We have described the hitherto unrecognized potential of elevated expression levels of certain extracellular matrix (ECM) genes in brain tumor tissue to be of predictive value for the clinical course of the patient. High-ECM index patients exhibited a worse prognosis than low-ECM index patients. Four small molecules (podophyllotoxin, lasalocid, MG-262, and nystatin) that might reduce tumor development that putatively target the ECM candidates were predicted. Our prediction pipeline is available for use under https://ospg.shinyapps.io/OSPG/