Osteosarcoma is the most common primary bone tumor in children and adolescents, and patients with advanced osteosarcoma with signs of metastasis have a poor prognosis . In order to identify new valuable prognostic biomarkers for OS, bioinformatics methods based on the GSE94805 dataset were used in this study.
Herein, the gene expression profiles of U2OS cells in the quiescence and senescence phases were analyzed, revealing 360 overlapping upregulated DEGs. However, these genes preliminarily screened were not necessarily related to the occurrence and development of OS. To further refine the study targets, String, Cytoscap, and MCODE plug-ins were used to conduct enrichment analysis, narrowing the investigation list to 113 key candidate genes. Next, 13 significantly upregulated genes were selected by comparing cancer and para-cancerous samples from OS patients. Furthermore, analysis with the Sangbox software showed that the expression of five closely related core genes – AURKB, EXO1, KIF4A, KIF15, and MCM4 – had significant impact on several survival and disease-progression prognostic indicators.
Aurora kinases (AURKs) are highly conserved serine/threonine kinases, including AURKA, AURKB, and AURKC, which are key regulators involved in mitosis . Studies have shown that AURKB is highly expressed in a variety of human cancers, such as lung , gastric  and liver  cancer, and is associated with tumor invasion and metastasis, and poor patient prognosis [13, 14]. Overexpression of AURKB can lead to errors during mitosis, such as damage to the junction between kinetochores and microtubules, interfering with chromosome concentration and spindle assembly, and hindering centromere localization, which can cause abnormal chromosome segregation and cytokinesis, ultimately leading to malignant cell transformation . AURKB inhibitors have no effect on non-proliferative cells and have little effect on normal cells . Therefore, AURKB holds potential as a clinical therapeutic target for tumors.
Exonuclease 1 (EXO1), a member of the Rad2/XPG nuclease family, plays important roles in the regulation of cell cycle checkpoint, replication fork maintenance, and DNA repair after replication . Previous studies revealed that EXO1 is associated with various cancers, including Lynch syndrome, ovarian, gastric, lung, breast, and pancreatic cancers . Overexpression of EXO1 disturbes the relative stability of the genome. Dai et al.  reported that EXO1 knockdown can reduce the proliferation of hepatocellular carcinoma cells in vitro, inhibit the survival of cancer clone cells, and is associated with poor prognosis of patients with hepatocellular carcinoma. To date, studies on EXO1 and OS are still lacking, and the role of EXO1 in OS is unclear. The present study suggests that high expression of EXO1 in OS is closely related to disease prognosis, and that the upregulation of EXO1 in OS might predict a poor clinical outcome.
The kinesin superfamily (KIFs) is a group of proteins that share highly conserved motor regions, including 1–14 subtypes. Most KIFs have ATP-dependent activity and catalyze microtubule-dependent tailing reactions. KIFs play important roles in the occurrence and development of tumors. KIF4A, a member of the kinesin-4 family, is located in the nucleus during the interphase, which is mainly involved in the biological processes of chromatin separation, spindle formation, and cytoplasmic separation during mitosis. KIF4A is abnormally expressed in lung and ovarian cancers, and oral squamous cell carcinoma . KIF15, belonging to the kinesin-12 family, is an N-rectified directional motor that plays a crucial role in the formation of bipolar spindles, and maintains the overall integrity of the spindle by shaping and stabilizing the kineto-fiber [21, 22]. Studies have shown that these proteins participate in several cellular processes, including proliferation, apoptosis, differentiation, and development .
MCM4 is a member of the minichromosome maintenance protein (MCM) with a highly conserved sequence. Commonly, MCM4 is active in the form of an MCM4/MCM6/MCM7 spherical trimer and MCM2–7cyclic hexamer . MCM2–7 proteins are present in proliferating cells. Cancers arising in different anatomic sites are also associated with MCM2, MCM4, and MCM6 overexpression [25, 26]. The MCM4 subunit is a target site for replication testing and is involved in DNA replication, assembly of related proteins, and regulation of the MCM4/MCM6/MCM7 helicase activity .