High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification

Jiang，Xiaohong1,2; Tang，Fuxing3,4; Zhang，Junlei5; He，Mingwei1; Xie，Tianyu1; Tang，Haijun3; Liu，Jianhong1; Luo，Kai3; Lu，Shenglin2; Liu，Yun2; Lu，Jili6; He，Maolin3; Wei，Qingjun1

2023-02-10

10.3389/fonc.2023.991483

Frontiers in Oncology   影响因子和分区

2234-943X

Background: Guanine nucleotide binding (G) protein subunit γ 4 (GNG4) is closely related to the malignant progression and poor prognosis of various tumours. However, its role and mechanism in osteosarcoma remain unclear. This study aimed to elucidate the biological role and prognostic value of GNG4 in osteosarcoma. Methods: Osteosarcoma samples in the GSE12865, GSE14359, GSE162454 and TARGET datasets were selected as the test cohorts. The expression level of GNG4 between normal and osteosarcoma was identified in GSE12865 and GSE14359. Based on the osteosarcoma single-cell RNA sequencing (scRNA-seq) dataset GSE162454, differential expression of GNG4 among cell subsets was identified at the single-cell level. As the external validation cohort, 58 osteosarcoma specimens from the First Affiliated Hospital of Guangxi Medical University were collected. Patients with osteosarcoma were divided into high- and low-GNG4 groups. The biological function of GNG4 was annotated using Gene Ontology, gene set enrichment analysis, gene expression correlation analysis and immune infiltration analysis. Kaplan–Meier survival analysis was conducted and receiver operating characteristic (ROC) curves were calculated to determine the reliability of GNG4 in predicting prognostic significance and diagnostic value. Functional in vitro experiments were performed to explore the function of GNG4 in osteosarcoma cells. Results: GNG4 was generally highly expressed in osteosarcoma. As an independent risk factor, high GNG4 was negatively correlated with both overall survival and event-free survival. Furthermore, GNG4 was a good diagnostic marker for osteosarcoma, with an area under the receiver operating characteristic curve (AUC) of more than 0.9. Functional analysis suggested that GNG4 may promote the occurrence of osteosarcoma by regulating ossification, B-cell activation, the cell cycle and the proportion of memory B cells. In in vitro experiments, silencing of GNG4 inhibited the viability, proliferation and invasion of osteosarcoma cells. Conclusion: Through bioinformatics analysis and experimental verification, high expression of GNG4 in osteosarcoma was identified as an oncogene and reliable biomarker for poor prognosis. This study helps to elucidate the significant potential of GNG4 in carcinogenesis and molecular targeted therapy for osteosarcoma.

bioinformatics biomarker GNG4 osteosarcoma prognosis

SCI

英语

其他

WOS:000937466500001

2-s2.0-85148709655

Scopus

1.Department of Trauma Orthopedic and Hand Surgery,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi,China
2.Department of Orthopedic,The Affiliated Minzu Hospital of Guangxi Medical University,Nanning,Guangxi,China
3.Department of Spinal Bone Disease,The First Affiliated Hospital of Guangxi Medical University,Nanning,Guangxi,China
4.Department of Spinal Bone Disease,Yulin Orthopedics Hospital of Chinese and Western Medicine,Yulin,Guangxi,China
5.Department of Sports Medicine,Southern University of Science and Technology Hospital,Shenzhen,Guangdong,China
6.Department of Orthopaedics,the People’s Hospital of Baise,Baise,Guangxi,China

Jiang，Xiaohong,Tang，Fuxing,Zhang，Junlei,et al. High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification[J]. Frontiers in Oncology,2023,13.

Jiang，Xiaohong.,Tang，Fuxing.,Zhang，Junlei.,He，Mingwei.,Xie，Tianyu.,...&Wei，Qingjun.(2023).High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification.Frontiers in Oncology,13.

Jiang，Xiaohong,et al."High GNG4 predicts adverse prognosis for osteosarcoma: Bioinformatics prediction and experimental verification".Frontiers in Oncology 13(2023).