用基因本体论、京都基因与基因组百科全书、基因集富集分析和免疫浸润分析对 GNG12 的生物学功能进行注释。进行基因表达相关性分析和竞争性内源 RNA 调控网络构建，以确定 GNG12 潜在的生物学调控关系。进行总体生存、Kaplan-Meier 分析和对数秩检验，以确定 GNG12 在预测生存预后方面的可靠性。
GNG12 在骨肉瘤样本中的表达降低。GNG12 是骨肉瘤的一种非常有效的生物标志物[受试者工作特征曲线（ROC）下面积（AUC）=0.920]，我们的 Kaplan-Meier 分析结果表明，低和高 GNG 表达组之间的总生存率和无进展生存率差异有统计学意义（p<0.05）。功能分析表明，GNG12 可能通过调节内质网促进骨肉瘤的发生。表达相关性分析和竞争性内源 RNA 网络构建表明，HOTTIP/miR-27a-3p 可能调节 GNG12 的表达。此外，该亚基通过抑制 M1 和 M2 巨噬细胞浸润来抑制适应性免疫。与非转移性骨肉瘤相比，转移性骨肉瘤中 GNG12 受到抑制，其表达可预测患者的生存（1、3 和 5 年 AUC 分别为 0.961、0.826 和 0.808）。
本研究将 GNG12 确定为骨肉瘤预后的潜在生物标志物，突出了其作为免疫治疗靶点的潜力。
