Osteosarcoma (OS) is an aggressive bone malignancy and the third most common cancer in adolescence. Since the late 1970s, OS therapy and prognosis had only modest improvements, making it appealing to explore new tools that could help ameliorate the treatment. We present a meta-analysis of the gene expression signature of primary OS, and propose small molecules that could reverse this signature. The meta-analysis was performed using GEO microarray series. We first compared gene expression from eleven primary OS against osteoblasts to obtain the differentially expressed genes (DEGs). We later filtered those DEGs by verifying which ones had a concordant direction of differential expression in a validation group of 82 OS samples versus 30 bone marrow mesenchymal stem cells (BM-MSC) samples. A final gene expression signature of 266 genes (98 up and 168 down regulated) was obtained. The L1000CDS² engine was used for drug repurposing. The top molecules predicted to reverse the signature were afatinib (PubChem CID 10184653), BRD-K95196255 (PubChem CID 3242434), DG-041 (PubChem CID 11296282) and CA-074 Me (PubChem CID 23760717). Afatinib (Gilotrif™) is currently used for metastatic non-small-cell lung cancer with EGFR mutations, and in vitro evidence shows antineoplastic potential in OS cells. The other three molecules have reports of antineoplastic effects, but are not currently FDA-approved. Further studies are necessary to establish the potential of these drugs in OS treatment. We believe our results can be an important contribution for the investigation of new therapeutic genetic targets and for selecting new drugs to be tested for OS.

骨肉瘤（OS）是一种侵袭性骨恶性肿瘤，是青春期第三大最常见的癌症。自1970年代后期以来，OS疗法和预后仅得到了适度的改善，因此寻求能够帮助改善治疗方法的新工具具有吸引力。我们提出了对主要操作系统的基因表达特征的荟萃分析，并提出了可以逆转该特征的小分子。使用GEO微阵列系列进行荟萃分析。我们首先比较了来自11个原发性OS与成骨细胞的基因表达，以获得差异表达的基因（DEG）。后来，我们通过验证在82个OS样本与30个骨髓间充质干细胞（BM-MSC）样本。获得了266个基因（98个上调和168个下调）的最终基因表达特征。L1000CDS ²引擎用于药物再利用。预计将逆转签名的最高分子是afatinib（PubChem CID 10184653），BRD-K95196255（PubChem CID 3242434），DG-041（PubChem CID 11296282）和CA-074 Me（PubChem CID 23760717）。阿法替尼（Gilotrif™）目前用于具有EGFR突变的转移性非小细胞肺癌，并在体外证据显示OS细胞具有抗肿瘤潜力。其他三种分子有抗肿瘤作用的报道，但目前尚未获得FDA批准。为了确定这些药物在OS治疗中的潜力，有必要进行进一步的研究。我们相信我们的结果可以为研究新的治疗性遗传靶标和选择要进行OS测试的新药做出重要贡献。