Oxidative Stress and its Relation to Oncogenesis

Reactive oxygen species (ROS) activate multiple functions involved in cell cycle using cell signaling, leading to oxidative stress. The goal of this study was to identify how ROS drives oncogenesis in solid and liquid tumors and identify the essentiality of deregulated genes in different cancers. Through review of literature, 450 genes were identified to be associated with oxidative stress. By overlapping with multiple datasets, 24 genes were found to impact survival in solid and/or liquid tumors, becoming the ROS gene signature. Using PRECOG analysis, high expression of ROS generators was found to lead to poor survival, while low expression of antioxidant genes leads to poor survival. Because ROS genes are associated with poor survival in solid and liquid tumors, this indicates its role in oncogenesis. Expression of mitochondrial complex 1 genes also affect patient survival, as high expression of genes NDUFA9 and NDUFB11 leads to decreased survival in patients irrespective of cancer type. Through the DEPMAP CRISPR database, Complex 1 genes NDUFB9 and NDUFA11 and antioxidant genes PRDX2 and GPX4 were identified to be essential for liquid and solid tumors. ROS genes are essential in many tumors, indicating their vitality in growth and proliferation in cancer. Through DGIDB, COSMIC, and Clue, ROS gene SOD2 was found to be affected by drugs cyclophosphamide and methotrexate. Complex 1 gene NDUFB9 is affected by drugs metformin hydrochloride and NV-128, all known chemotherapy drugs. In conclusion, oxidative stress genes are essential in all types of cancer and can lead to improved cancer treatment options.