e collected two sets of GC patients with different races and socio-economic backgrounds to validate our findings. The specificity of the antibodies used 
26225771 was confirmed and optimized before being applied to the study. Double-blinded IHC scoring was used to reduce the observation and measurement bias. The multivariate and stratification analyses were conducted to reduce the confounder effects as much as possible. Another limitation was that we overexpressed RRM1 in AGS cells, but not in NCI-N87 cells. Further investigation is necessary to delineate the mechanism by which RRM1 promotes GC aggressiveness. In summary, we demonstrated that RRM1 overexpression was associated with poor prognosis in GC patients, especially advanced-stage GC. Also, RRM1 inhibition reduced proliferation and invasion in GC cells via the Ras/Raf/MAPK pathway. Therefore, RRM1 may be a potential prognostic and therapeutic biomarker in GC patients. Acknowledgments We thank Mrs. Mariko Lee from the Microscope core Lab, City of Hope, for technical assistance with acquisition of immunohistochemistry microscopy images; and Mrs. Yafan Wang from the Translational Medicine core Lab, City of Hope, for patients’ information collection in the City of Hope set, and Ms. Yanyan Chai from the Oncology Surgery 10646850 Dept, Sir Runrun Shaw Hospital, for patients’ information collection in Zhejiang University set. We also thank Mrs. Mansze Kong and Tony Yao helping with English edition. Innate immunity is the first line of defense used by the host against microbial infection. In human tissues, epithelial cells play a major role in innate immunity. Epithelial cells can not only form physical barriers, but also secrete inflammatory cytokines and chemokines in response to infection following recognition of microbial products by pattern-recognition receptors, such as Toll-like receptors and Nod-like receptors . The proinflammatory cytokines IL-1b and IL-18 have been linked to atherosclerosis, systemic inflammatory diseases, and autoimmune disease. Their expression and secretion are stringently controlled by pathogen-associated molecular patterns and danger signals. Some PAMPs like lipopolysaccharide, peptidoglycan, lipoteichoic acid, flagellin, and microbial nucleic acids induce pro-IL-1b and pro-IL-18 expression and intracellular accumulation. However, the maturation and secretion of these cytokines requires a danger signal like ATP or uric acid crystal, which comes from stressed or infected cell and leads to the activation of inflammasomes. Inflammasomes are large multiprotein complexes that act as a caspase-1-activating platform for IL-1b and IL-18 maturation. They can be categorized by the composition of their integral PRR family member, which acts as a scaffold protein that contributes to caspase-1 recruitment, clustering, and auto-activation. The best characterized inflammasome is the NLRP3 inflammasome. It contains NLRP3 as a scaffold protein, an apoptosisassociated speck-like protein containing a caspase recruitment domain MedChemExpress Peretinoin adaptor, and caspase-1. Danger-associated molecular patterns, such as extracellular ATP, can activate the NLRP3 inflammasome through ATP-gated P2X7 ion channels. Upon ATP stimulation, the P2X7 receptor opens a cation channel, which permits K+ efflux, and gradually forms a larger pore on the membrane by recruiting the hemichannel pannexin-1 to activate the NLRP3 inflammasome. Although P2X4 is also an ATP-gated ion channel, it has 1 P2X4 Modulates ATP-Induced Inflammasom