3D Live Imaging and Transcriptome RNA Sequencing Analysis Show Lung Cancer Cell Death caused by IFNA2 Proteins
Abstract – Lung cancer is one of the most common and deadly cancers. In data analysis, we found that interferon alpha signaling genes were most significantly correlated with low patient survival rates. Interferon alpha 2 (IFN-alpha-2) has been used in monotherapy and combination therapy in other cancer types such as melanoma. Thus, its ability to inhibit cancer cell growth is evident; however, this study extends the use of IFN-alpha-2 to develop a novel treatment for lung cancer. The hypothetical benefits of supplementing IFN-alpha-2 in lung cancer patients were observed by analyzing the genomic data of lung cancer patients using a public web-based cBioportal genomic database. There was a positive correlation between patient groups with deep deleted IFNA genes and low survival rates, which led to the hypothesis that supplementing lung cancer cells with the IFN-alpha-2 protein could block cancer progression. Through 3D live-cell imaging technology, we confirmed that IFN-alpha-2 treatment induced cancer cell apoptosis. This study took a step further by using RNA sequencing technology to observe the impacts of IFN-alpha-2 on surrounding biological pathways. Downregulation results in particular showed that pathways related to transition metal ion homeostasis were affected the most. Also, our transcriptomic analysis suggested that the most likely side effects of IFN-alpha-2 treatment would be depression and oxidative stress caused by transition metal toxicity. Therefore, we suggested that vitamin E supplements may minimize these side effects. Overall, all evidence points to the conclusion that IFN-alpha-2 treatment is a viable candidate for novel lung cancer therapy.