Abstract
BackgroundG 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.MethodsOsteosarcoma 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.ResultsGNG12 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 via 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).ConclusionThis study identified GNG12 as a potential biomarker for osteosarcoma prognosis, highlighting its potential as an immunotherapy target.
Highlights
Osteosarcoma is among the most common primary solid malignant bone tumors in adolescents and young adults
Our results demonstrated that low G protein subunit gamma 12 (GNG12) expression is a potential biomarker of osteosarcoma, linked to poor prognosis
After screening for DEGs between high and low GNG12-expression groups (Figure 1B), we found 210 coexpressed genes (165 upregulated and 45 downregulated, Supplementary Table 1) that we have visualized in a volcano plot (Figure 1D) and a heat map (Figure 1E)
Summary
Osteosarcoma is among the most common primary solid malignant bone tumors in adolescents and young adults. The progress of research aiming to raise osteosarcoma survival has stalled over the past 30 years [4]. It is critical to determine reliable predictors related to osteosarcoma metastasis and prognosis and to make available novel targets for therapy and prognosis prediction. It is crucial to find novel prognostic biomarkers to predict survival and metastases more accurately in osteosarcoma. Biomarkers such as FAT10 and MYC have been associated with osteosarcoma in recent studies, their reliability requires further investigation [5, 6]. 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
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